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1.
  • Aarne, Päivikki, et al. (author)
  • Parent-rated socio-emotional development in children with language impairment in comparison with typically developed children
  • 2014
  • In: European Journal of Developmental Psychology. - : Informa UK Limited. - 1740-5629 .- 1740-5610. ; 11:3, s. 279-291
  • Journal article (peer-reviewed)abstract
    • Children with language impairment (LI) and children with typical development (TD) were assessed by their respective parents using The MacArthur Communicative Development Inventories (Swedish version SECDI) and Greenspan Socio Emotional Growth Chart (GSEGC). The aim was to investigate socio-emotional and language development in children with LI and TD with respect to possible differential patterns and relations between the groups. The results highlight a clear association between language and socio-emotional development. Children with LI were rated similar to young language-matched children with TD, but significantly lower relative to age-matched TD children, particularly concerning symbolic stages of development: the use of linguistic symbols as well as related areas such as symbol play and symbolic mental ability. The results are discussed in light of presumable background factors and possible consequences for children or sub-groups of children with LI.
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2.
  • Almkvist, Ove, et al. (author)
  • A biomarker-validated time scale in years of disease progression has identified early- and late-onset subgroups in sporadic Alzheimer's disease
  • 2023
  • In: Alzheimer's Research & Therapy. - : Springer Nature. - 1758-9193. ; 15:1
  • Journal article (peer-reviewed)abstract
    • Background: It is possible to calculate the number of years to the expected clinical onset (YECO) of autosomal-dominant Alzheimer's disease (adAD). A similar time scale is lacking for sporadic Alzheimer's disease (sAD). The purpose was to design and validate a time scale in YECO for patients with sAD in relation to CSF and PET biomarkers. Methods: Patients diagnosed with Alzheimer's disease (AD, n = 48) or mild cognitive impairment (MCI, n = 46) participated in the study. They underwent a standardized clinical examination at the Memory clinic, Karolinska University Hospital, Stockholm, Sweden, which included present and previous medical history, laboratory screening, cognitive assessment, CSF biomarkers (A beta(42), total-tau, and p-tau), and an MRI of the brain. They were also assessed with two PET tracers, C-11-Pittsburgh compound B and F-18-fluorodeoxyglucose. Assuming concordance of cognitive decline in sAD and adAD, YECO for these patients was calculated using equations for the relationship between cognitive performance, YECO, and years of education in adAD (Almkvist et al. J Int Neuropsychol Soc 23:195-203, 2017). Results: The mean current point of disease progression was 3.2 years after the estimated clinical onset in patients with sAD and 3.4 years prior to the estimated clinical onset in patients with MCI, as indicated by the median YECO from five cognitive tests. The associations between YECO and biomarkers were significant, while those between chronological age and biomarkers were nonsignificant. The estimated disease onset (chronological age minus YECO) followed a bimodal distribution with frequency maxima before (early-onset) and after (late-onset) 65 years of age. The early- and late-onset subgroups differed significantly in biomarkers and cognition, but after control for YECO, this difference disappeared for all except the APOE e4 gene (more frequent in early- than in late-onset). Conclusions: A novel time scale in years of disease progression based on cognition was designed and validated in patients with AD using CSF and PET biomarkers. Two early- and late-disease onset subgroups were identified differing with respect to APOE e4.
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3.
  • Almkvist, Ove, et al. (author)
  • Cognitive decline from estimated premorbid status predicts neurodegeneration in Alzheimer's disease
  • 2009
  • In: Neuropsychology. - : American Psychological Association. - 0894-4105 .- 1931-1559. ; 23:1, s. 117-124
  • Journal article (peer-reviewed)abstract
    • This study investigated the relationship between premorbid and current cognitive function with respect to the clinical features of patients with various types of neurodegeneration in the form of Alzheimer's disease (AD), mild cognitive impairment (MCI), and subjective cognitive impairment (SCI), as compared with a healthy control group (C). Clinical features (MMSE, cognitive and depressive symptoms), genetics (apolipoprotein E; APOE) and measures of neurodegeneration (Aβ-sub(42), t-tau, and p-tau) were examined, as well as present cognitive function. Various methods of assessing premorbid cognitive function were compared, including a Swedish NART-analogous test (Irregularly Spelled Words; ISW), a Swedish lexical decision test (SLDT), a Hold test (Information in WAIS-R), Best current performance test, and combined demographic characteristics. Results showed that cognitive decline (premorbid minus current cognitive function) based on SLDT and ISW was a significant predictor for MMSE and Aβ-sub(42), whereas corresponding associations for present cognitive function and decline measures based on other methods were less powerful. Results also showed that specific verbal abilities (e.g., SLDT and ISW) were insensitive to AD and that these abilities indicated premorbid cognitive function in retrospect. In conclusion, cognitive decline from premorbid status reflects the disease processes.
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4.
  • Almkvist, Ove, et al. (author)
  • Degree of abnormality is associated with rate of change in measures of beta-amyloid, glucose metabolism and cognition in an autopsy-verified Alzheimer’s disease case
  • 2015
  • In: Neurocase. - : Informa UK Limited. - 1355-4794 .- 1465-3656. ; 21:6, s. 738-747
  • Journal article (peer-reviewed)abstract
    • The degree of abnormality and rate of change in cognitive functions, positron emission tomography Pittsburg compound B (PET PIB), and fluorodeoxyglucose (FDG) measures were studied for 8 years in an autopsy-confirmed Alzheimer’s disease (AD) patient, who died 61 years old (Mini-Mental State Examination (MMSE) score 7). At first encounter with medical care, the patient was very mildly demented (MMSE score 27). She had four cognitive assessments and two examinations with PET PIB and FDG in 23 bilateral brain regions. The onset of cognitive decline was retrospectively estimated to have started in the early forties. The degree of impairment was inversely related to the rate of decline. A similar relationship was seen between the rate of change and the level of abnormality in both PIB and FDG. To conclude, rate of change in cognition, PIB, and FDG was associated with the degree of abnormality.
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5.
  • Almkvist, Ove, et al. (author)
  • Estimation of premorbid cognitive function based on word knowledge : The Swedish Lexical Decision Test (SLDT)
  • 2007
  • In: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 48:3, s. 271-279
  • Journal article (peer-reviewed)abstract
    • In clinical neuropsychology, the present status of a patient is evaluated in relation to the assumed premorbid status. However, in Sweden, existing methods to assess premorbid status are far from optimal. In the present study, the design and evaluation of a Swedish Lexical Decision Test (SLDT) for premorbid global cognitive function (i.e., premorbid intelligence) is described. The design was based on the empirical finding that, in general adult population, word knowledge is strongly associated with measures of global cognitive functioning. Linear stepwise regression analysis demonstrated that SLDT findings accounted for 48% of the variance of global cognitive function as assessed by the Full Scale Intelligence Quotient (FSIQ) from the Wechsler Adult Intelligence Scale Revised (WAIS-R). Demographic variables alone accounted for 31% and a combination of SLDT results and demographics accounted for 60%. Psychometric properties are presented using data from 109 healthy individuals stratified according to age, gender, and level of education. In addition, a case of Alzheimer's disease is presented to illustrate the relationship between SLDT performance and cognitive function. Finally, the theoretical foundation for the relationship between word knowledge and global cognitive function is discussed.
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6.
  • Almkvist, Ove, et al. (author)
  • Longitudinal cognitive decline in autosomal-dominant Alzheimer's disease varies with mutations in APP and PSEN1 genes
  • 2019
  • In: Neurobiology of Aging. - : ELSEVIER SCIENCE INC. - 0197-4580 .- 1558-1497. ; 82, s. 40-47
  • Journal article (peer-reviewed)abstract
    • The purpose was to compare longitudinal cognitive changes in APP and PSEN1 gene mutation carriers and noncarriers from four autosomal-dominant Alzheimer's disease (ADAD) families across preclinical and early clinical stages of disease. Carriers (n = 34) with four different mutations (PSEN1(M146V), PSEN1(H163Y), APP(SWE), and APP(ARC)) and noncarriers (n = 41) were followed up longitudinally with repeated cognitive assessments starting many years before the expected clinical onset. The relationship between cognition and years to expected clinical onset, education, age, and type of mutation was analyzed using mixed-effects models. Results showed an education-dependent and time-related cognitive decline with linear and quadratic predictors in mutation carriers. Cognitive decline began close to the expected clinical onset and was relatively rapid afterward in PSEN1 mutation carriers, whereas decline was slower and started earlier than 10 years before expected clinical onset in APP mutation carriers. In noncarriers, the decline was minimal across time in accordance with normal aging. These results suggest that phenotypes for onset and rate of cognitive decline vary with PSEN1 and APP genes, suggesting a behavioral heterogeneity in ADAD. (C) 2019 Elsevier Inc. All rights reserved.
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7.
  • Almkvist, Ove, et al. (author)
  • Odor Identification Across Time in Mutation Carriers and Non-Carriers in Autosomal-Dominant Alzheimer’s Disease
  • 2024
  • In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 97:2, s. 587-598
  • Journal article (peer-reviewed)abstract
    • Background: Impaired odor identification is a characteristic of sporadic Alzheimer’sdisease(AD), but its presence in autosomal-dominantAD (adAD) remains uncertain. Objective: To investigate odor identification ability in mutation carriers (MC) and non-carriers (NC) of adAD in relation to years to estimated clinical onset clinical onset (YECO) of disease. Methods: Participants from six families with autosomal-dominant mutations (APP Swedish, APPArctic, and PSEN1 mutations) included 20 MC and 20 NC. The groups were comparable in age, gender, education, number of APOE ɛ4 alleles, and YECO, but differed in global cognition (Mini-Mental State Examination). The MC group included individuals in asymptomatic, symptomatic cognitively unimpaired, mild cognitive impairment, and dementia stages of disease, spanning approximately 40 years of the AD continuum. All NC were asymptomatic. Olfactory function was assessed by means of free and cued identification of common odors summarized as total identification. Results: MC performed poorer than NC in free and total identification. Four MC and none of the NC were anosmic. Olfactory functions in MC and NC were significantly and inversely related to time course (YECO) for both free and total identification. The decline in free identification began approximately 10 years prior to the estimated clinical onset of AD in MC. Odor identification proficiency was associated with episodic memory and executive function in MC and NC. Conclusions: Impaired odor identification is present well before the clinical diagnosis of AD in MC and is associated with disease progression. Odor identification ability may be a useful early biomarker for adAD.
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8.
  • Almkvist, Ove, et al. (author)
  • Practice effects in cognitive assessments three years later in non-carriers but not in symptom-free mutation carriers of autosomal-dominant Alzheimer's disease : Exemplifying procedural learning and memory?
  • 2022
  • In: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 14
  • Journal article (peer-reviewed)abstract
    • Practice effects (PEs) defined as an improvement of performance in cognition due to repeated assessments between sessions are well known in unimpaired individuals, while less is known about impaired cognition and particularly in latent brain disease as autosomal-dominant Alzheimer's disease. The purpose was to evaluate the general (across tests/domains) and domain-specific PE calculated as the annual rate of change (ARC) in relation to years to the estimated disease onset (YECO) and in four groups of AD: asymptomatic mutation carriers (aAD, n = 19), prodromal, i.e., symptomatic mutation carriers, criteria for AD diagnosis not fulfilled (pAD, n = 4) and mutation carriers diagnosed with AD (dAD, n = 6) as well as mutation non-carriers from the AD families serving as a healthy comparison group (HC, n = 35). Cognition was assessed at baseline and follow-up about 3 years later by 12 tests covering six domains. The aAD and HC groups were comparable at baseline in demographic characteristics (age, gender, and education), when they were in their early forties, while the pAD and dAD groups were older and cognitively impaired. The results on mean ARC for the four groups were significantly different, small, positive, and age-insensitive in the HC group, while ARC was negative and declined with time/disease advancement in AD. The differences between HC and aAD groups in mean ARC and domain-specific ARC were not significant, indicating a subtle PE in aAD in the early preclinical stage of AD. In the symptomatic stages of AD, there was no PE probably due to cognitive disease-related progression. PEs were the largest in the verbal domain in both the HC and aAD groups, indicating a relationship with cognitive vulnerability. The group-related difference in mean ARC was predominant in timekeeping tests. To conclude, the practice effect in over 3 years was suggested to be linked to procedural learning and memory.
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9.
  • Almkvist, Ove, et al. (author)
  • Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease
  • 2017
  • In: Journal of the International Neuropsychological Society. - : CAMBRIDGE UNIV PRESS. - 1355-6177 .- 1469-7661. ; 23:3, s. 195-203
  • Journal article (peer-reviewed)abstract
    • Objectives: The aim of this study was to investigate cognitive performance including preclinical and clinical disease course in carriers and non-carriers of autosomal-dominant Alzheimer's disease (adAD) in relation to multiple predictors, that is, linear and non-linear estimates of years to expected clinical onset of disease, years of education and age. Methods: Participants from five families with early-onset autosomal-dominant mutations (Swedish and Arctic APP, PSEN1 M146V, H163Y, and I143T) included 35 carriers (28 without dementia and 7 with) and 44 non-carriers. All participants underwent a comprehensive clinical evaluation, including neuropsychological assessment at the Memory Clinic, Karolinska University Hospital at Huddinge, Stockholm, Sweden. The time span of disease course covered four decades of the preclinical and clinical stages of dementia. Neuropsychological tests were used to assess premorbid and current global cognition, verbal and visuospatial functions, short-term and episodic memory, attention, and executive function. Results: In carriers, the time-related curvilinear trajectory of cognitive function across disease stages was best fitted to a formulae with three predictors: years to expected clinical onset (linear and curvilinear components), and years of education. In non-carriers, the change was minimal and best predicted by two predictors: education and age. The trajectories for carriers and non-carriers began to diverge approximately 10 years before the expected clinical onset in episodic memory, executive function, and visuospatial function. Conclusions: The curvilinear trajectory of cognitive functions across disease stages was mimicked by three predictors in carriers. In episodic memory, executive and visuospatial functions, the point of diverging trajectories occurred approximately 10 years ahead of the clinical onset compared to non-carriers.
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10.
  • Almkvist, Ove, et al. (author)
  • Selective impact of disease on short-term and long-term components of self-reported memory : a population-based HUNT study
  • 2017
  • In: BMJ Open. - : BMJ. - 2044-6055. ; 7:5
  • Journal article (peer-reviewed)abstract
    • Background: Subjective memory is commonly considered to be a unidimensional measure. However, theories of performance-based memory suggest that subjective memory could be divided into more than one dimension. Objective: To divide subjective memory into theoretically related components of memory and explore the relationship to disease. Methods: In this study, various aspects of self-reported memory were studied with respect to demographics and diseases in the third wave of the HUNT epidemiological study in middle Norway. The study included all individuals 55 years of age or older, who responded to a nine-item questionnaire on subjective memory and questionnaires on health (n=18 633). Results: A principle component analysis of the memory items resulted in two memory components; the criterion used was an eigenvalue above 1, which accounted for 54% of the total variance. The components were interpreted as long-term memory (LTM; the first component; 43% of the total variance) and short-term memory (STM; the second component; 11% of the total variance). Memory impairment was significantly related to all diseases (except Bechterew's disease), most strongly to brain infarction, heart failure, diabetes, cancer, chronic obstructive pulmonary disease and whiplash. For most diseases, the STM component was more affected than the LTM component; however, in cancer, the opposite pattern was seen. Conclusions: Subjective memory impairment as measured in HUNT contained two components, which were differentially associated with diseases.
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11.
  • Almkvist, Ove, et al. (author)
  • Subcortical and Cortical Regions of Amyloid-β Pathology Measured by C-11-PiB PET Are Differentially Associated with Cognitive Functions and Stages of Disease in Memory Clinic Patients
  • 2021
  • In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 81:4, s. 1613-1624
  • Journal article (peer-reviewed)abstract
    • Background: The effect of regional brain amyloid-beta (A beta) pathology on specific cognitive functions is incompletely known.Objective: The relationship between A beta and cognitive functions was investigated in this cross-sectional multicenter study of memory clinic patients.Methods: The participants were patients diagnosed with Alzheimer's disease (AD, n = 83), mild cognitive impairment (MCI, n = 60), and healthy controls (HC, n = 32), who had been scanned by C-11-PiB PET in 13 brain regions of both hemispheres and who had been assessed by cognitive tests covering seven domains.Results: Hierarchic multiple regression analyses were performed on each cognitive test as dependent variable, controlling for demographic characteristics and APOE status (block 1) and PiB measures in 13 brain regions (block 2) as independent variables. The model was highly significant for each cognitive test and most strongly for tests of episodic memory (learning and retention) versus PiB in putamen, visuospatially demanding tests (processing and retention) versus the occipital lobe, semantic fluency versus the parietal lobe, attention versus posterior gyrus cinguli, and executive function versus nucleus accumbens. In addition, education had a positively and APOE status a negatively significant effect on cognitive tests.Conclusion: Five subcortical and cortical regions with A beta pathology are differentially associated with cognitive functions and stages of disease in memory clinic patients.
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12.
  • Almkvist, Ove, et al. (author)
  • Subjective working and declarative memory in dementia and normal aging
  • 2019
  • In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 140:2, s. 140-146
  • Journal article (peer-reviewed)abstract
    • Objective: Subjective memory complaints are common in both elderly individuals and patients with dementia. This study investigated the power of subjective memory, divided into declarative and working memory, to differentiate between patients with dementia and normal elderly individuals.Method: Two groups of participants, patients with dementia (n = 117) and normal elderly individuals (n = 117), individually matched with regard to age, gender, and education. All subjects had participated in the third wave of the HUNT population health survey in Nord-Trondelag County in Norway and completed the Meta-Memory Questionnaire (MMQ) in the HUNT study. The MMQ was subdivided into two components, one associated with declarative memory (episodic and semantic) and the other with working memory.Results: Patients with dementia reported significantly more subjective memory concerns than normal elderly individuals. The difference between working and declarative memory components was significantly greater in patients with dementia than in normal elderly individuals. This finding made it possible to differentiate patients with dementia from the normal elderly individuals. Mental and somatic health conditions did not significantly add power to differentiating the two groups.Conclusion: In clinical and research applications, subjective memory components could contribute to differentiation of patients with dementia and normal elderly individuals by using self-reported impairment in working memory, rather than declarative memory.
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13.
  • Almkvist, Ove, et al. (author)
  • The APOE ε4 Allele Affects Cognitive Functions Differently in Carriers of APP Mutations Compared to Carriers of PSEN1 Mutations in Autosomal-Dominant Alzheimer’s Disease
  • 2021
  • In: Genes. - : MDPI AG. - 2073-4425. ; 12:12
  • Journal article (peer-reviewed)abstract
    • Mounting evidence shows that the APOE ε4 allele interferes with cognition in sporadic Alzheimer’s disease. Less is known about APOE in autosomal-dominant Alzheimer’s disease (adAD). The present study explored the effects on cognition associated with the gene–gene interactions between the APOE gene and the APP and PSEN1 genes in adAD. This study includes mutation carriers (MC) and non-carriers (NC) from adAD families with mutations in APP (n = 28 and n = 25; MC and NC, respectively) and PSEN1 (n = 12 and n = 15; MC and NC, respectively) that represent the complete spectrum of disease: AD dementia (n = 8) and mild cognitive impairment (MCI, n = 15 and presymptomatic AD, n = 17). NC represented unimpaired normal aging. There was no significant difference in the distribution of APOE ε4 (absence vs. presence) between the APP vs. PSEN1 adAD genes and mutation status (MC vs. NC). However, episodic memory was significantly affected by the interaction between APOE and the APP vs. PSEN1 genes in MC. This was explained by favorable performance in the absence of APOE ε4 in PSEN1 compared to APP MC. Similar trends were seen in other cognitive functions. No significant associations between APOE ε4 and cognitive performance were obtained in NC. In conclusion, cognitive effects of APOE–adAD gene interaction were differentiated between the PSEN1 and APP mutation carriers, indicating epistasis.
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15.
  • Andersson, Christin, et al. (author)
  • Differential CSF biomarker levels in APOE-epsilon4-positive and -negative patients with memory impairment.
  • 2007
  • In: Dementia and geriatric cognitive disorders. - Basel : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:2, s. 87-95
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To investigate the relationships between episodic memory, APOE genotype, CSF markers (total tau, T-tau; phospho-tau, P-tau; beta-amyloid, Abeta42) and longitudinal cognitive decline. METHODS: 124 memory clinic patients were retrospectively divided into 6 groups based on (i) episodic memory function (Rey Auditory Verbal Learning Test, RAVLT): severe, moderate or no impairment (SIM, MIM or NIM), and (ii) APOE genotype (epsilon4+ or epsilon4-). CSF marker levels and cognitive decline were compared across groups. RESULTS: Episodic memory function, according to RAVLT scores, was significantly correlated with CSF marker levels only among epsilon4+ subjects and not among epsilon4- subjects. When comparing the 6 subgroups, SIM epsilon4+ and MIM epsilon4+ groups showed significantly lower Abeta42 levels than the other groups. T-tau and P-tau levels were significantly increased in SIM epsilon4+ when compared to all the other groups, including the SIM epsilon4- group. However, both SIM epsilon4+ and SIM epsilon4- declined cognitively during the follow-up. CONCLUSION: It remains to be determined whether APOE genotype affects the expression of biomarkers in CSF, or whether the different biomarker patterns reflect different types of disease processes in patients with progressive cognitive dysfunction.
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16.
  • Andersson, Christin, et al. (author)
  • Identifying patients at high and low risk of cognitive decline using Rey Auditory Verbal Learning Test among middle-aged memory clinic outpatients
  • 2006
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 21:4, s. 251-259
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To investigate whether application of cutoff levels in an episodic memory test (Rey Auditory Verbal Learning Test, RAVLT) is a useful method for identifying patients at high and low risk of cognitive decline and subsequent dementia. METHODS: 224 patients with memory complaints (mean age = 60.7 years, mean MMSE = 28.2) followed-up at a memory clinic over approximately 3 years were assigned retrospectively to one of three memory groups from their baseline results in RAVLT [severe (SIM), moderate (MIM) or no impairment (NIM)]. These groups were investigated regarding cognitive decline. RESULTS: Patients assigned to SIM showed significant cognitive decline and progressed to dementia at a high rate, while a normal performance in RAVLT at baseline (NIM) predicted normal cognition after 3 years. Patients with MIM constituted a heterogeneous group; some patients deteriorated cognitively, while the majority remained stable or improved. CONCLUSIONS: The application of cutoff levels in RAVLT at baseline showed that patients with severely impaired RAVLT performance were at a high risk of cognitive decline and progression to dementia, while patients with normal RAVLT results did not show cognitive decline during 3 years. Furthermore, the initial degree of memory impairment was decisive in the cognitive prognosis 3 years later.
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17.
  • Andersson, Christin, et al. (author)
  • Increasing CSF phospho-tau levels during cognitive decline and progression to dementia
  • 2008
  • In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:10, s. 1466-1473
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression. OBJECTIVE: To investigate longitudinal changes in CSF biomarkers--total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during cognitive decline. METHODS: Forty memory clinic patients (47.5% females), aged 61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/-1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM). RESULTS: There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Abeta42-levels did not change in any of the memory groups during follow-up. CONCLUSION: Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.
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18.
  • Ausén, Birgitta, et al. (author)
  • Personality Features in Subjective Cognitive Impairment and Mild Cognitive Impairment - Early Indicators of Dementia?
  • 2009
  • In: Dementia and Geriatric Cognitive Disorders. - Basel : Karger AG. - 1420-8008 .- 1421-9824. ; 28:6, s. 528-535
  • Journal article (peer-reviewed)abstract
    • Objectives: The purpose of the present study was to investigate patterns of personality in patients with subjective cognitive impairment (SCI) and mild cognitive impairment (MCI), compared to healthy controls. Methods: We assessed24 patients with SCI, 35 patients with MCI and 26 healthy controls with the self-report questionnaire Swedish Universities Scales of Personality measuring aspects of neuroticism/anxiety proneness, extraversion, and aggression-hostility. Results: Patients with SCI and MCI showed significantly more Somatic Trait Anxiety, Psychic Trait Anxiety and Stress Susceptibility than healthy controls. Moreover, there was a significant increase in Detachment in patients with MCI and a significant decrease in Adventure Seeking in patients with SCI, relative to healthy controls. Conclusions: Patients with SCI and MCI presented specific patterns of personality alterations with higher scores in traits related to anxiety proneness and aggression-hostility and lower in traits of extraversion. In most subscales differences followed a sequential pattern with gradually increasing scores from healthy controls, to patients with SCI and further to MCI. The groups differed in amount and type of symptoms, suggesting that patterns of personality may be related to degree of cognitive impairment.
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19.
  • Ausen, Birgitta, et al. (author)
  • Self- and Informant Ratings of Personality in Mild Cognitive Impairment, Reviewed
  • 2011
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 32:6, s. 387-393
  • Journal article (peer-reviewed)abstract
    • Aims: To examine the degree of agreement between self-and informant ratings of personality in relation to cognitive function in patients with mild cognitive impairment (MCI), subjective cognitive impairment (SCI) and healthy controls (HC). Methods: Thirty-two patients and informants with MCI, 23 with SCI and 22 HC completed the Swedish universities Scales of Personality (SSP). Correlations and incongruence between self-and informant ratings were calculated. The Mini Mental State Examination (MMSE) was used to assess cognitive function. Results: The correlations between self-and and informant ratings were fair-to-moderate on a majority of SSP scales and significant in 44%. The incongruence between patients and informants was significantly larger in MCI than in HC across SSP scales. There was a significant negative correlation between the incongruence index and the MMSE for all subjects. Conclusions: Self-informant agreement on ratings of patients' personality was reasonable. Incongruence between patients and their informants was associated with MCI but not SCI or HC. Disagreement between patients and informants indicates cognitive impairment. Copyright (C) 2012 S. Karger AG, Basel
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21.
  • Basun, Hans, et al. (author)
  • Clinical and neuropathological features of the arctic APP gene mutation causing early-onset Alzheimer disease
  • 2008
  • In: Archives of neurology. - : American Medical Association (AMA). - 0003-9942 .- 1538-3687. ; 65:4, s. 499-505
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: A majority of mutations within the beta-amyloid region of the amyloid precursor protein (APP) gene cause inherited forms of intracerebral hemorrhage. Most of these mutations may also cause cognitive impairment, but the Arctic APP mutation is the only known intra-beta-amyloid mutation to date causing the more typical clinical picture of Alzheimer disease. OBJECTIVE: To describe features of 1 Swedish and 1 American family with the previously reported Arctic APP mutation. DESIGN, SETTING, AND PARTICIPANTS: Affected and nonaffected carriers of the Arctic APP mutation from the Swedish and American families were investigated clinically. In addition, 1 brain from each family was investigated neuropathologically. RESULTS: The clinical picture, with age at disease onset in the sixth to seventh decade of life and dysfunction in multiple cognitive areas, is indicative of Alzheimer disease and similar to the phenotype for other Alzheimer disease APP mutations. Several affected mutation carriers displayed general brain atrophy and reduced blood flow of the parietal lobe as demonstrated by magnetic resonance imaging and single-photon emission computed tomography. One Swedish case and 1 American case with the Arctic APP mutation came to autopsy, and both showed no signs of hemorrhage but revealed severe congophilic angiopathy, region-specific neurofibrillary tangle pathological findings, and abundant amyloid plaques. Intriguingly, most plaques from both of these cases had a characteristic ringlike character. CONCLUSIONS: Overall, our findings corroborate that the Arctic APP mutation causes a clinical and neuropathological picture compatible with Alzheimer disease.
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22.
  • Bergendal, G., et al. (author)
  • Callosal atrophy in multiple sclerosis is related to cognitive speed
  • 2013
  • In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 19:7, s. 969-969
  • Journal article (peer-reviewed)abstract
    • Bergendal G, Martola J, Stawiarz L, Kristoffersen-Wiberg M, Fredrikson S, Almkvist O. Callosal atrophy in multiple sclerosis is related to cognitive speed. Acta Neurol Scand: 2013: 127: 281-289. (C) 2012 John Wiley & Sons A/S. Background Long-term changes regarding corpus callosum area (CCA) and information processing speed in cognitive and sensory-motor tasks have rarely been studied in multiple sclerosis (MS). Objective and methods Information processing speed in cognitive (Symbol Digit Modalities Test, SDMT), sensory (visual and auditory reaction time) and motor (finger-tapping speed, FT; right and left hand) tasks as well as auditory inter-hemispheric transfer (verbal dichotic listening, VDL) was related to CCA, measured by MRI at baseline and at follow-up after nine years in 22 patients with MS. Possible confounding by demographic (age, gender and education), clinical (symptom onset, duration, severity of disease) and relative brain volume (RBV) as well as T2 lesion load was taken into account. Results The smaller the CCA at baseline, the slower was SDMT performance at baseline. In a similar way, CCA at follow-up was associated with poor SDMT result at follow-up. Furthermore, the higher the annual rate of change in CCA, the poorer was performance in VDL on the left ear and the more pronounced was the right ear advantage. A positive relationship between performance in VDL right ear and annual rate of change in RBV was also seen. Sensory-motor tests were not significantly associated with CCA. T2 lesion load at baseline was associated with FT performance at baseline. Demographic, clinical and radiological (RBV and T2 lesion load) characteristics did not confound the significant relation between CCA and SDMT. Conclusions CCA unlike RBV and T2 lesion load was associated with SDMT, which indicated a marked cognitive rather than perceptual-motor component.
  •  
23.
  • Bergendal, G., et al. (author)
  • Selective decline in information processing in subgroups of multiple sclerosis : An 8-year longitudinal study
  • 2007
  • In: European Neurology. - : S. Karger AG. - 0014-3022 .- 1421-9913. ; 57:4, s. 193-202
  • Journal article (peer-reviewed)abstract
    • Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system (CNS) that causes white matter and cortical lesions over many years. The CNS is selectively affected by the disease with a great variety of symptoms between patients. In this study, we describe the impact on various aspects of cognition over an 8-year follow-up period in 31 consecutive MS patients subgrouped as relapsing remitting (RR) MS, secondary progressive (SP) MS, and primary progressive (PP) MS. Results showed a differential pattern of cognitive decline already at baseline in speed of information processing. During the follow-up, a pronounced decline occurred in speed of information processing, finger-motor speed, copying geometrical designs, episodic memory, and visuospatial short-term memory. A striking difference was observed between a marked decline in visual reaction time, whereas no significant change was seen in auditory reaction time. In contrast, there was no time-related decline in verbal abilities. However, an initial marked cognitive impairment predicted further cognitive decline over the 8-year follow-up. Information-processing tests were found to be an especially strong predictor of long-term cognitive decline. In addition, high EDSS score at followup was associated with decline in information processes. Results also showed that SP-MS patients deteriorated significantly more than the other two groups, particularly in visual compared to auditory information processing. To conclude, cognitive decline appeared particularly in SP-MS patients and in visual information processing.
  •  
24.
  • Bergman, Ingvar, et al. (author)
  • Health-adjusted neuropsychological test norms based on 463 older Swedish car drivers
  • 2016
  • In: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 57:2, s. 93-107
  • Journal article (peer-reviewed)abstract
    • There is a need for improved normative information in particular for older persons. The present study provides neuropsychological test norms on seven cognitive tests used in a sample representing the general older driving population, when uncontrolled and controlled for physical health. A group of 463 healthy Swedish car drivers, aged 65 to 84 years, participated in a medical and neuropsychological examination. The latter included tests of visual scanning, mental shifting, visual spatial function, memory, reaction time, selective attention, and simultaneous capacity. Hierarchical regression analyses demonstrated that, when uncontrolled for health, old age was associated with significant impairment on all seven tests. Education was associated with a significant advantage for all tests except most reaction time subtests. Women outperformed men on selective attention. Controlling for health did not consistently change the associations with education, but generally weakened those with age, indicating rises in normative scores of up to 0.36 SD (residual). In terms of variance explained, impaired health predicted on average 2.5%, age 2.9%, education 2.1% and gender 0.1%. It was concluded (1)that individual regression-based predictions of expected values have the advantage of allowing control for the impact of health on normative scores in addition to the adjustment for various demographic and performance-related variables and (2) that health-adjusted norms have the potential to classify functional status more accurately, to the extent that these norms diverge from norms uncontrolled for physical health.
  •  
25.
  • Bergman, Ingvar, et al. (author)
  • Neuropsychological test norms controlled for physical health : Does it matter?
  • 2015
  • In: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 56:2, s. 140-150
  • Journal article (peer-reviewed)abstract
    • The objective of the present study was to investigate the effects of physical health on neuropsychological test norms. Medical and neuropsychological data from 118 healthy volunteer controls, aged 26-91years, were collected during five recruitment occasions. The examinations included a clinical investigation, brain neuroimaging, and a comprehensive neuropsychological test battery. Test-specific statistical regression-weights for age, education and gender were calculated to establish preliminary test norms. Hierarchical regression analyses demonstrated that control in addition for physical health moved best performance from age 60 to 65 for abstraction; replaced a plateau above age 70 for verbal fluency, with a continued rise in performance; eliminated significant negative influences of age on auditory learning, spatial reasoning and complex copying; reduced them on wordlist recall, psychomotor speed, visual scanning and mental shifting; and slightly reduced negative influences of low education on most verbal tests, several memory tests, and psychomotor speed, indicating rises in normative scores of up to 0.8 SD at age 80 and 0.4 SD at age 60. No differences were found at age 40. Although the sample size is not adequate to be used for normative data, the findings indicate that norms uncontrolled for health overestimate the negative influence of advanced age and low education, implying a risk of drawing false diagnostic conclusions.
  •  
26.
  • Bergman, Ingvar, et al. (author)
  • The effect of age on fluid intelligence is fully mediated by physical health
  • 2013
  • In: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 57:1, s. 100-109
  • Journal article (peer-reviewed)abstract
    • The present study investigated the extent to which the effect of age on cognitive ability is predicted by individual differences in physical health. The sample consisted of 118 volunteer subjects who were healthy and ranging in age from 26 to 91. The examinations included a clinical investigation, magnetic resonance imaging (MRI) brain neuroimaging, and a comprehensive neuropsychological assessment. The effect of age on fluid IQ with and without visual spatial praxis and on crystallized IQ was tested whether being fully-, partially-or non-mediated by physical health. Structural equation analyses showed that the best and most parsimonious fit to the data was provided by models that were fully mediated for fluid IQ without praxis, non-mediated for crystallized IQ and partially mediated for fluid IQ with praxis. The diseases of the circulatory and nervous systems were the major mediators. It was concluded from the pattern of findings that the effect of age on fluid intelligence is fully mediated by physical health, while crystallized intelligence is non-mediated and visual spatial praxis is partially mediated, influenced mainly by direct effects of age. Our findings imply that improving health by acting against the common age-related circulatory-and nervous system diseases and risk factors will oppose the decline in fluid intelligence with age.
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27.
  • Bergman, Ingvar, et al. (author)
  • The importance of impaired physical health and age in normal cognitive aging
  • 2007
  • In: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 48:2, s. 115-125
  • Journal article (peer-reviewed)abstract
    • The objective of this study was to investigate the importance of impaired physical health and age in normal cognitive aging. In our cross-sectional, clinical and explorative study, medical and neuropsychological data from 118 voluntary healthy controls aged 26-91 years were collected from five recruitment occasions. Health was assessed according to a criterion reflecting clinical and subclinical severity. The examinations included a clinical investigation, brain neuroimaging, and a comprehensive neuropsychological assessment. Regression analyses showed a significant incidence of clinical and subclinical medical disorders that explained 10.8% of the variation in cognitive performance, while age-related impairment explained 5.6%. Findings of the central nervous system were important but various other medical findings explained about half of the health-related variation. Cognitively demanding tasks were more susceptible to impaired physical health while tasks comprising salient motor- and visual spatial elements were more prone to be impaired by age. Our findings suggest (1) that impaired physical health is more important than chronological age in accounting for cognitive impairment across the adult lifespan, (2) that age and health dissociate with regard to cognitive functions affected, and (3) that selection for so-called ""super healthy"" elderly people might be justified in cognitive research. Because the prevalent diseases in normal aging are potentially preventable, the present findings promise good prospect for prevention of future cognitive disability among elderly people.
  •  
28.
  • Bosnes, Ingunn, et al. (author)
  • Lifestyle predictors of successful aging : A 20-year prospective HUNT study
  • 2019
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:7
  • Journal article (peer-reviewed)abstract
    • Background Lifestyle factors predicting successful aging as a unified concept or as separate components of successful aging are important for understanding healthy aging, interventions and preventions. The main objective was to investigate the effect of midlife predictors on subsequent successful aging 20 years later. Materials and methods Data were from a population-based health survey, the Nord-Trondelag Health Study (HUNT), with an average follow-up of 22.6 years. Individuals free of major disease at baseline in 1984-86 with complete datasets for the successful aging components in HUNT3 in 2006-08, were included (n = 4497; mean age at baseline 52.7, range 45-59, years). Successful aging was defined either as a unified category or as three components: being free of nine specified diseases and depression, having no physical or cognitive impairment, and being actively engaged with life. The midlife predictors (smoking, physical activity, alcohol consumption, obesity and social support) were analysed both as separate predictors and combined into a lifestyle index controlling for sociodemographic variables, using multivariable regression analysis. Results Successful aging as a unified concept was related to all the lifestyle factors in the unadjusted analyses, and all except alcohol consumption in the adjusted analyses. The individual components of successful aging were differently associated with the lifestyle factors; engagement with life was less associated with the lifestyle factors. Non-smoking and good social support were the most powerful predictors for successful aging as a unified concept. When the lifestyle factors were summed into a lifestyle index, there was a trend for more positive lifestyle to be related to higher odds for successful aging. Conclusions Lifestyle factors predicted an overall measure of SA, as well as the individual components, more than 20 years later. Modifiable risk factors in midlife, exemplified by social support, may be used for interventions to promote overall health and specific aspects of health in aging.
  •  
29.
  • Bosnes, Ingunn, et al. (author)
  • Prevalence and correlates of successful aging in a population-based sample of older adults : the HUNT study
  • 2017
  • In: International psychogeriatrics. - 1041-6102 .- 1741-203X. ; 29:3, s. 431-440
  • Journal article (peer-reviewed)abstract
    • The factors influencing successful aging (SA) are of great interest in an aging society. The aims of this study were to investigate the prevalence of SA, the relative importance across age of the three components used to define it (absence of disease and disability, high cognitive and physical function, and active engagement with life), and its correlates. Data were extracted from the population-based cross-sectional Nord-Trøndelag Health Study (HUNT3 2006–2008). Individuals aged 70–89 years with complete datasets for the three components were included (N = 5773 of 8,040, 71.8%). Of the respondents, 54.6% were women. Univariate and multivariate regression analyses were used to analyze possible correlates of SA. Overall, 35.6% of the sample met one of the three criteria, 34.1% met combinations, and 14.5% met all of the three criteria. The most demanding criterion was high function, closely followed by absence of disease, while approximately two-thirds were actively engaged in life. The relative change with age was largest for the high cognitive and physical function component and smallest for active engagement with life. The significant correlates of SA were younger age, female gender, higher education, weekly exercise, more satisfaction with life, non-smoking, and alcohol consumption, whereas marital status was not related to SA. The prevalence of SA in this study (14.5%) is comparable to previous studies. It may be possible to increase the prevalence by intervention directed toward more exercise, non-smoking, and better satisfaction with life.
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30.
  • Bosnes, Ingunn, et al. (author)
  • Processing speed and working memory are predicted by components of successful aging : a HUNT study
  • 2022
  • In: BMC Psychology. - : Springer Science and Business Media LLC. - 2050-7283. ; 10:1
  • Journal article (peer-reviewed)abstract
    • Background: Research has demonstrated that cognitive heterogeneity occurs with aging both within and between individuals. The purpose of this study was to explore whether the cognitive heterogeneity in aging was related to the subgroups of successful and usual aging.Method: Participants were a representative sample of normal older adults (n = 65, age range 70–89 years). All subjects had participated in the third phase of the Nord-Trøndelag Health Survey (HUNT3) and completed all subtests in the Wechsler Memory Scale (WMS-III) and Wechsler Adult Intelligence Scale (WAIS-III). Successful aging was defined in four ways in the study: as (1) absence of disease, (2) high functioning, (3) active engagement with life, or (4) all three components combined. Five domains of memory and intelligence functions were investigated using linear regression analysis, with group membership (successful versus usual aging) as predictors and age, sex and education as correlates.Results: Processing speed performance was correlated with the successful aging component absence of disease, younger age and being of the female sex, while working memory performance was correlated with the successful aging component absence of disease and more years of education. Performance in other domains (verbal, visuospatial, and episodic memory) were not related to any successful aging definition. Age had a consistent negative effect on the processing speed domain for all successful aging definitions. Education was positively linked to cognitive performance on the verbal and working memory domains. Being female was positively linked to processing speed and episodic memory.Conclusions: Processing speed and working memory were linked to successful aging when it was defined as absence of disease, but not by other components of successful aging, i.e. domain-specific. In contrast, other cognitive domains were not related to any components of successful aging.
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31.
  • Bosnes, O., et al. (author)
  • Including a subject-paced trial may make the PASAT more acceptable for MS patients
  • 2015
  • In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 132:4, s. 219-225
  • Journal article (peer-reviewed)abstract
    • The Paced Auditory Serial Addition Test (PASAT) is regularly used in the evaluation of cognition in multiple sclerosis (MS). However, the test may impose frustration, distress, and anxiety in patients, which may result in refusal to participate by many patients. ObjectivesIn this study, a subject- and experimenter-paced PASAT was compared and analyzed, with regard to independent measures of cognitive functions, as well as disability, fatigue, depression, and anxiety. MethodsA population-based sample of patients with MS (n=34; mean age 47.28.6) was examined with the PASAT, including a subject-paced condition, in addition to the standard experimenter-paced conditions using three levels of interstimuli intervals (ISI: 3.0, 2.5, and 2.0s). A comprehensive set of neuropsychological tests, measures of disease severity, fatigue, anxiety, and depression were studied as potentially associated factors. ResultsSubject- and experimenter-paced PASAT performance correlated significantly and the subject-paced administration correlated even higher with measures of information processing speed, executive function, attention, and working memory than standard experimenter-paced administration of PASAT. DiscussionThe associations between PASAT performance and measures of fatigue, anxiety, and depression were not significant. ConclusionThe results indicate that the altered PASAT procedure measures the same cognitive functions in MS as the standard procedure. At the same time, the altered procedure may make the PASAT more user-friendly for patients with MS.
  •  
32.
  • Carter, Stephen F., et al. (author)
  • Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by C-11-Deuterium-L-Deprenyl : A Multitracer PET Paradigm Combining C-11-Pittsburgh Compound B and F-18-FDG
  • 2012
  • In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 53:1, s. 37-46
  • Journal article (peer-reviewed)abstract
    • Astrocytes colocalize with fibrillar amyloid-beta (A beta) plaques in postmortem Alzheimer disease (AD) brain tissue. It is therefore of great interest to develop a PET tracer for visualizing astrocytes in vivo, enabling the study of the regional distribution of both astrocytes and fibrillar A beta. A multitracer PET investigation was conducted for patients with mild cognitive impairment (MCI), patients with mild AD, and healthy controls using C-11-deuterium-L-deprenyl (C-11-DED) to measure monoamine oxidase B located in astrocytes. Along with C-11-DED PET, C-11-Pittsburgh compound B (C-11-PIB; fibrillar A beta deposition), F-18-FDG (glucose metabolism), T1 MRI, cerebrospinal fluid, and neuropsychologic data were acquired from the patients. Methods: C-11-DED PET was performed in MCI patients (n = 8; mean age 6 SD, 62.6 +/- 7.5 y; mean Mini Mental State Examination, 27.5 +/- 2.1), AD patients (n = 7; mean age, 65.1 +/- 6.3 y; mean Mini Mental State Examination, 24.4 +/- 5.7), and healthy age-matched controls (n = 14; mean age, 64.7 +/- 3.6 y). A modified reference Patlak model, with cerebellar gray matter as a reference, was chosen for kinetic analysis of the C-11-DED data. C-11-DED data from 20 to 60 min were analyzed using a digital brain atlas. Mean regional F-18-FDG uptake and C-11-PIB retention were calculated for each patient, with cerebellar gray matter as a reference. Results: ANOVA analysis of the regional C-11-DED binding data revealed a significant group effect in the bilateral frontal and bilateral parietal cortices related to increased binding in the MCI patients. All patients, except 3 with MCI, showed high C-11-PIB retention. Increased C-11-DED binding in most cortical and subcortical regions was observed in MCI C-11-PIB+ patients relative to controls, MCI C-11-PIB (negative) patients, and AD patients. No regional correlations were found between the 3 PET tracers. Conclusion: Increased C-11-DED binding throughout the brain of the MCI C-11-PIB+ patients potentially suggests that astrocytosis is an early phenomenon in AD development.
  •  
33.
  • Chiotis, Konstantinos, et al. (author)
  • Dual tracer tau PET imaging reveals different molecular targets for C-11-THK5351 and C-11-PBB3 in the Alzheimer brain
  • 2018
  • In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 45:9, s. 1605-1617
  • Journal article (peer-reviewed)abstract
    • Several tau PET tracers have been developed, but it remains unclear whether they bind to the same molecular target on the heterogeneous tau pathology. In this study we evaluated the binding of two chemically different tau-specific PET tracers (C-11-THK5351 and C-11-PBB3) in a head-to-head, in vivo, multimodal design. Nine patients with a diagnosis of mild cognitive impairment or probable Alzheimer's disease and cerebrospinal fluid biomarker evidence supportive of the presence of Alzheimer's disease brain pathology were recruited after thorough clinical assessment. All patients underwent imaging with the tau-specific PET tracers C-11-THK5351 and C-11-PBB3 on the same day, as well as imaging with the amyloid-beta-specific tracer C-11-AZD2184, a T1-MRI sequence, and neuropsychological assessment. The load and regional distribution of binding differed between C-11-THK5351 and C-11-PBB3 with no statistically significant regional correlations observed between the tracers. The binding pattern of C-11-PBB3, but not that of C-11-THK5351, in the temporal lobe resembled that of C-11-AZD2184, with strong correlations detected between C-11-PBB3 and C-11-AZD2184 in the temporal and occipital lobes. Global cognition correlated more closely with C-11-THK5351 than with C-11-PBB3 binding. Similarly, cerebrospinal fluid tau measures and entorhinal cortex thickness were more closely correlated with C-11-THK5351 than with C-11-PBB3 binding. This research suggests different molecular targets for these tracers; while C-11-PBB3 appeared to preferentially bind to tau deposits with a close spatial relationship to amyloid-beta, the binding pattern of C-11-THK5351 fitted the expected distribution of tau pathology in Alzheimer's disease better and was more closely related to downstream disease markers.
  •  
34.
  • Chiotis, Konstantinos, et al. (author)
  • Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm
  • 2016
  • In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:9, s. 1686-1699
  • Journal article (peer-reviewed)abstract
    • Purpose The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [F-18]THK5317 (also known as (S)-[F-18]THK5117) retention in different stages of Alzheimer's disease; and study any associations with markers of hypometabolism and amyloid-beta deposition. Methods Thirty-three individuals were enrolled, including nine patients with Alzheimer's disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer's disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [F-18]THK5317, [C-11] Pittsburgh compound B ([C-11]PIB), and [F-18]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [C-11]PIB-positive (n=11) and MCI [C-11]PIB-negative (n=2) groups. Results Test-retest variability for [F-18]THK5317-PET was very low (1.17-3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [C-11]PIB-positive) and dementia-stage Alzheimer's disease had significantly higher [F-18]THK5317 retention than healthy controls (p=0.002 and p=0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [F-18]THK5317 retention and [F-18]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [F-18]THK5317 and [C-11] PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [C-11]PIB but high [F-18]THK5317 retentions with a different regional distribution from that in Alzheimer's disease patients. Conclusions The tau-specific PET tracer [F-18]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.
  •  
35.
  • Chiotis, K., et al. (author)
  • Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer's disease dementia
  • 2018
  • In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:7, s. 1666-1673
  • Journal article (peer-reviewed)abstract
    • The development of tau-specific positron emission tomography (PET) tracers allows imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD) and other tauopathies. Eighteen patients with baseline investigations enroled in a 17-month follow-up study, including 16 with AD (10 had mild cognitive impairment and a positive amyloid PET scan, that is, prodromal AD, and six had AD dementia) and two with corticobasal syndrome. All patients underwent PET scans with [F-18]THK5317 (tau deposition) and [F-18]FDG (glucose metabolism) at baseline and follow-up, neuropsychological assessment at baseline and follow-up and a scan with [C-11]PIB (amyloid-beta deposition) at baseline only. At a group level, patients with AD (prodromal or dementia) showed unchanged [F-18]THK5317 retention over time, in contrast to significant decreases in [F-18]FDG uptake in temporoparietal areas. The pattern of changes in [F-18]THK5317 retention was heterogeneous across all patients, with qualitative differences both between the two AD groups (prodromal and dementia) and among individual patients. High [F-18]THK5317 retention was significantly associated over time with low episodic memory encoding scores, while low [F-18]FDG uptake was significantly associated over time with both low global cognition and episodic memory encoding scores. Both patients with corticobasal syndrome had a negative [C-11]PIB scan, high [F-18]THK5317 retention with a different regional distribution from that in AD, and a homogeneous pattern of increased [F-18]THK5317 retention in the basal ganglia over time. These findings highlight the heterogeneous propagation of tau pathology among patients with symptomatic AD, in contrast to the homogeneous changes seen in glucose metabolism, which better tracked clinical progression.
  •  
36.
  • Choo, Il Han, et al. (author)
  • Combination of f 18 fdg pet and cerebrospinal fluid biomarkers as a better predictor of the progression to alzheimer's disease in mild cognitive impairment patients
  • 2013
  • In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33:4, s. 929-939
  • Journal article (peer-reviewed)abstract
    • The biomarker-based new diagnostic criteria have been proposed for Alzheimer's disease (AD) spectrum. However, any biomarker alone has not been known to have satisfactory AD predictability. We explored the best combination model with baseline demography, neuropsychology, F-18-fluorodeoxyglucose positron emission tomography (FDG-PET), cerebrospinal fluid (CSF) biomarkers, and apolipoprotein E (APOE) genotype evaluation to predict progression to AD in mild cognitive impairment (MCI) patients. Alongitudinal clinical follow-up (mean, 44 months; range, 1.6-161.7 months) of MCI patients was done. Among 83 MCI patients, 26 progressed to AD (MCI-AD) and 51 did not deteriorate (MCI-Stable). We applied that univariate and multivariate logistic regression analyses, and multistep model selection for AD predictors including biomarkers. In univariate logistic analysis, we selected age, Rey Auditory Verbal Retention Test, parietal glucose metabolic rate, CSF total tau, and presence or not of at least one APOE epsilon 4 allele as predictors. Through multivariate stepwise logistic analysis and model selection, we found the combination of parietal glucose metabolic rate and total tau representing the best model for AD prediction. In conclusion, our findings highlight that the combination of regional glucose metabolic assessment by PET and CSF biomarkers evaluation can significantly improve AD predictive diagnostic accuracy of each respective method.
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37.
  • Damian, Marinella, et al. (author)
  • Single-Domain Amnestic Mild Cognitive Impairment Identified by Cluster Analysis Predicts Alzheimer's Disease in the European Prospective DESCRIPA Study
  • 2013
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 36:1-2, s. 1-19
  • Journal article (peer-reviewed)abstract
    • Background/Aims: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). Methods: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e. g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE >= 28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. Results: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (A beta(42), t-tau, APOE epsilon 4, and medial temporal atrophy), compared to SCI or naMCI. Conclusion: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings. Copyright (C) 2013 S. Karger AG, Basel
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38.
  • Darreh-Shori, T., et al. (author)
  • Differential CSF butyrylcholinesterase levels in Alzheimer's disease patients with the ApoE ε4 allele in relation to cognitive function and cerebral glucose metabolism.
  • 2006
  • In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 24:2, s. 326-333
  • Journal article (peer-reviewed)abstract
    • Butyrylcholinesterase (BuChE) is increased in the cerebral cortex of Alzheimer's disease (AD) patients, particularly those carrying ε4 allele of the apolipoprotein E gene (ApoE) and certain BuChE variants that predict increased AD risk and poor response to anticholinesterase therapy. We measured BuChE activity and protein level in CSF of eighty mild AD patients in relation to age, gender, ApoE ε4 genotype, cognition and cerebral glucose metabolism (CMRglc). BuChE activity was 23% higher in men than women ( p<0.03) and 40–60% higher in ApoE ε4 negative patients than in those carrying one or two ε4 alleles ( p<0.0004). CSF BuChE level correlated with cortical CMRglc. Patients with high to moderate CSF BuChE showed better cognitive function scores than others. We hypothesize that CSF BuChE varies inversely with BuChE in cortical amyloid plaques. Thus, low BuChE in a patient's CSF may predict extensive incorporation in neuritic plaques, increased neurotoxicity and greater central neurodegeneration.
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39.
  • Darreh-Shori, Taher, et al. (author)
  • Differential levels of apolipoprotein E and butyrylcholinesterase show strong association with pathological signs of Alzheimer's disease in the brain in vivo
  • 2011
  • In: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 32:12, s. 2320.e15-2320.e32
  • Journal article (peer-reviewed)abstract
    • Recently, we reported that 3 of the known risk factors of Alzheimer's disease (AD), i.e., advanced age, apolipoprotein E (ApoE) ε4, and female gender, are associated with differential levels of ApoE proteins and butyrylcholinesterase (BuChE) in the cerebrospinal fluid (CSF) of AD patients. The ApoE ε4 allele and certain BuChE polymorphisms synergistically affect the conversion rate of mild cognitive impairment (MCI) to AD. Here, we investigated interrelationships between ApoE and BuChE levels, and pathological markers of AD in vivo. CSF from patients with probable AD, assessed for cerebral glucose metabolism (CMRglc; n = 50) and Pittsburgh compound B (PIB) retention (β-amyloid [Aβ] load, n = 29) by positron emission tomography (PET), was used for measurement of BuChE, ApoE, Aβ, tau, phosphorylated tau (P-tau) and interleukin-1β (IL-1β) levels. Levels of ApoE and BuChE strongly correlated with CMRglc (fluorodeoxyglucose [FDG]-PET, r = 0.54, p < 0.0001, n = 50), cerebral Aβ load (PIB retention, r = 0.73, p < 0.0001, n = 29), and CSF P-tau (r = 0.73, p < 0.0001, n = 33). High ApoE protein was tied to low CMRglc and high PIB retention and P-tau. BuChE levels had opposite relationships. Other CSF covariates were levels of interleukin-1β and Aβ42peptide. The pattern of the patients' cognitive Z-scores strongly supported these observations. High ApoE protein was also linked to changes in 3 of the biodynamic properties of BuChE. In vitro analysis indicated that high ApoE protein levels were related to an increased pool of dormant BuChE molecules with an abnormally high intrinsic catalytic rate in CSF, which was “turned on” by excess Aβ peptides. The findings suggest that abnormally high levels of ApoE may play a causative role in the pathological events of AD, particularly those involving the early cholinergic deficit in the AD brain, through modulation of cholinesterases activities, hence disturbing the acetylcholine-dependent activity of neurons and nonexcitable cells such as glial cells.
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40.
  • Darreh-Shori, Taher, et al. (author)
  • Functional variability in butyrylcholinesterase activity regulates intrathecal cytokine and astroglial biomarker profiles in patients with Alzheimer's disease
  • 2013
  • In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:11, s. 2465-2481
  • Journal article (peer-reviewed)abstract
    • Butyrylcholinesterase (BuChE) activity is associated with activated astrocytes in Alzheimer's disease brain. The BuChE-K variant exhibits 30%-60% reduced acetylcholine (ACh) hydrolyzing capacity. Considering the increasing evidence of an immune-regulatory role of ACh, we investigated if genetic heterogeneity in BuChE affects cerebrospinal fluid (CSF) biomarkers of inflammation and cholinoceptive glial function. Alzheimer's disease patients (n = 179) were BCHE-K-genotyped. Proteomic and enzymatic analyses were performed on CSF and/or plasma. BuChE genotype was linked with differential CSF levels of glial fibrillary acidic protein, S100B, interleukin-1 beta, and tumor necrosis factor (TNF)-alpha. BCHE-K noncarriers displayed 100%-150% higher glial fibrillary acidic protein and 64%-110% higher S100B than BCHE-K carriers, who, in contrast, had 40%-80% higher interleukin-1b and 21%-27% higher TNF-alpha compared with noncarriers. A high level of CSF BuChE enzymatic phenotype also significantly correlated with higher CSF levels of astroglial markers and several factors of the innate complement system, but lower levels of proinflammatory cytokines. These individuals also displayed beneficial paraclinical and clinical findings, such as high cerebral glucose utilization, low beta-amyloid load, and less severe progression of clinical symptoms. In vitro analysis on human astrocytes confirmed the involvement of a regulated BuChE status in the astroglial responses to TNF-alpha and ACh. Histochemical analysis in a rat model of nerve injury-induced neuroinflammation, showed focal assembly of astroglial cells in proximity of BuChE-immunolabeled sites. In conclusion, these results suggest that BuChE enzymatic activity plays an important role in regulating intrinsic inflammation and activity of cholinoceptive glial cells and that this might be of clinical relevance. The dissociation between astroglial markers and inflammatory cytokines indicates that a proper activation and maintenance of astroglial function is a beneficial response, rather than a disease-driving mechanism. Further studies are needed to explore the therapeutic potential of manipulating BuChE activity or astroglial functional status. (C) 2013 Elsevier Inc. All rights reserved.
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41.
  • Ek, Lena, 1961-, et al. (author)
  • Analysis of Cognitive Dysfunction in Patients with Low-Grade Glioma
  • 2005
  • In: Journal of clinical psychology in medical settings. - : Springer. - 1068-9583 .- 1573-3572. ; 12:2, s. 165-173
  • Journal article (peer-reviewed)abstract
    • All living adults with histopatologically proven diagnosis of low-grade glioma in a Swedish county were identified with help of the Regional Cancer Register, half of them (n = 24) participated in a neuropsychological evaluation. A considerable variation was found in cognitive function within this group of patients, ranging from good ability to severe disturbance. Different patterns of cognitive dysfunction emerged resulting in three subgroups; patients with severe, mild, and minimal selective dysfunction. The patients with severe disturbance had a global dysfunction covering most assessed cognitive domains. Slow information-processing speed was obvious in the subgroups with both severe and mild dysfunction. Cognitive problems present in the best performing group seemed related to tumor localization. Cognitive function in the whole sample was related to histopathological diagnosis of the tumor, as well as to educational level of the patients. The nonworking patients had significantly poorer performance than the working patients.
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42.
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43.
  • Ek, Lena, 1961- (author)
  • Cognitive Deficits Reflecting Diffuse and Focal Brain Lesions Caused by Slow Growing Brain Tumors - Low-grade Gliomas
  • 2010
  • Doctoral thesis (other academic/artistic)abstract
    • The overall purpose was to characterize the impact that low-grade glioma (LGG) – a type of slowly growing brain tumor – has on cognitive functions. Paper I was an in-depth analysis of cognitive dysfunction of patients with histological proven LGG. The pattern varied among patients, revealing three subgroups: 1) patients with severe cognitive dysfunction; 2) patients with mild cognitive dysfunction; 3) patients with selective dysfunction due to tumor localization. In the first two subgroups the patients had slowed information-processing speed. Patients with a favorable prognosis performed better than those with unfavorable prognosis. Nonworking patients showed more pronounced dysfunction than working patients. Paper II studied cognitive functions of patients who were in the early stage of the disease and had not yet received any major medical treatments. Patients’ performances ranked at the lower end of normal limits, which contrasted with those of the individually matched controls, whose performances ranked at the upper end. Patients had slower information-processing-speed and less effective executive functions. Patients with frontal tumors had various executive problems due to tumor localization. Paper III investigated cognitive impairment at the individual level in relation to neurological symptoms, radiological characteristics of the tumor, depression, and fatigue.  Paper III included the same patients as Paper II. The results showed that the majority of the patients did not have more than selective impairment. One subgroup, consisting of younger patients with large left frontal tumors showed obvious cognitive impairment, including slowed information-processing speed. The thesis showed that diffuse brain injury was closely connected to LGG. A subgroup of patients in the early phase of the disease showed signs of mild diffuse brain injury. The majority of the patients who were in later stage of the disease displayed cognitive signs of diffuse brain injury.
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44.
  • Ek, Lena, 1961-, et al. (author)
  • Early cognitive impairment in a subset of patients with presumed low-grade glioma
  • 2010
  • In: Neurocase. - : Informa UK Limited. - 1355-4794 .- 1465-3656. ; 16:6, s. 503-511
  • Journal article (peer-reviewed)abstract
    • We investigated the presence of cognitive impairment, in adults with presumed low-grade glioma at early stage of disease prior to major treatments, in relation to neurological symptoms and radiological characteristics of the tumour. Sixteen patients were evaluated. A subset of patients was identified with clearly impaired cognition. Patients with cognitive impairment often had large tumours in the left frontal lobe, were relatively young, and most of them were males. We conclude that cognitive dysfunction may be present already at early stage of disease, and that early identification of patients at risk is warranted.
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45.
  • Engler, Henry, et al. (author)
  • Two-year follow-up of amyloid deposition in patients with Alzheimer's disease
  • 2006
  • In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 129:Pt 11, s. 2856-2866
  • Journal article (peer-reviewed)abstract
    • Beta amyloid is one of the major histopathological hallmarks of Alzheimer's disease. We recently reported in vivo imaging of amyloid in 16 Alzheimer patients, using the PET ligand N-methyl[11C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole (PIB). In the present study we rescanned these 16 Alzheimer patients after 2.0 +/- 0.5 years and have described the interval change in amyloid deposition and regional cerebral metabolic rate for glucose (rCMRGlc) at follow-up. Sixteen patients with Alzheimer's disease were re-examined by means of PET, using PIB and 2-[18F]fluoro-2-deoxy-d-glucose (FDG) after 2.0 +/- 0.5 years. The patients were all on cholinesterase inhibitor treatment and five also on treatment with the N-methyl-d-aspartate (NMDA) antagonist memantine. In order to estimate the accuracy of the PET PIB measurements, four additional Alzheimer patients underwent repeated examinations with PIB within 20 days (test-retest). Relative PIB retention in cortical regions differed by 3-7% in the test-retest study. No significant difference in PIB retention was observed between baseline and follow-up while a significant (P < 0.01) 20% decrease in rCMRGlc was observed in cortical brain regions. A significant negative correlation between rCMRGlc and PIB retention was observed in the parietal cortex in the Alzheimer patients at follow-up (r = 0.67, P = 0.009). A non-significant decline in Mini-Mental State Examination (MMSE) score from 24.3 +/- 3.7 (mean +/- standard deviation) to 22.7 +/- 6.1 was measured at follow-up. Five of the Alzheimer patients showed a significant decline in MMSE score of >3 (21.4 +/- 3.5 to 15.6 +/- 3.9, P < 0.01) (AD-progressive) while the rest of the patients were cognitively more stable (MMSE score = 25.6 +/- 3.1 to 25.9 +/- 3.7) (AD-stable) compared with baseline. A positive correlation (P = 0.001) was observed in the parietal cortex between Rey Auditory Verbal Learning (RAVL) test score and rCMRGlc at follow-up while a negative correlation (P = 0.018) was observed between RAVL test and PIB retention in the parietal at follow-up. Relatively stable PIB retention after 2 years of follow-up in patients with mild Alzheimer's disease suggests that amyloid deposition in the brain reaches a plateau by the early clinical stages of Alzheimer's disease and therefore may precede a decline in rCMRGlc and cognition. It appears that anti-amyloid therapies will need to induce a significant decrease in amyloid load in order for PIB PET images to detect a drug effect in Alzheimer patients. FDG imaging may be able to detect a stabilization of cerebral metabolism caused by therapy administered to patients with a clinical diagnosis of Alzheimer's disease.
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46.
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47.
  • Ericsson, Kjerstin, et al. (author)
  • The short human figure drawing scale for evaluation of suspect cognitive dysfunction in old age
  • 1994
  • In: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 19:3, s. 243-51
  • Journal article (peer-reviewed)abstract
    • Human figure drawings have been widely used to assess cognitive development in children. In the present study, free-hand human figure drawings were examined for 62 demented patients, and 60 normal elderly subjects. The drawings were scored for 53 body details using a method derived from work with children. A short scale of 15 details was developed by selecting body details with high item-total correlations which are simple to score even for untrained staff. This short scale had excellent interscorer and test-retest reliability and excellent concurrent validity as well. It correlated highly with the Mini-Mental State Examination, a commonly used screening test for dementia. The short scale discriminated demented and non-demented subjects and different levels of dementia severity as graded by the Clinical Dementia Rating Scale. However, no differences were observed between Alzheimer patients and patients with vascular dementia concerning presence of details in human figure drawings.
  •  
48.
  • Eriksdotter-Jönhagen, Maria, et al. (author)
  • Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease.
  • 2012
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 33:1, s. 18-28
  • Journal article (peer-reviewed)abstract
    • Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer's disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability.
  •  
49.
  • Farid, Karim, et al. (author)
  • Case Report of Complex Amyotrophic Lateral Sclerosis with Cognitive Impairment and Cortical Amyloid Deposition.
  • 2015
  • In: Journal of Alzheimer's disease : JAD. - 1875-8908 .- 1387-2877. ; 47:3, s. 661-7
  • Journal article (peer-reviewed)abstract
    • Amyotrophic lateral sclerosis (ALS), a fatal disease of unknown origin, affects motor neurons in the primary motor cortex, brainstem, and spinal cord. Cognitive impairment may occur before the motor symptoms. We present a patient who was initially diagnosed with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) but who developed ALS-like symptoms during follow-up and died shortly thereafter. A 60-year-old subject with cognitive impairment underwent neuropsychological testing, cerebrospinal fluid (CSF) analysis, structural imaging (computed tomography and magnetic resonance imaging) and functional imaging [11C]-Pittsburgh compound B (PIB) positron emission tomography (PET), [18F]-fluorodeoxyglucose (FDG) PET, and [11C]-deuterium-L-deprenyl (DED) PET. Neuropsychological testing showed episodic memory impairment. CSF P-tau and T-tau levels were elevated. CSF amyloid-β (Aβ)42 levels were initially normal but became pathological during follow-up. MCI was diagnosed. [18F]-FDG PET showed hypometabolism in the left temporal and prefrontal cortices and [11C]-PIB PET demonstrated amyloid plaque deposition in the prefrontal, posterior cingulate, and parietal cortices. [11C]-DED PET showed high brain accumulation consistent with astrocytosis. The memory impairment progressed and AD was diagnosed. Motor impairments developed subsequently and, following additional neurological evaluation, ALS was diagnosed. The disease progressed rapidly and the patient died with pronounced motor symptoms three years after the initial cognitive assessment. Since relatives refused autopsy, postmortem analysis was not possible.
  •  
50.
  • Forsberg, A, et al. (author)
  • High PIB Retention in Alzheimer's Disease is an Early Event with Complex Relationship with CSF Biomarkers and Functional Parameters
  • 2010
  • In: Current Alzheimer Research. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 7:1, s. 56-66
  • Journal article (peer-reviewed)abstract
    • Background:New in vivo amyloid PET imaging tracers, such as 11C-PIB, provide possibilities to deeper understand the underlying pathological processes in Alzheimers disease (AD). In this study we investigated how 11C-PIB retention is related to cerebral glucose metabolism, episodic memory and CSF biomarkers.Method:Thirty-seven patients with mild AD and 21 patients with mild cognitive impairment (MCI) underwent PET examinations with the amyloid tracer 11C-PIB, 18F-FDG for measurement of regional cerebral metabolic rate of glucose (rCMRglc), assessment of episodic memory and assay of cerebral spinal fluid (CSF) levels of amyloid-ß (Aβ1-42), total tau and phosphorylated tau respectively. Analyses were performed using Statistical Parametric Mapping (SPM) and regions of interest (ROIs).Results:Pooled data from AD and MCI patients showed strong correlations between 11C-PIB retention, levels of CSF biomarkers (especially Aß1-42), rCMRglc and episodic memory. Analysis of the MCI group alone revealed significant correlations between 11C-PIB retention and CSF biomarkers and between CSF biomarkers and episodic memory respectively. A strong correlation was observed in the AD group between rCMRglc and episodic memory as well as a significant correlation between 11C-PIB retention and rCMRglc in some cortical regions. Regional differences were observed as sign for changes in temporal patterns across brain regions.Conclusions:A complex pattern was observed between pathological and functional markers with respect to disease stage (MCI versus AD) and brain regions. Regional differences over time were evident during disease progression. 11C-PIB PET and CSF Aß1-42 allowed detection of prodromal stages of AD. Amyloid imaging is useful for early diagnosis and evaluation of new therapeutic interventions in AD.
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