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  • Besser, L. M., et al. (författare)
  • Body mass index, weight change, and clinical progression in mild cognitive impairment and alzheimer disease
  • 2014
  • Ingår i: Alzheimer Disease and Associated Disorders. - 0893-0341. ; 28:1, s. 36-43
  • Tidskriftsartikel (refereegranskat)abstract
    • The speed and severity of clinical progression after Alzheimer disease (AD) diagnosis varies and depends on multiple factors, most not well elucidated. We assessed whether body mass index (BMI) and 1-year weight change (WC) are associated with clinical progression in amnestic mild cognitive impairment (aMCI) and early-stage AD. Longitudinal data comprising 2268 aMCI and 1506 AD participants in the National Alzheimer's Coordinating Center's Uniform Data Set were used to examine nuances of clinical progression by BMI and WC, as well as potential variations in associations by age, sex, BMI (WC model), or apolipoprotein E genotype. In aMCI, high BMI (vs. moderate BMI) was associated with slower progression; weight loss (vs. no WC) was associated with faster progression. In AD, no significant differences were observed in clinical progression by BMI or WC. The association between BMI and clinical progression varied significantly by apolipoprotein E genotype in AD, and the association between WC and clinical progression varied significantly by sex and BMI in aMCI. Baseline BMI and 1-year WC in late life may serve as early prognostic indicators in aMCI and early-stage AD. If replicated, these results may help in counseling patients on anticipated clinical progression and suggest windows of opportunity for intervention.
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  • Brun, Arne (författare)
  • Identification and characterization of frontal lobe degeneration - Historical perspective on the development of FTD
  • 2007
  • Ingår i: Alzheimer Disease and Associated Disorders. - 0893-0341. ; 21:4, s. 3-4
  • Tidskriftsartikel (refereegranskat)abstract
    • This is a historical account of the development of the concept frontotemporal dementia, beginning with our discovery in the late 60s of a simple degenerative form. It was named frontal lobe degeneration of non-Alzheimer type to clearly separate it from the then almost totally dominating diagnosis Alzheimer disease. In the absence of immunohistochemical methods for specific disease markers, we had to rely solely on structural features. Later, from the 80s, the successively introduced methods to show glial acidic protein, tau, synaptophysin, ubiquitin, and other markers confirmed our impression of a simple type of degeneration. These methods also added further forms with additional features, and from the 90s genetics has contributed new disease characteristics, all these advances leading up to the present conceptual structure of frontotemporal lobar degeneration.
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  • Elmståhl, Sölve, et al. (författare)
  • How should a group living unit for demented elderly be designed to decrease psychiatric symptoms?
  • 1997
  • Ingår i: Alzheimer Disease and Associated Disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341. ; 11:1, s. 47-52
  • Tidskriftsartikel (refereegranskat)abstract
    • The main objectives were to study relationships between the design of group living (GL) units and psychiatric symptoms in demented patients before, 6 months after, and 1 year after admission to GL units. The study population comprised 105 demented elderly (83 ± 6 years), 37% with dementia of Alzheimer's type and 58% with vascular dementia. The patients were relocated by the municipal care planning team after clinical examination. An observational scale (the Organic Brain Syndrome scale) was used to assess confusional symptoms and disorientation. The physical environment was assessed by an architect using the Therapeutic Environment Screening Scale, which evaluates general design, space, lighting, noise, communication area, floor plan, and related factors. Less than 15% of the patients had no signs of dyspraxia, hallucinosis, dysphasia, or depression at admission, whereas 66% or more reported lack of vitality, aggressiveness, or restlessness. Fourteen out of 18 units had a corridor-like design (group A), one unit an L-shaped design (group B), and the others a square or H-shaped design (group C). Patients living in the B unit had less disorientation than the others at the 6-month follow-up. After 1 year, the patients in the A units had more dyspraxia, lack of vitality, and disorientation of identity. The communication areas in the units were negatively associated with 'disorientation for recent memory' and 'lack of vitality,' adjusted for type of dementia (r = -0.13 to -0.16). The size of the activity area, indoor public rooms in square meters, was not correlated to confusional reactions and disorientation. In conclusion, a GL unit design that facilitates perception without reducing the communication area is to be preferred.
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  • Frisoni, GB, et al. (författare)
  • The predementia diagnosis of Alzheimer disease
  • 2004
  • Ingår i: Alzheimer disease and associated disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341. ; 18:2, s. 51-53
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Ganguli, M., et al. (författare)
  • Population Neuroscience: Dementia Epidemiology Serving Precision Medicine and Population Health
  • 2018
  • Ingår i: Alzheimer Disease and Associated Disorders. - 0893-0341. ; 32:1, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Over recent decades, epidemiology has made significant contributions to our understanding of dementia, translating scientific discoveries into population health. Here, we propose reframing dementia epidemiology as "population neuroscience," blending techniques and models from contemporary neuroscience with those of epidemiology and biostatistics. On the basis of emerging evidence and newer paradigms and methods, population neuroscience will minimize the bias typical of traditional clinical research, identify the relatively homogenous subgroups that comprise the general population, and investigate broader and denser phenotypes of dementia and cognitive impairment. Long-term follow-up of sufficiently large study cohorts will allow the identification of cohort effects and critical windows of exposure. Molecular epidemiology and omics will allow us to unravel the key distinctions within and among subgroups and better understand individuals' risk profiles. Interventional epidemiology will allow us to identify the different subgroups that respond to different treatment/prevention strategies. These strategies will inform precision medicine. In addition, insights into interactions between disease biology, personal and environmental factors, and social determinants of health will allow us to measure and track disease in communities and improve population health. By placing neuroscience within a real-world context, population neuroscience can fulfill its potential to serve both precision medicine and population health. © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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  • Gatz, M, et al. (författare)
  • Lifestyle risk and delaying factors
  • 2006
  • Ingår i: Alzheimer disease and associated disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341. ; 20:33 Suppl 2, s. S84-S88
  • Tidskriftsartikel (refereegranskat)
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  • Gorelick, PB, et al. (författare)
  • Prevention of vascular dementia
  • 1999
  • Ingår i: Alzheimer disease and associated disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341. ; 1313 Suppl 3, s. S131-S139
  • Tidskriftsartikel (refereegranskat)
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  • Jonhagen, ME (författare)
  • Nerve growth factor treatment in dementia
  • 2000
  • Ingår i: Alzheimer disease and associated disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341. ; 1414 Suppl 1, s. S31-S38
  • Tidskriftsartikel (refereegranskat)
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  • Jönsson, Linus, et al. (författare)
  • Patient- and proxy-reported utility in Alzheimer disease using the EuroQoL
  • 2006
  • Ingår i: Alzheimer Disease and Associated Disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341 .- 1546-4156. ; 20:1, s. 49-55
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aims to compare patient- and proxy-rated utilities and health-related quality of life from individuals in different stages of Alzheimer disease (AD). Two hundred seventy-two patients and their primary caregivers were enrolled in a prospective observational study and underwent three consecutive interviews, 6 months apart. Average Mini-Mental State Examination (MMSE) scores were 19.3, 18.0, and 16.4 at the three interviews; scores ranged from 0 to 30. Using the EuroQoL EQ-5D instrument, patient-rated health utilities were on average 0.833 with little variation across MMSE-based severity levels. Proxy-rated health utilities were 0.69 (MMSE >25), 0.64 (MMSE 21-25), 0.50 (MMSE 15-20), 0.49 (MMSE 10-14), and 0.33 (MMSE <10). Proxy-rated utilities, as well as changes in utilities over time, were significantly related to MMSE scores and inversely related to scores on a brief version of the neuropsychiatric inventory (NPI) and institutionalization. Utilities were highly correlated with the disease-specific quality of life instrument QoL-AD. The study shows that the EuroQoL can be used to rate utilities in Alzheimer disease, but there are important differences between patient- and proxy-ratings.
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  • Jönsson, Linus, et al. (författare)
  • Second International Pharmacoeconomic Conference on Alzheimer's Disease
  • 2000
  • Ingår i: Alzheimer disease and associated disorders. - : Ovid Technologies (Wolters Kluwer Health). - 1546-4156 .- 0893-0341. ; 14:3, s. 137-140
  • Tidskriftsartikel (refereegranskat)abstract
    • The Second International Pharmacoeconomic Conference on Alzheimer's Disease was held in Stockholm, Sweden, on April 4, 2000. The presentations focused on the role of cognition in pharmacoeconomic evaluations, the costs and consequences of behavioral disturbances, quality of life, disease progression models, and methods for valuing informal care. The results from individual studies will be published separately. Cognition has been used as the sole measure of disease severity in economic evaluations in dementia. However, behavioral disturbances are an important determinant of both cost and quality of life and should also be considered when appraising the effect of treatment. Quality-of-life assessment constitutes a single measure of the total impact of the disease, as well as a way of quantifying the benefits of treatment with antidementia drugs so that they can be compared with interventions in other disease areas. Measuring the quality of life of patients with dementia is associated with methodologic difficulties related to the difficulties for some patients in completing usual assessment processes. Disease progression models may be helpful in extrapolating the results from clinical trials to longer time periods and more representative populations. Modeling is an unavoidable part of the economic evaluation of antidementia drugs, and efforts should be made to increase transparency and comparability among models. Informal care constitutes a large percentage of the total care for patients with dementia, and the valuation of these services has a large impact on the results of pharmacoeconomic evaluations. Difficulties lie in quantifying the time spent on caring for the elderly and in attaching the correct price to each unit of time. The contingent valuation method is an alternative way of valuing informal care that so far has not been used in the field of dementia.
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  • Lundberg, C, et al. (författare)
  • Dementia and driving: an attempt at consensus
  • 1997
  • Ingår i: Alzheimer disease and associated disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341. ; 11:1, s. 28-37
  • Tidskriftsartikel (refereegranskat)
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  • Marcusson, Jan, 1958-, et al. (författare)
  • Galantamine demonstrates efficacy and safety in elderly patients with Alzheimer disease
  • 2003
  • Ingår i: Alzheimer Disease and Associated Disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341 .- 1546-4156. ; 17:SUPPL. 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer disease (AD) treatment guidelines state that cholinergic agents are not cost-effective in patients with more severe disease. Because many physicians may deem an older patient unlikely to respond to treatment, older AD patients may remain untreated. Galantamine (Reminyl), a novel cholinergic agent, is effective in mild to moderate AD. This post hoc analysis of pooled phase III galantamine clinical trials was designed to assess whether older (=80 years) and younger (=79 years) AD patients experience similar benefits with galantamine based on changes in the ADAS-cog and CIBIC-plus. Mean ADAS-cog scores for older patients treated with galantamine 24 mg/day significantly improved versus baseline and versus placebo at month 3. Cognitive improvement was maintained versus placebo at month 6, the ADAS-cog score for placebo patients dropped below baseline at month 6. Change in CIBIC-plus for galantamine was significantly different from placebo at months 5 to 6. Mean ADAS-cog score in older patients taking galantamine for 12 months remained above baseline. The score for patients taking placebo for 6 months before switching to galantamine did not differ significantly from baseline at 12 months but was lower than in patients receiving galantamine for 12 months. Incidence of adverse events in patients > 80 years was similar to that in the overall study population. Galantamine maintained cognitive and global function in patients > 80 years with mild to moderate AD for at least 5 to 6 months and cognitive efficacy for 12 months. Prescribing approved therapies such as galantamine for older patients with AD is recommended.
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  • Nordberg, Agneta, et al. (författare)
  • Kinetic analysis of regional (S)(-)11C-nicotine binding in normal and Alzheimer brain : In vivo assessment using positron emission tomography
  • 1995
  • Ingår i: Alzheimer Disease and Associated Disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341 .- 1546-4156. ; 9:1, s. 21-27
  • Tidskriftsartikel (refereegranskat)abstract
    • A compartment model has been developed and validated for the kinetic analysis of (S)(-)11C-nicotine binding in the brain including a compensation for the influence of regional cerebral blood flow (rCBF). The model was applied to eight patients with Alzheimer disease (AD) and three age-matched healthy volunteers who received intravenous injections of (S)(-)11C-nicotine and 11C-butanol. The uptake and time course of radioactivity in different brain regions were assessed by positron emission tomography (PET). The rate constant k2* was formulated by dividing the K2 rate constant for 11C-nicotine with the K1 rate constant for 11C-butanol and thereby minimizing the influence of CBF on the quantitated binding of 11C-nicotine. The rate constant k2* for 11C-nicotine giving a quantitative measure of binding in the brain tissue was significantly higher in the temporal and frontal cortices as well as in the hippocampus of AD brains as compared with controls, indicating deficits in specific nicotinic binding in these brain areas of AD patients. A significant and negative correlation was obtained between cognitive function (Mini-Mental State Examination) and k2* of 11C-nicotine in the temporal and frontal cortices as well as in the hippocampus. The described kinetic model allowed in vivo quantification of nicotinic receptor binding in brain, which will be of importance in the future for evaluation of diagnosis, progress of disease, as well as the therapeutic effects in the treatment of AD.
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  • Passant, Ulla, et al. (författare)
  • Psychiatric Symptoms and Their Psychosocial Consequences in Frontotemporal Dementia.
  • 2005
  • Ingår i: Alzheimer Disease and Associated Disorders. - 0893-0341. ; 19 Suppl 1, s. 15-18
  • Tidskriftsartikel (refereegranskat)abstract
    • Based on a retrospective study of 19 neuropathologically verified cases with frontotemporal dementia (FTD), neuropsychiatric symptoms related to behavioral disturbances and their psychosocial consequences were studied. The results indicate that frontotemporal dementia is often misdiagnosed early in the clinical course. Behavioural features with impaired social interactions, impaired personal regulation, and loss of insight were seen in all patients. The psychosocial consequences reported in this paper challenge future research in frontotemporal dementia.
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  • Sachdev, P.S., et al. (författare)
  • Diagnostic criteria for vascular cognitive disorders: A VASCOG statement
  • 2014
  • Ingår i: Alzheimer Disease and Associated Disorders. - 0893-0341. ; 28:3, s. 206-218
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:: Several sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination. METHODS:: Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the fifth revision of Diagnostic and Statistical Manual (DSM-5) Task Force. RESULTS:: Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent cooccurrence of Alzheimer disease pathology emphasized. CONCLUSIONS:: The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved. © 2014 by Lippincott Williams and Wilkins.
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  • Santillo, Alexander, et al. (författare)
  • Frontotemporal Dementia-amyotrophic Lateral Sclerosis Complex is Simulated by Neurodegeneration With Brain Iron Accumulation
  • 2009
  • Ingår i: Alzheimer Disease and Associated Disorders. - 0893-0341 .- 1546-4156. ; 23:3, s. 298-300
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe a case of late onset neurodegeneration with brain iron accumulation (NBIA) presenting as frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS). A male patient presented at age 66 with change of personality: disinhibition, emotional blunting, and socially inappropriate behavior, coupled with dysarthria, dystonia, and corticospinal tract involvement. Magnetic resonance imaging showed general cortical atrophy, iron deposits in the globus pallidus, and the "eye of the tiger" sign. Neuropsychologic performance was globally reduced, especially executive functions. Fluorodeoxyglucose positron emission tomography showed hypometabolism predominantly in frontal and temporal areas. Repeated neurophysiologic examinations showed signs of chronic denervation. The patient was diagnosed with NBIA but fulfilled consensus criteria for FTD and had a clinical picture of ALS, without neurophysiologic confirmation. Our finding introduces NBIA as a possible cause of FTD and as a differential diagnosis of the FTD-ALS complex.
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  • Skoglund, Lena, et al. (författare)
  • Novel Progranulin Mutation Detected in 2 Patients With FTLD
  • 2011
  • Ingår i: Alzheimer Disease and Associated Disorders. - : Lippincott Williams & Wilkins. - 0893-0341 .- 1546-4156. ; 25:2, s. 173-178
  • Tidskriftsartikel (refereegranskat)abstract
    • Frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions, and linkage to chromosome 17 was recently found to be caused by mutations in the progranulin (PGRN) gene. In this study, we screened a group of 51 FTLD patients for PGRN mutations and identified a novel exon 6 splice donor site deletion (IVS6+5_8delGTGA) in 2 unrelated patients. This mutation displayed an altered splicing pattern generating 2 aberrant transcripts and causing frameshifts of the coding sequence, premature termination codons, and a near absence of PGRN mRNA from the mutated alleles most likely through nonsense-mediated decay. The subsequent PGRN haploinsufficiency is consistent with previously described PGRN mutations. We present a molecular characterization of the IVS6+5_8delGTGA mutation and also describe clinical and neuropathologic features from the 2 patients carrying this PGRN mutation. From the screening of these 51 FTLD patients, we could also identify the earlier reported mutation Gln130fs, and several coding sequence variants that are most likely nonpathogenic.
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  • Wimo, Anders, et al. (författare)
  • The magnitude of dementia occurrence in the world
  • 2003
  • Ingår i: Alzheimer Disease and Associated Disorders. - : Lippincott Williams & Wilkins. - 0893-0341 .- 1546-4156. ; 17:2, s. 63-67
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, the worldwide occurrence of dementia in 2000 and during the period 1950–2050 was estimated. The calculations were based on worldwide demographics of the elderly and age‐specific prevalence and incidence values of dementia, estimated from a meta‐analysis. In a sensitivity analysis, different prevalence sources were used. The worldwide number of persons with dementia in 2000 was estimated at about 25 million persons. Almost half of the demented persons (46%) lived in Asia, 30% in Europe, and 12% in North America. Fifty‐two percent lived in less developed regions. About 6.1% of the population 65 years of age and older suffered from dementia (about 0.5% of the worldwide population) and 59% were female. The number of new cases of dementia in 2000 was estimated to be 4.6 million. The forecast indicated a considerable increase in the number of demented elderly from 25 million in the year 2000 to 63 million in 2030 (41 million in less developed regions) and to 114 million in 2050 (84 million in less developed regions). In conclusion, the majority of demented elders live in less developed regions, and this proportion will increase considerably in the future.
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