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1.
  • Aarsland, D, et al. (author)
  • Early discriminatory diagnosis of dementia with Lewy bodies. The emerging role of CSF and imaging biomarkers
  • 2008
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 25:3, s. 195-205
  • Journal article (peer-reviewed)abstract
    • <i>Background:</i> The clinical diagnostic criteria for dementia with Lewy bodies (DLB) have a low sensitivity, and there are no generally accepted biomarkers to distinguish DLB from other dementias. Our aim was to identify biomarkers that may differentiate DLB from Alzheimer’s disease (AD). <i>Method:</i> We performed a systematic literature search for studies of EEG, imaging techniques and genetic and CSF markers that provide sensitivity and specificity in the identification of DLB. <i>Results:</i> The best evidence was for scintigraphy of the striatal dopamine transporter system using FP-CIT SPECT. Several small scintigraphy studies of cardiovascular autonomic function using metaiodobenzylguanidine SPECT have reported promising results. Studies exploring innovative techniques based on CSF have reported interesting findings for the combination of amyloid β (aβ) isoforms as well as α-synuclein, and there are interesting results emerging from preliminary studies applying proteomic techniques. Data from studies using structural MRI, perfusion SPECT, genetics and EEG studies show differences between DLB and AD but only at a group level. <i>Conclusion:</i> Several potential biomarkers for the differential diagnosis of probable DLB and AD have shown good diagnostic accuracy in the research setting. Data from large multicentre studies and from studies with autopsy confirmation exist for scintigraphy of the dopamine transporter system. Future studies should explore its value in possible DLB and for clinical management and health economics.
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2.
  • Aarsland, D, et al. (author)
  • Frequency and case identification of dementia with Lewy bodies using the revised consensus criteria
  • 2008
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 26:5, s. 445-452
  • Journal article (peer-reviewed)abstract
    • <i>Objective:</i> To find the proportion of dementia with Lewy bodies (DLB) in a referral cohort of patients with a first-time diagnosis of mild dementia. <i>Background:</i> The proportion of DLB among the dementia sufferers is not known and the clinical consensus criteria have low sensitivity. We employed the revised DLB criteria to study the proportion with DLB in a community sample of patients with mild dementia. <i>Methods:</i> From March 2005 to March 2007, we included 196 patients from referrals to all geriatric medicine, old age psychiatry and neurology outpatient clinics in Rogaland and Hordaland counties in Western Norway. Standardized clinical instruments and diagnostic criteria were employed. <i>Results:</i> 65% had Alzheimer dementia, 20% DLB (16% probable DLB), 5.6% vascular dementia, 5.6% Parkinson disease with dementia, 2.0% frontotemporal dementia and 1.5% alcoholic dementia. There were no significant differences in the proportion with DLB according to age bands and dementia severity groups. The revised criteria for a clinical diagnosis of DLB increased the proportion of probable DLB by 25% compared to the previous criteria. <i>Conclusion:</i> DLB is common in patients with mild dementia, and is the second most common type of dementia. The introduction of new clinical criteria for DLB leads to an increase in the proportion diagnosed with probable DLB.
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3.
  • Aguero-Torres, H, et al. (author)
  • Rethinking the dementia diagnoses in a population-based study : What is Alzheimer's disease and what is vascular dementia? A study from the Kungsholmen Project
  • 2006
  • In: Dementia and Geriatric Cognitive Disorders. - Basel : Karger. - 1420-8008 .- 1421-9824. ; 22:3, s. 244-249
  • Journal article (peer-reviewed)abstract
    • Objective: To explore the hypothesis that older adults often are affected by more than one disease, making the differential diagnosis between Alzheimer’s disease (AD) and vascular dementia (VaD) difficult. Methods: Incident dementia cases (n = 308) from a population-based longitudinal study of people 75+ years were investigated. The DSM-III-R criteria were used for the clinical diagnosis of dementia. Data on vascular disorders (hypertension, cerebrovascular and ischemic heart diseases, heart failure, atrial fibrillation, diabetes) as well as type of onset/course of dementia were used retrospectively to reclassify dementias. Results: Only 47% of the AD cases were reclassified as pure AD without any vascular disorder. Among subjects with AD and with a vascular component, cerebrovascular disease was the most common (41%). Only 25% of VaD were reclassified as pure VaD. Further, 26% of the pure AD subjects developed a vascular disorder in the following 3 years. Conclusions: Both vascular and degenerative mechanisms may often contribute to the expression of dementia among the elderly. Most of the AD cases have vascular involvements, and pure dementia types in very old subjects constitute only a minority of dementia cases.
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4.
  • Aho, Leena, et al. (author)
  • Systematic appraisal using immunohistochemistry of brain pathology in aged and demented subjects.
  • 2008
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 25:5, s. 423-32
  • Journal article (peer-reviewed)abstract
    • BACKGROUND/AIMS: Abnormal processing of hyperphosphorylated tau (HPtau), amyloid-beta (Abeta) and alpha-synuclein (alphaS) proteins is considered as causative with regard to the clinical symptoms in age-related neurodegenerative diseases.METHODS: In this retrospective, postmortem study applying immunohistochemical methodology, we assessed Alzheimer's-disease (AD)-related HPtau and Abeta pathology in 178 subjects with alphaS pathology.RESULTS: These pathologies were frequently seen concomitantly, i.e. HPtau in 83% and Abeta in 62% of the alphaS-positive cases. Furthermore, the striatum was frequently involved, particularly in subjects with cognitive impairment (65%). The predictive value of widespread HPtau pathology, i.e. stages V-VI, with respect to cognitive impairment was high, since all 18 subjects presenting with this stage were demented. In contrast, the predictive value of widespread alphaS pathology, i.e. stages 5-6 according to Braak's Parkinson disease staging, was debatable. Fifty-three percent of the subjects with widespread alphaS pathology and no or mild AD-related HPtau pathology were cognitively unimpaired. It is noteworthy that striatal Abeta pathology was more often seen in demented subjects independently of HPtau and/or alphaS status.CONCLUSION: The causative pathology in subjects with clinically diagnosed dementia with Lewy bodies needs to be clarified in future studies.
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5.
  • Alenius, M, et al. (author)
  • Education-Based Cutoffs for Cognitive Screening of Alzheimer's Disease
  • 2022
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 51:1, s. 42-55
  • Journal article (peer-reviewed)abstract
    • <b><i>Introduction:</i></b> The educational background and size of the elderly population are undergoing significant changes in Finland during the 2020s. A similar process is likely to occur also in several European countries. For cognitive screening of early Alzheimer’s disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy. The aim of the present study was to examine the effects of education, age, and gender on the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery (CERAD-nb) in a large register-based, clinical sample of patients with mild AD and nondemented at-risk persons from the general population (controls) and to examine whether corrected cutoff scores would increase the accuracy of differentiation between the 2 groups. <b><i>Methods:</i></b> CERAD-nb scores were obtained from AD patients (<i>n</i> = 389, 58% women, mean age 74.0 years) and from controls (<i>n</i> = 1,980, 52% women, mean age 68.5 years). The differences in CERAD-nb performance were evaluated by univariate GLM. Differentiation between the 2 groups was evaluated using a receiver operating characteristic (ROC) curve, where a larger area under the ROC curve represents better discrimination. Youden’s J was calculated for the overall performance and accuracy of each of the measures. <b><i>Results:</i></b> Of the demographic factors, education was the strongest predictor of CERAD-nb performance, explaining more variation than age or gender in both the AD patients and the controls. Education corrected cutoff scores had better diagnostic accuracy in discriminating between the AD patients and controls than existing uncorrected scores. The highest level of discrimination between the 2 groups overall was found for two CERAD-nb total scores. <b><i>Conclusions:</i></b> Education-corrected cutoff scores were superior to uncorrected scores in differentiating between controls and AD patients especially for the highest level of education and should therefore be used in clinical cognitive screening, also as the proportion of the educated elderly is increasing substantially during the 2020s. Our results also indicate that total scores of the CERAD-nb are better at discriminating AD patients from controls than any single subtest score. A digital tool for calculating the total scores and comparing education-based cutoffs would increase the efficiency and usability of the test.
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6.
  • Algotsson, A, et al. (author)
  • Patients with Alzheimer's disease may be particularly susceptible to adverse effects of statins
  • 2004
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 17:3, s. 109-116
  • Journal article (peer-reviewed)abstract
    • In epidemiological, cross-sectional studies, treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) prevented to a large extent the development of Alzheimer’s disease (AD), but the results of randomized, placebo-controlled studies, focused on statin therapy in patients with ischemic heart disease (IHD), are at variance. Nonetheless, data from epidemiological, longitudinal studies in humans as well as studies on transgenic mouse models and cultured neuronal cell lines indicate that cholesterol may contribute to the pathogenesis of AD. Statins have proven therapeutic and preventive effects in IHD and other vascular diseases in man. They generally are well tolerated, but some adverse effects, probably due to antiproliferative and proapoptotic properties of the statins, are matters of concern. AD patients may be extrasusceptible to adverse effects of statins due to preexisting aberrations in signal transduction and energy metabolism in the neurons and a perturbed cholesterol metabolism in the brain. This problem might be addressed in randomized, double-blind studies with statins in AD. The statins differ from each other in several aspects, and they are not considered to be therapeutically interchangeable. It could be fruitful to use both a placebo and two different types of statins, i.e. an essentially hydrophilic statin and a lipophilic statin, in a double-blinded fashion, and to compare the effects on the cognitive decline in AD.
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7.
  • Allard, Per, et al. (author)
  • Caudate nucleus dopamine D-2 receptors in vascular dementia
  • 2002
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 14:1, s. 22-25
  • Journal article (peer-reviewed)abstract
    • Caudate nucleus dopamine (DA) D-2 receptors were studied in patients with vascular dementia (VaD) and in a control group using [H-3]raclopride as a radioligand. There was no significant difference in the number of DA D-2 receptors in the VaD group as compared with controls. The binding affinity was significantly lower in the VaD group. When the VaD group was subdivided into subjects with or without neuroleptic treatment, there were no differences in the numbers of receptors as compared with controls, and the significant differences in binding affinity remained for both VaD subgroups. The present results are. discussed with reference to the previous finding of a reduced density of caudate nucleus DA uptake sites in the same VaD group and to results from studies on DA D-2 receptors in Alzheimer's disease and Parkinson's disease. Copyright (C) 2002 S. Karger AG, Basel.
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8.
  • Allard, Per, et al. (author)
  • Reduced number of caudate nucleus dopamine uptake sites in vascular dementia.
  • 1999
  • In: Dementia and Geriatric Cognitive Disorders. - 1420-8008 .- 1421-9824. ; 10:2, s. 77-80
  • Journal article (peer-reviewed)abstract
    • The dopamine (DA) uptake sites in the caudate nucleus were studied in patients with vascular dementia (VAD) and in a control group using the presynaptic DA uptake site marker [3H][2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane] as radioligand. There was a significant decrease in the number of DA uptake sites in the VAD group, while the binding affinity was unchanged. The present results indicate that in the patients investigated, the cerebrovascular disease process involves dopaminergic neuron terminals in the caudate nucleus. Our findings are discussed in relation to the reductions in number of DA uptake sites that have previously been revealed in Alzheimer's and Parkinson's diseases.
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9.
  • Almkvist, O, et al. (author)
  • Responder characteristics to a single oral dose of cholinesterase inhibitor: a double-blind placebo-controlled study with tacrine in Alzheimer patients
  • 2001
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:1, s. 22-32
  • Journal article (peer-reviewed)abstract
    • A proportion of Alzheimer’s disease (AD) patients treated for several months with cholinesterase (ChE) inhibitors have shown some favorable response on cognition, but the characteristics of the responders are still unclear. This study attempts to identify the characteristics of individuals with a positive behavioral response after a double-blind randomized administration of a single oral dose of tacrine (40 mg) and placebo to AD patients. Furthermore, the relationship between single-dose and long-term responders are examined. Twenty-four mildly to very mildly demented AD patients participated in the study. They all fulfilled the diagnosis of probable AD according to NINCDS-ADRDA criteria. Active treatment (tacrine 40 mg) and placebo was administered in random order on 2 consecutive days, and the effects were evaluated within 2 h using neuropsychological tests (assessing visuospatial ability, episodic memory and attention), registration of EEG activity and measurement of red blood cells (RBC) acetylcholinesterase (AChE), ChE activity and concentrations of tacrine and its metabolites in plasma. Results demonstrated significant improvement, tacrine compared to placebo, in measures of attention, but not in episodic memory or visuospatial ability. A single-dose response was therefore defined in terms of improvement in attention. The tacrine plasma concentration (pcTHA) showed a positively skewed distribution (mean ± SD: 10.5 ± 11.8, range: 1.0–51.8 ng/ml). There were no significant differences between single-dose responders compared to nonresponders in pcTHA, metabolites of tacrine, inhibition of AChE in RBC, tau levels in CSF, AChE activity in CSF or plasma and demographic variables. However, single-dose responders showed a higher right frontal alpha/theta ratio on EEG and had lower glucose metabolism in the parietal-temporal association cortex at baseline. In addition, the frequency of apolipoprotein E (APOE) &#917;4 alleles was higher in responders. Interestingly, the single-dose response was related to the long-term response, although not significantly, which probably was due to lack of power. To conclude, the present study identified single-dose responders in terms of improved attentional performance associated with a relatively higher alpha/theta activity in the right frontal regions of the brain measured on EEG and predominance of APOE &#917;4 allele.
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10.
  • 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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11.
  • 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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12.
  • Andersson, Christin, et al. (author)
  • Lifestyle Factors and Subjective Cognitive Impairment in Patients Seeking Help at a Memory Disorder Clinic : The Role of Negative Life Events
  • 2019
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger. - 1420-8008 .- 1421-9824. ; 48:3-4, s. 196-206
  • Journal article (peer-reviewed)abstract
    • Background/Aims: A large proportion of patients at memory disorders clinics are classified as having subjective cognitive impairment (SCI). Previous research has investigated whether particular lifestyle factors known to affect cognition can be useful in differentiating patients who do not show objective evidence of memory decline. There may also exist subgroups of patients with respect to lifestyle factors that could help clinicians to understand the patient group that presents to memory clinics. These may differ in diagnostic outcome. Very little is known about potential subgroups; however, but such information may help guide interventions and potentially eliminate unnecessary diagnostic procedures. The current study investigated patterns of lifestyle-related variables, including stress, sleep, sensory sensitivity, depression, and negative life events in patients presenting to a memory disorders clinic. The aim was to determine whether subgroups existed and whether it was possible to distinguish those with objectively impaired cognition. Methods: One hundred and seventy-eight patients (mean age 58 years) from a University Hospital Memory Disorders Clinic. Results: Cluster analysis identified three groups of lifestyle-related variables. Strong determinants of clusters were negative life events and age. Patients with a high number of negative life events also tended to have highest self-reported memory complaint, higher levels of stress, depression, and sensory sensitivity. However, they did not perform the worst on memory testing. In contrast, individuals who performed the worst on memory tests were older, tended to have the least memory complaints, and less negative lifestyle factors; this group also included the highest proportion of patients with mild cognitive impairment and had the lowest median amyloid A-beta 42 (A beta 42). The group with the best cognitive performance were younger, included the highest proportion of patients with SCI and the highest median A beta 42. On lifestyle variables, their ratings fell in between the other groups. Conclusions: Lifestyle subgroups of patients were determined by stress, emotional problems, and age. The groups were significantly associated with A beta 42 and diagnostic outcome. This pattern may confound the differentiation between objective and subjective memory problems. Asking about lifestyle variables, in conjunction with neuropsychological testing, could potentially identify individuals who are not likely to have objective memory impairment and guide interventions.
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13.
  • Andersson, Maria A, et al. (author)
  • Electroencephalogram variability in dementia with lewy bodies, Alzheimer's disease and controls.
  • 2008
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 26:3, s. 284-290
  • Journal article (peer-reviewed)abstract
    • BACKGROUND/AIM: Dementia with Lewy bodies (DLB) is probably still underdiagnosed in the clinical setting. Previous studies have suggested a relationship between fluctuations in attention and electroencephalogram (EEG) measures. Since fluctuation in attention is a core symptom of DLB, we sought to further explore whether EEG measures could help differentiate DLB from Alzheimer's disease (AD) and healthy controls. METHODS: The EEGs of 20 patients with DLB, 64 patients with AD and 54 elderly controls were assessed in regard to frequencies, coherence, and variability. RESULTS: Greater variability was seen in delta-band power over 2-second intervals in parietal electrodes of DLB patients. The DLB group had a higher degree of overall coherence in the delta band and a lower degree of overall coherence in the alpha band than the other groups. Finally, EEG measures could distinguish DLB patients from AD patients and controls with areas under the receiver operating characteristic curves ranging between 0.75 and 0.80 and between 0.91 and 0.97, respectively. CONCLUSIONS: We suggest that the difference in variability may be associated with the fluctuating cognition seen in DLB. This might have clinical implications as guidance in the diagnosis of DLB. The EEG analysis is simple enough to be possible to apply in clinical practice.
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14.
  • Andin, Josefine, 1979-, et al. (author)
  • Rivastigmine as a Modulator of the Neuronal Glutamate Transporter rEAAC1 mRNA Expression
  • 2005
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 19:1, s. 18-23
  • Journal article (peer-reviewed)abstract
    • Alzheimer’s disease is a neurodegenerative disorder that affects the cholinergic, glutamatergic and monoaminergic systems in the neocortex and hippocampus. Today, the major pharmacological treatment involves the use of acetylcholinesterase inhibitors (AChEIs). In this study, an in situ hybridisation technique (using digoxigenin-labelled cRNA probes) was used to elucidate changes in mRNA expression of the neuronal glutamate transporter, rat excitatory amino carrier 1 (rEAAC1), after treatment with the AChEI rivastigmine. Compared with saline-treated rats, the rats subchronically (3 days) and chronically (21 days), but not acutely, treated with rivastigmine showed a significant increase in rEAAC1 mRNA expression in the hippocampal areas cornu anterior 1 (CA1), CA2, CA3 and dentate gyrus (p < 0.01), but not in the cortical areas. These results provide the first evidence that the glutamatergic system is modulated following acetylcholinesterase inhibition by rivastigmine, a finding, which is likely to be of importance for the clinical effects.
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15.
  • Andin, Ulla, et al. (author)
  • A Clinico-Pathological Study of Heart and Brain Lesions in Vascular Dementia.
  • 2005
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 19:4, s. 222-228
  • Journal article (peer-reviewed)abstract
    • All vascular dementia (VaD) cases, neuropathologically verified in a longitudinal prospective dementia project, were classified according to the vascular brain lesion type and related to the dementia type and cardiovascular pathology. From 1976 to 1995, there were 175 VaD cases, 49 of which were pure, without Alzheimer pathology and only one type of cerebrovascular lesion. Furthermore, it was found that 6 cases suffered hypoxic hypoperfusive disease, while 7 were found to have large vessel disease and 36 small vessel disease. In addition to Alzheimer pathology, more than one type of vascular brain pathology was found in the remaining 126 cases. In these cases, diagnosed in accordance with the predominant type of VaD, hypoxic-hypoperfusive lesions were found in 55, large vessel lesions in 50 and small vessel lesions in 110 cases. It should be stressed that 87% of all cases with hypoxic hypoperfusive lesions also had Alzheimer pathology. Cardiovascular and aortic pathologies were more prevalent in small vessel dementia than in the other VaD groups. Clinically diagnosed arterial hypertension was significantly associated with small vessel dementia, but not with hypoxic-hypoperfusive dementia. Cardiovascular symptoms varied considerably in frequency between different dementia groups. VaD is a heterogeneous group regarding lesions caused by different pathophysiological mechanisms and with different combinations of brain pathologies. It is therefore necessary to identify the various types of vascular brain lesions for a correlation with clinical symptoms and for diagnostic purposes in the search for risk factors and therapeutic strategies.
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16.
  • Annerbo, S, et al. (author)
  • A prospective study on the development of Alzheimer's disease with regard to thyroid-stimulating hormone and homocysteine
  • 2009
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:3, s. 275-280
  • Journal article (peer-reviewed)abstract
    • <i>Background/Aim: </i>The combination of elevated total homocysteine (tHcy) levels and low levels of thyroid-stimulating hormone (TSH) are linked to Alzheimer’s disease (AD) in some studies, although the evidence is mixed. Our objective was to prospectively investigate the association between tHcy and TSH and the subsequent development of AD. <i>Methods:</i> A subsample of 200 nondemented subjects was taken from the Kungsholmen Project, a population-based study among people ≥75 years. Information about tHcy and TSH levels were taken from the baseline investigation of the Kungsholmen Project study. <i>Results: </i>Increased tHcy levels were related to an elevated risk of AD (n = 61) after a mean follow-up time of 6.7 years. People with high tHcy (the 3rd tertile) had more than twice as high a risk of developing AD than those with low tHcy, even after adjusting for age, sex, education, ApoE status, MMSE score and laboratory parameters. tHcy was negatively correlated with TSH (p = 0.02). There was neither an influence of TSH nor an interaction between tHcy and TSH in the development of AD. <i>Conclusions: </i>These results suggest that homocysteine, but not TSH, is involved in the development of AD. The connection between elevated tHcy and low TSH levels needs to be studied further.
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17.
  • Annerbo, S, et al. (author)
  • The relation between homocysteine levels and development of Alzheimer's disease in mild cognitive impairment patients
  • 2005
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 20:4, s. 209-214
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to investigate over a 3-year period the connection between homocysteine (Hcy) levels and development of Alzheimer’s disease (AD) in patients with mild cognitive impairment (MCI). Hcy was analyzed in 68 men, mean age 65 years, and 68 women, mean age 64 years. Age, sex, cobalamin, folate, creatinine, and thyroid profiles as well as results of Mini-Mental State Examination at the first visit to the memory investigation unit of a geriatric department were recorded from patient journals collected between 1992 and 1999. The total numbers of persons who converted to AD within a period of 3 years from initial investigation with baseline Hcy sampling was 12 of 46 (26%) males, and 18 of 50 women (36%). The total percentage of men and women converting to AD was 31%. Thirty-three percent of men with Hcy levels >20 µmol/l converted to AD. The corresponding figure for men with Hcy levels 20–17 µmol/l was 50%, whereas none of the 18 men with Hcy levels <17 µmol/l converted to AD. These differences were statistically significant. There was also a statistically significant difference between the percentage of women with Hcy levels >16 µmol/l who converted to AD (45%) as compared to those with Hcy levels <16 µmol/l who converted (21%). These findings are inconsistent with the results of other studies showing a positive correlation with hyperhomocysteinemia and occurrence of AD. However, our findings tentatively suggest a possible protective effect of low/normal Hcy levels on dementia conversion in MCI patients.
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18.
  • Attner, Bo, et al. (author)
  • Low Cancer Rates among Patients with Dementia in a Population-Based Register Study in Sweden.
  • 2010
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 30:1, s. 39-42
  • Journal article (peer-reviewed)abstract
    • Background: Some studies have suggested a lower incidence of cancer in patients with dementia. We studied this further for 18 cancer types in population-based registers. Methods: In 19,756 cases and in 147,324 age- and sex-matched controls a diagnosis of dementia was studied 9-45 months prior to the diagnosis of cancer. Results: Overall a diagnosis of dementia was significantly less common among the cancer cases (risk ratio, RR = 0.60; 95% CI = 0.52-0.69). Conclusion: The study confirms previous findings that patients with dementia have a lower risk of cancer. Because the effect was seen for all tumour types and especially for patients older than 70 years and since the deficit was more pronounced for patients with tumours situated within the body, the data suggest that malignancies are underdiagnosed for persons with dementia.
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19.
  • Auning, E, et al. (author)
  • Early and presenting symptoms of dementia with lewy bodies
  • 2011
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 32:3, s. 202-208
  • Journal article (peer-reviewed)abstract
    • <i>Background/Aims:</i> To explore the presenting and early symptoms of dementia with Lewy bodies (DLB). <i>Method:</i> Patients with mild dementia fulfilling diagnostic criteria for DLB (n = 61) and Alzheimer’s disease (AD) (n = 109) were recruited from outpatient dementia clinics in western Norway. At diagnosis, caregivers were asked which symptom had been the presenting symptom of dementia. <i>Results:</i> Caregivers reported that memory impairment was the most common presenting symptom in DLB (57%), followed by visual hallucinations (44%), depression (34%), problem solving difficulties (33%), gait problems (28%), and tremor/stiffness (25%). In contrast, 99% of AD carers reported impaired memory as a presenting symptom, whereas visual hallucinations were a presenting symptom in 3% of the AD cases. <i>Conclusion:</i> DLB should be suspected in predementia cases with visual hallucinations.
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20.
  • 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.
  •  
21.
  • 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
  •  
22.
  • Axelman, K, et al. (author)
  • Apolipoprotein E and alpha1-antichymotrypsin genotypes and age of onset of familial Alzheimer's disease
  • 1999
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 10:1, s. 1-5
  • Journal article (peer-reviewed)abstract
    • Apolipoprotein E (APOE) and α<sub>1</sub>-antichymotrypsin (ACT) genotype and allele frequency distribution were investigated in 113 familial Alzheimer’s disease (AD) cases. A significantly higher σ4 frequency was observed in patients with an age of onset between 55–64 and 65–74 years compared to individuals with later or earlier onset. No difference in ACT <i>A</i> allele frequency was seen in any onset group, nor was any influence of ACT genotypes on the age of onset observed. However, the mean age of onset was lowered by the presence of the ACT/AA and ACT/TT genotypes among APOE σ3/3 bearers. Possible APOE effects on age of onset were evaluated in 78 affected sib pairs. An earlier age of onset was observed in siblings with an σ4 allele compared to siblings without an σ4 allele. This supports the notion that the σ4 allele promotes an earlier age of onset. However, in siblings with the same APOE genotype, a wide range of onset was seen, indicating that unknown genetic or environmental factors affect the expression of AD.
  •  
23.
  • Axelman, K, et al. (author)
  • Life situation, coping and quality of life in people with high and low risk of developing Alzheimer's disease
  • 2003
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 16:4, s. 220-228
  • Journal article (peer-reviewed)abstract
    • The psychosocial consequences of being at different risk for inheriting Alzheimer’s disease (AD) were investigated in a high-risk group (n = 106) and a low-risk group (n = 37). Non-affected individuals from families with AD in two or more generations answered questions about their life situation, quality of life and coping. Their answers were compared with a population sample (n = 408). The high-risk group assessed the quality of their personal relationships and everyday life higher than did the population sample. They also used less emotive and supportive coping strategies compared with the population sample. Nearly 90% in the high-risk group felt anxiety concerning their own risk or the risk of their children and grandchildren of developing AD. About 50% of the respondents complained about a lack of information. The pieces of information they asked for were early signs of the disease, treatment, and practical information on how to handle everyday life with an affected relative.
  •  
24.
  • Basun, H, et al. (author)
  • Plasma levels of Abeta42 and Abeta40 in Alzheimer patients during treatment with the acetylcholinesterase inhibitor tacrine
  • 2002
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 14:3, s. 156-160
  • Journal article (peer-reviewed)abstract
    • Deregulation of amyloid precursor protein (APP) processing with increased production of amyloid β-peptide (Aβ) is considered to be a key pathogenic event in Alzheimer’s disease (AD). It has been suggested that stimulation of the muscarinic M<sub>1</sub> receptor subtype affects APP processing and leads to a change in Aβ concentration. To test the hypothesis that treatment with a cholinesterase inhibitor could change the levels of Aβ in plasma, we measured Aβ42 and Aβ40 plasma levels in AD subjects before tacrine treatment and at weeks 2 and 6 of treatment. Treatment with tacrine had no statistically significant effect on plasma Aβ42 and Aβ40 either at 2 weeks or at 6 weeks of administration compared to baseline levels. Plasma Aβ42 and Aβ40 levels showed large subject-to-subject variation but small variation within the same patient over the 3-sample interval. After 2 weeks of treatment with tacrine, there was a strong negative correlation between tacrine concentration and levels of Aβ42 (r = –0.64; p = 0.01) and Aβ40 (r = –0.55; p = 0.04). However, after 6 weeks there was no correlation between plasma concentrations of tacrine and Aβ42 (r = 0.33; p = 0.34) or Aβ40 (r = –0.22; p = 0.54) levels in plasma. After 2 weeks of treatment with an acetylcholinesterase inhibitor, we found a correlation between higher drug concentrations and lower β-amyloid levels. This might indicate an effect on APP metabolism with an increased α-cleavage. But after 6 weeks of drug treatment, there was no obvious drug effect on β-amyloid concentrations. This finding may indicate that compensatory mechanisms have started at 6 weeks and that no long-term effect on key pathological features in AD is to be expected by an inhibition of acetylcholinesterase.
  •  
25.
  • Berendsen, A. A. M., et al. (author)
  • Association of Adherence to a Healthy Diet with Cognitive Decline in European and American Older Adults: A Meta-Analysis within the CHANCES Consortium
  • 2017
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 43:3-4, s. 215-227
  • Journal article (peer-reviewed)abstract
    • Aim: To examine the association between a healthy diet, assessed by the Healthy Diet Indicator (HDI), and cognitive decline in older adults. Methods: Data from 21,837 participants aged >= 55 years from 3 cohorts (Survey in Europe on Nutrition and the Elderly, a Concerted Action [SENECA], Rotterdam Study [RS], Nurses' Health Study [NHS]) were analyzed. HDI scores were based on intakes of saturated fatty acids, polyunsaturated fatty acids, mono-and disaccharides, protein, cholesterol, fruits and vegetables, and fiber. The Telephone Interview for Cognitive Status in NHS and Mini-Mental State Examination in RS and SENECA were used to assess cognitive function from multiple repeated measures. Using multivariable-adjusted, mixed linear regression, mean differences in annual rates of cognitive decline by HDI quintiles were estimated. Results: Multivariable-adjusted differences in rates in the highest versus the lowest HDI quintile were 0.01 (95% CI -0.01, 0.02) in NHS, 0.00 (95% CI -0.02, 0.01) in RS, and 0.00 (95% CI -0.05, 0.05) in SENECA with a pooled estimate of 0.00 (95% CI -0.01, 0.01), I-2 = 0%. Conclusions: A higher HDI score was not related to reduced rates of cognitive decline in European and American older adults. (C) 2017 The Author(s) Published by S. Karger AG, Basel
  •  
26.
  • Berger, AK, et al. (author)
  • Negligible effects of depression on verbal and spatial performance in Alzheimer's disease
  • 2002
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 13:1, s. 1-7
  • Journal article (peer-reviewed)abstract
    • We examined whether a diagnosis of depression affects verbal and visuospatial performance in Alzheimer’s disease (AD). Using data from a population-based study, persons with AD and depression (AD/D), AD alone and a control group of normal older adults were compared in two tests of verbal ability (category and letter fluency) and two tests of visuospatial skill (block design and clock drawing). As expected, there were clear AD-related deficits across all cognitive tasks. More importantly, the AD and AD/D groups were indistinguishable on all task variables. The lack of effects of depression was discussed relative to the view that those symptoms of this disease which are especially detrimental to cognitive functioning (e.g. concentration difficulties, lack of interest, loss of energy) may already be present in AD as a result of the neurodegenerative process.
  •  
27.
  • Bjerke, Maria, 1977, et al. (author)
  • Subcortical vascular dementia biomarker pattern in mild cognitive impairment.
  • 2009
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:4, s. 348-56
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Mild cognitive impairment (MCI) is an etiologically unclear disorder. Cerebrospinal fluid (CSF) biomarkers are potentially useful for the differentiation between various MCI etiologies. AIM: The aim of the study was to assess whether baseline CSF hyperphosphorylated tau (P-tau), total tau (T-tau), amyloid beta 1-42 (Abeta(42)) and neurofilament light (NF-L) in patients with MCI could predict subcortical vascular dementia (SVD) and Alzheimer's disease (AD) at follow-up. METHODS: Biomarker levels were assessed by Luminex xMAP technology and ELISA. RESULTS: Increased baseline concentrations of NF-L significantly separated MCI-SVD from stable MCI. The MCI-SVD patients were inseparable from stable MCI but separable from patients developing AD (MCI-AD) on the basis of Abeta(42,) T-tau and P-tau(181) levels. CONCLUSION: A combination of the biomarkers Abeta(42), T-tau, P-tau(181) and NF-L has the potential to improve the clinical separation of MCI-SVD patients from stable MCI and MCI-AD patients.
  •  
28.
  •  
29.
  • Blom, Elin S., et al. (author)
  • Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype.
  • 2009
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 27:5, s. 458-64
  • Journal article (peer-reviewed)abstract
    • BACKGROUND/AIMS: Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-beta42 (Abeta42) and the apolipoprotein E gene (APOE) epsilon4 allele predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Here, we investigated these markers to assess their predictive value and influence on the rate of disease progression. METHODS: Using ELISA, we measured the CSF biomarkers in 47 AD patients, 58 patients with MCI and 35 healthy control subjects. Twenty-eight MCI patients revisited the clinic and half of them progressed to AD during a period of 3-12 years. RESULTS: The expected changes in CSF total (T)-tau, phosphorylated (P)-tau and Abeta42 levels were found in AD, confirming the diagnostic value of these biomarkers. We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon4/epsilon4 genotype, but not with decreased Abeta42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon4 homozygosity progressed faster from MCI to AD. CONCLUSIONS: CSF T-tau and P-tau as well as the APOE epsilon4/epsilon4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.
  •  
30.
  • Blomberg, M, et al. (author)
  • Cerebrospinal fluid tau levels increase with age in healthy individuals
  • 2001
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:2, s. 127-132
  • Journal article (peer-reviewed)abstract
    • Cerebrospinal fluid (CSF) tau is a promising biochemical ante-mortem marker for Alzheimer’s disease (AD). Levels are increased in AD compared to other dementias, neurological diseases and healthy controls. An age-related decrease in both soluble tau and tau bound to paired helical filaments has been shown in brains from non-demented subjects. To study tau levels in normal ageing, we investigated CSF in 29 healthy individuals aged 45–80 years. A statistically significant increase in CSF tau with increasing age was found which might be caused by neuronal loss during normal ageing and redistribution of soluble tau from the brain into CSF. We could not demonstrate any influence by the APOE genotype, though larger populations have to be investigated to confirm this result. In conclusion, we found an age-dependent increase in CSF tau in healthy individuals. We emphasise the importance of establishing an age-dependent interval of CSF tau in non-demented subjects.
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31.
  • Bogdanovic, N, et al. (author)
  • The Swedish APP670/671 Alzheimer's disease mutation: the first evidence for strikingly increased oxidative injury in the temporal inferior cortex
  • 2001
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:6, s. 364-370
  • Journal article (peer-reviewed)abstract
    • To evaluate the level of oxidative stress (OS) in familial Alzheimer’s disease (FAD), we analysed four cerebrocortical areas from patients with Swedish FAD bearing the APP670/671 mutation. The temporal inferior cortex (TIC) from Swedish FAD patients revealed a striking 2- to 3-fold increase in diene conjugates, lipid peroxides and protein carbonyls, compared to sporadic Alzheimer’s disease (AD). Compared with TIC from sporadic AD patients, the mutation carriers showed a markedly decreased activity of catalase (CAT) in the same area, and the same trend was found for another antioxidant enzyme, superoxide dismutase. These results are consistent with the deep oxidative injury of TIC in Swedish FAD. In the frontal inferior cortex (FIC), sensory postcentral cortex (SPCC) and occipital primary cortex (OPC) from Swedish FAD, the parameters of oxidative injury tended to be higher than in sporadic AD. Only the increase in the levels of lipid hydroperoxides in SPCC and of protein carbonyls in OPC was significant. Compared to sporadic AD, Swedish FAD showed a significant increase in GSSG levels and the GSSG/2GSH ratio in the FIC, SPCC and OPC. A significantly decreased activity of CAT was detectable for the SPCC and OPC in Swedish FAD. Increased OS might play a crucial role in the rapid progression of Swedish FAD from the associative temporal cortex to the primary cerebrocortical areas.
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32.
  • Borda, MG, et al. (author)
  • Timed Up and Go in People with Subjective Cognitive Decline Is Associated with Faster Cognitive Deterioration and Cortical Thickness
  • 2022
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 51:1, s. 63-72
  • Journal article (peer-reviewed)abstract
    • <b><i>Introduction:</i></b> Early markers of neurodegeneration provide an opportunity to detect, monitor, and initiate interventions in individuals who have an increased risk of developing dementia. Here, we investigated whether the Timed Up and Go (TUG) test is associated with early brain neurodegeneration and whether the TUG test could be a marker of cognitive decline in people with subjective cognitive decline (SCD). <b><i>Methods:</i></b> This is a longitudinal analysis of the Dementia Disease Initiation Study, a prospective, community-based, cohort study from Norway, designed to investigate early markers of cognitive impairment and dementia. Participants were classified as SCD and healthy controls (HC). The main studied variables were the TUG test and cognition as measured by the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer’s Disease memory composite score. Additionally, we investigated the cross-sectional association of brain morphology with the TUG using 1.5T-MRI. <b><i>Results:</i></b> The sample included 45 participants (SCD = 21, HC = 24) followed during a mean time of 1.50 ± 0.70 years. At baseline, the cognitive performance did not differ between the groups, but TUG was longer in SCD. Slower baseline TUG was associated with a faster cognitive decline in both groups and it was also associated with reduced cortical thickness especially in motor, executive, associative, and somatosensory cortical regions in people with SCD. <b><i>Discussion/Conclusion:</i></b> TUG predicted cognitive change in individuals with SCD, and there was a negative association between TUG and cortical thickness. TUG is a promising cheap and noninvasive marker of early cognitive decline and may help initiate interventions in individuals who have an increased risk of dementia.
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33.
  • Boström, Fredrik, et al. (author)
  • Cerebrospinal fluid total tau is associated with shorter survival in dementia with Lewy bodies.
  • 2009
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:4, s. 314-9
  • Journal article (peer-reviewed)abstract
    • A pathology typical of dementia with Lewy bodies (DLB) has been demonstrated to increase mortality to a greater extent than the pathology of Alzheimer's disease (AD). However, mortality in DLB has also been shown to increase with concomitant AD pathology. Furthermore, in a recent publication, we showed that there is a robust and specific increase in CSF calcium and magnesium in DLB patients compared to both AD patients and controls. Thus, in order to explore the influence of CSF AD markers and trace element concentrations on mortality in DLB, we undertook a longitudinal prospective study of 47 clinically diagnosed DLB patients and 157 AD patients as well as 49 healthy volunteers. Both AD and DLB patients showed an increased mortality compared to the healthy controls (relative risk: 10 and 8, respectively; p < 0.001). Increased levels of CSF total tau were associated with increased mortality among the DLB patients (p < 0.05), but not among the AD patients or controls. Gender, age, MMSE score, Abeta42 concentration and phosphorylated tau, and CSF trace element concentrations did not influence survival in the obtained models.
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34.
  • Bramell-Risberg, Eva, et al. (author)
  • Lower Gait Speed in Older Women with Dementia Compared with Controls.
  • 2005
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 20:5, s. 298-305
  • Journal article (peer-reviewed)abstract
    • Movement time is increased in patients with Alzheimer’s disease. <i>Objectives:</i> To study differences in movement time and ability to increase speed in older women with dementia. <i>Methods:</i> Four tests were performed at self-selected and maximal speed: walking 2 ×15 m, walking between parallel lines, ‘get up and go’ (GUG) and rising from lying supine. Twenty-two patients and 22 controls (mean ages 81 and 86 years, respectively) were included in the study. <i>Results:</i> In the groups over 80 years, walking and GUG at both speeds and rising from lying supine from the left at self-selected speed were significantly slower among patients (20–30%). Both patients and controls were able to increase movement speed when changing from self-selected to maximal speed (13–27%). Patients with Alzheimer’s disease had lower self-selected walking speed compared with patients with other types of dementia (p = 0.048). <i>Conclusion:</i> Testing physical performance in two different speeds was feasible in patients with dementia. Patients had slower gait speed and were slower in the functional tests, such as GUG, but the capacity to increase speed seemed intact.
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35.
  • Bramell-Risberg, Eva, et al. (author)
  • Slowing of Alternating Forearm Movements Is Associated with Cognitive Impairment in Community-Dwelling Older People.
  • 2010
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 29:5, s. 457-466
  • Journal article (peer-reviewed)abstract
    • Background/Aims: Motor impairment is an important aspect of cognitive decline in older adults. It has been suggested that complex motor control is affected earlier than gross motor control. The aims were to investigate if complex hand motor function was more affected than gross motor function in cognitively impaired older subjects, and to present reference values. Methods: Alternating forearm movements and grip strength were studied in 301 cases, 419 intermediates and 1,207 controls, aged 60-93 years, controlling for demographic, health-related and functional factors and comorbidity. Global cognitive function was assessed by the Mini-Mental State Examination, and episodic memory by 3-word delayed recall. Grip strength was assessed by the Grippit(R). The frequency of alternating movements during 10 s was registered electronically. Results: Alternating movements but not grip strength was associated with cognitive impairment (right: p = 0.006; left: p = 0.022). The mean alternating movements for the 70-year-old male cases compared to the controls were 2.3 versus 2.5 Hz for the right, and 2.2 versus 2.4 Hz for the left arm (p < 0.05), and for the 60-year-old women 2.0 versus 2.3 Hz for the right arm (p < 0.05). Conclusion: Complex but not gross hand motor function is associated with early cognitive impairment.
  •  
36.
  • Brane, G, et al. (author)
  • The Gottfries-Bråne-Steen scale: validity, reliability and application in anti-dementia drug trials
  • 2001
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:1, s. 1-14
  • Journal article (peer-reviewed)abstract
    • Neuropsychological investigation using a comprehensive rating scale is important for the diagnosis and evaluation of dementia patients over time. Requirements for such a scale include accuracy, reliability, sensitivity of the scale over the disease course and simplicity for clinical use by a wide range of healthcare professionals. Ideally, the scale should also be capable of assessing the impact of pharmacological and non-pharmacological treatment regimens on the management of dementia patients. The Gottfries-Bråne-Steen (GBS) Scale is a comprehensive global assessment tool for evaluating dementia symptoms and is based on a semi-structured interview and observation of the patient. The scale consists of subscales measuring intellectual (12 items), emotional (3 items) and activities of daily living, primarily items of self-care (6 items); as well as 6 items of behavioral and psychological symptoms of dementia. This review describes the reliability, validity and sensitivity of the most recent version of the GBS scale since its original publication in 1982.
  •  
37.
  • Bronge, L, et al. (author)
  • Postmortem MRI and histopathology of white matter changes in Alzheimer brains. A quantitative, comparative study
  • 2002
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 13:4, s. 205-212
  • Journal article (peer-reviewed)abstract
    • To evaluate whether magnetic resonance imaging (MRI) of white matter changes in Alzheimer’s disease either under- or overestimates the findings on neuropathology. Postmortem MRI and neuropathological examination were performed on 6 brains from elderly individuals with a postmortem diagnosis of AD. Using a specially designed brain slicer, the brains were cut corresponding to the MRI images, and stained by Luxol Fast Blue. Quantitative analysis of white matter changes on MRI and neuropathology was performed using stereological principles. Measures from MRI and pathology were highly correlated (r<sup>2</sup> = 0.71). However, pathology showed significantly more extensive changes than did MRI in all cases, with a mean of 54% larger areas. The lesions not identified with MRI represented, however, only minor changes with lower intensity of myelin staining and with an accentuation of the distance between fibres but with preserved axonal network and glial cell density.
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38.
  • Bronge, L, et al. (author)
  • White matter lesions in Alzheimer patients are influenced by apolipoprotein E genotype
  • 1999
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 10:2, s. 89-96
  • Journal article (peer-reviewed)abstract
    • To analyse the influence of apolipoprotein E (APOE) genotype on the extent of white matter lesions (WMLs) in Alzheimer’s disease (AD), we examined 60 AD patients with magnetic resonance imaging. The WMLs were rated visually in different brain regions. The patients with the APOE genotype σ4/4 had more extensive WMLs in the deep white matter than patients with genotypes σ3/3 and σ3/4. There was a correlation with age for WMLs in the deep white matter in patients with the APOE σ3/3 genotype. In patients carrying at least one σ4 allele, the WMLs showed no age correlation. The results could imply that in APOE allele σ4 carriers, the WMLs represent a pathological process related to the aetiology of the disease.
  •  
39.
  • Bronge, L, et al. (author)
  • White matter lesions in dementia: an MRI study on blood-brain barrier dysfunction
  • 2000
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 11:5, s. 263-267
  • Journal article (peer-reviewed)abstract
    • White matter lesions (WMLs) and blood-brain barrier (BBB) dysfunction are common in dementia. Both conditions may be a consequence of small-vessel disease, in which case the BBB damage would be suspected to be located to the WMLs. To further evaluate the nature of WMLs in dementia we examined 10 demented patients with WMLs, including 5 cases with elevated CSF/serum albumin ratios as an indication of BBB damage. An optimised gadolinium (Gd)-enhanced MRI technique was used including a double dose of Gd, a 30-min scan time after injection and analysis of the MR signal in the WMLs as a function over time. Results showed no significant changes in MR signal in the WMLs after contrast administration. We conclude that WMLs are not connected to BBB damage to such a degree that is detectable with this method and that the elevated CSF albumin might have another origin.
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40.
  • Brown, J, et al. (author)
  • Frontotemporal dementia linked to chromosome 3
  • 2004
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 17:4, s. 274-276
  • Journal article (peer-reviewed)abstract
    • A large pedigree with autosomal dominant frontotemporal dementia has been identified. Positional cloning has linked the disease gene to the pericentromeric region of chromosome 3. Clinical, neuropsychological, imaging, pathological and molecular genetic data are presented. The genetic mutation responsible for the disease has not been identified.
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41.
  •  
42.
  • Brännström, Benny (author)
  • Care of the delirious patient
  • 1999
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 10:5, s. 416-419
  • Journal article (peer-reviewed)abstract
    • In spite of the fact that delirium is a common and often severe cognitive disturbance in the elderly, quite few intervention studies are performed. Descriptive studies of variable quality are much more common. For example, in hip fracture patients delirium is a common complication and the cause of nursing problems that cannot be explained by the fracture per se. Nursing and medical interventions have been published separately but only one study, the Pitea Program, has so far been known that combines nursing and medical knowledge. This program has been shown to reduce the incidence of delirium in elderly hip fracture patients
  •  
43.
  • Buchhave, Peder, et al. (author)
  • Cube copying test in combination with rCBF or CSF A beta(42) predicts development of Alzheimer's disease
  • 2008
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 25:6, s. 544-552
  • Journal article (peer-reviewed)abstract
    • <i>Background/Aim: </i>The aim was to identify subjects with incipient Alzheimer’s disease (AD) among patients with mild cognitive impairment (MCI) using brief cognitive tests. <i>Methods: </i>A total of 147 MCI patients were followed for 4–6 years and the incidence of AD was 11.6%/year. At baseline, the cube copying test, clock drawing test, MMSE and measurements of regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) β-amyloid<sub>1–42</sub> (Aβ<sub>42</sub>) were performed. <i>Results: </i>The cube copying test, but not the clock drawing test, could predict AD among MCI patients with an area under the receiver operating characteristic curve of 0.64 (p < 0.01). The relative risk for future AD was increased in MCI subjects with impaired cube copying test (sex- and age-adjusted hazard ratio = 1.8, p < 0.05) and the incidence of AD was 18.2% in this subgroup. Combining the cube copying test with either rCBF or CSF Aβ<sub>42</sub> had additive effects on the risk assessment for future development of AD. MCI patients achieving high scores on both MMSE and cube copying test had a very low risk of developing AD (incidence of AD = 1.6%). <i>Conclusion: </i>In conclusion, combinations of the cube copying test with MMSE, rCBF and CSF Aβ<sub>42</sub> measurements can identify subgroups of MCI subjects with either substantially reduced or increased risk for future development of AD.
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44.
  •  
45.
  • Chen, JM, et al. (author)
  • Increased serum levels of interleukin-18, -23 and -17 in Chinese patients with Alzheimer's disease
  • 2014
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 38:5-6, s. 321-329
  • Journal article (peer-reviewed)abstract
    • <b><i>Aims:</i></b> To evaluate the serum levels of interleukin (IL)-18, IL-23 and IL-17 in Chinese patients with Alzheimer's disease (AD), and explore correlations between the three cytokines and relevant parameters. <b><i>Methods:</i></b> Serum concentrations of IL-18, IL-23 and IL-17 were measured by ELISA for 53 AD patients and 53 sex- and age-matched healthy controls in a community of elderly individuals in a Shanghai suburb. <b><i>Results:</i></b> Serum concentrations of IL-18, IL-23 and IL-17 were significantly higher in AD patients than controls. The serum level of IL-23 was observed to be significantly higher (p = 0.049) in female AD patients than male AD patients. In addition, a significantly inverse correlation was found between IL-18 and MMSE score (r<sub>s</sub> = -0.356, p = 0.011) for all AD patients. <b><i>Conclusion:</i></b> Elevated IL-18, IL-23 and IL-17 levels are observed in AD patients and differences may exist between males and females. Besides, IL-18 may correlate with the severity of AD.
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46.
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47.
  • Clerici, Francesca, et al. (author)
  • Does Vascular Burden Contribute to the Progression of Mild Cognitive Impairment to Dementia?
  • 2012
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 34:3-4, s. 235-243
  • Journal article (peer-reviewed)abstract
    • Aims: To investigate the contribution of vascular risk factors (VRFs), vascular diseases (VDs) and white matter lesions (WMLs) to the progression of mild cognitive impairment (MCI) to dementia and Alzheimer’s disease (AD). Methods: Two hundred forty-five consecutive subjects with MCI (age 74.09 ± 6.92 years) were followed for an average of 2.4 years. The Hachinski Ischemic Score and the Framingham Stroke Risk Profile were used to summarize VRFs and VDs. WMLs were graded using the Age-Related White Matter Changes Scale. Results: One hundred twenty-nine (52.6%) out of 245 subjects at risk converted to dementia, including 87 cases of AD. When hypertension occurred in MCI with deep WMLs, a 1.8-fold increased risk of dementia was observed (95% CI = 1.0–3.4). When deep WMLs occurred in MCI with high scores (≥4) on the Hachinski scale, a 3.5-fold (95% CI = 1.6–7.4) and 3.8-fold (95% CI = 1.2–11.5) risk of progression to dementia and AD was observed, respectively. Analogously, the joint effect of WMLs and high scores (≥14) on the Framingham scale nearly doubled the risk of dementia (hazard ratio = 1.9, 95% CI = 1.1–3.3). Conclusions: Accelerated progression of MCI to dementia and AD is to be expected when VRFs and VDs occur together with WMLs.
  •  
48.
  • Cova, Ilaria, et al. (author)
  • Body Mass Index Predicts Progression of Mild Cognitive Impairment to Dementia
  • 2016
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 41:3-4, s. 172-180
  • Journal article (peer-reviewed)abstract
    • Aims: To examine the relationship between body mass index (BMI) and progression to dementia and Alzheimer's disease (AD) in mild cognitive impairment (MCI). Materials and Methods: Two hundred and twenty-eight MCI subjects (mean age 74.04 +/- 6.94 years; 57% female) from a memory clinic were followed for 2.40 +/- 1.58 years. Baseline height and weight were used to calculate the BMI. The main outcome was progression to dementia (DSM-IV criteria) and AD (NINCDS-ADRDA criteria). Cox proportional hazard models were used to assess the longitudinal association of BMI with dementia and AD, adjusting for a comprehensive set of covariates, including vascular risk factors/diseases and neuroimaging profiles. Results: Out of 228 subjects with MCI, 117 (51.3%) progressed to dementia. Eighty-nine (76%) of the incident dementia cases had AD. In both unadjusted and multi-adjusted models, a higher BMI was associated with a reduced risk of dementia (multi-adjusted HR 0.9; 95% CI 0.8-0.9) and AD (multi-adjusted HR 0.9; 95% CI 0.8-0.9). Being underweight increased the risk of all types of dementia (multi-adjusted HR 2.5; 95% CI 1.2-5.1) but was not specifically associated with AD (multi-adjusted HR 2.2; 95% CI 0.9-5.3). Conclusions: BMI predicted progression of MCI to dementia and AD. In particular, a higher BMI was associated with a lower risk of dementia and AD, and underweight was associated with a higher risk of dementia. BMI assessment may improve the prognostic accuracy of MCI in clinical practice.
  •  
49.
  • Dahlrup, Beth, et al. (author)
  • Health Economic Analysis on a Psychosocial Intervention for Family Caregivers of Persons with Dementia.
  • 2014
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 37:3-4, s. 181-195
  • Journal article (peer-reviewed)abstract
    • Background/Aims: Psychosocial intervention has shown positive effects on the caregivers' burden and satisfaction. The aims of this study were to describe the cost and cost-effectiveness of such an intervention. Methods: We analyzed resource use and costs of formal care for 308 persons with dementia and their caregivers' health-related quality of life (HRQoL). Results: The costs of home help services were lower in the subgroup of spouse caregivers in the intervention group and the cost of nursing home placement was lower in the intervention group. While the person with dementia lived at home, caregivers in the intervention group reported a higher HRQoL (p < 0.01). After the person with dementia had moved to a nursing home, spouses in the control group had a lower HRQoL (p < 0.001). Conclusion: The result can be interpreted as a positive effect of the intervention focusing on the identified specific needs of the family caregivers. © 2013 S. Karger AG, Basel.
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50.
  • 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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