| 1. |
- Chincarini, Andrea, et al.
(författare)
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Automatic temporal lobe atrophy assessment in prodromal AD: Data from the DESCRIPA study
- 2014
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5279 .- 1552-5260. ; 10:4, s. 456-467
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the framework of the clinical validation of research tools, this investigation presents a validation study of an automatic medial temporal lobe atrophy measure that is applied to a naturalistic population sampled from memory clinic patients across Europe. Methods: The procedure was developed on 1.5-T magnetic resonance images from the Alzheimer's Disease Neuroimaging Initiative database, and it was validated on an independent data set coming from the DESCRIPA study. All images underwent an automatic processing procedure to assess tissue atrophy that was targeted at the hippocampal region. For each subject, the procedure returns a classification index. Once provided with the clinical assessment at baseline and follow-up, subjects were grouped into cohorts to assess classification performance. Each cohort was divided into converters (co) and nonconverters (nc) depending on the clinical outcome at follow-up visit. Results: We found the area under the receiver operating characteristic curve (AUC) was 0.81 for all co versus nc subjects, and AUC was 0.90 for subjective memory complaint (SMCnc) versus all co subjects. Furthermore, when training on mild cognitive impairment (MCI-nc/MCI-co), the classification performance generally exceeds that found when training on controls versus Alzheimer's disease (CTRL/AD). Conclusions: Automatic magnetic resonance imaging analysis may assist clinical classification of subjects in a memory clinic setting even when images are not specifically acquired for automatic analysis. (C) 2014 The Alzheimer's Association. All rights reserved.
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| 2. |
- Elobeid, Adila, et al.
(författare)
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Alzheimer's disease-related plaques in nondemented subjects
- 2014
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 10:5, s. 522-529
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) pathology was assessed in 587 nondemented subjects, with age at death at or more than 50 years. In 307 subjects, amyloid-beta (A beta) immunoreactive (IR) plaques were seen; in 192 subjects, neuritic plaques (NPs) stained with modified Bielschowsky silver stain (mBky) were observed. In 20% of the whole cohort and in 62% of the 192 subjects with NPs in mBky, hyperphosphorylated tau (HPtau) IR NPs were seen. In most cases in this nondemented cohort, the HPtau IR NPs were observed either sparsely or to a moderate extent. The correlation between the NP score and Braak stage was best (r = 0.6, P < .001) when HPtau immunohistochemistry was used. Eighty-three percent of the subjects could not be categorized following the 1997 National Institute on Aging and the Reagan Institute (NIA-RI) recommendations, whereas the 2012 National Institute on Aging Alzheimer's Association (NIA-AA) guidelines were applicable for all study subjects. Twenty-eight subjects had an intermediate level of AD neuropathological change according to the 2012 NIA-AA guidelines, and 25 of these 28 subjects displayed HPtau IR NPs in the temporal cortex. It is noteworthy, however, that as many as 119 out of the 192 subjects with NPs in mBky displayed HPtau IR NPs in the temporal cortex. Ninety-four of these 119 subjects with neocortical HPtau IR NPs had a low level of neuropathological AD change according to the 2012 NIA-AA guidelines because they were in Braak stages I and II. Thus, 94 subjects were not acknowledged as being at risk for AD when applying the 2012 NIA-AA guidelines. We suggest that to identify all subjects with cortical HPtau pathology and, consequently, probably being at risk for developing AD, in addition to the level of AD neuropathological change as recommended by the 2012 NIA-AA guidelines, assessment of HPtau IR NPs in the neocortex should be carried out.
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| 3. |
- Hagman, Göran, et al.
(författare)
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Midlife hopelessness and white matter lesions two decades later : A population-based study
- 2010
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 7:4, Supplement, s. 595-595
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hopelessness has been associated with increased cardiovas- cular disease mortality and morbidity, subclinical atherosclerosis and meta- bolic syndrome. This study investigates the relation between midlife hopelessness and white matter lesions (WMLs) 20 years later in a Finnish population of men and women. Methods: Participants of the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) study in Finland were derived from random, population-based samples previously surveyed in 1972,1977, 1982 or 1987. In 1998, 1449 (73%) individuals aged 65-79 years participated in the re-examination. A subgroup (n1⁄4112, including 39 dementia cases, 31 mild cognitive impairment (MCI) cases and 42 con- trols) underwent 1.5T MRI scanning at re-examination, and WMLs were as- sessed from FLAIR-images using a semi-quantitative visual rating scale. Hopelessness was measured by 2 questionnaire items (expectations about future and reaching goals). Results: Subjects with increased hopelessness had a significantly higher risk of developing more severe WMLs two de- cades later. OR (95% CI) was 4.35 (1.36-13.46) in ordinal regression anal- yses adjusted for age, sex education, follow-up time, presence of the APOEe4 allele, systolic blood pressure, BMI, history of stroke, heart infarct, smoking and level of midlife leisure physical activity. Conclusions: Higher levels of hopelessness at midlife seem to be related to more severe WMLs later in life. Since WMLs may contribute to late-life cognitive impairment, lifestyle management of midlife vascular risk factors (which also increase the risk of dementia and cognitive impairment) may have better effects if people’s expectations are more thoroughly discussed.
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| 4. |
- Handels, Ron L. H., et al.
(författare)
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Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers
- 2017
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 13:8, s. 903-912
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia.METHODS: The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers.RESULTS: Adding CSF improved predictive accuracy with 0.11 (scale from 0-1). Of all participants, 136 (54%) had a change in risk score of 0.10 or higher (which was considered clinically relevant), of whom in 101, it was in agreement with their dementia status at follow-up.DISCUSSION: An individual person's risk of progression from MCI to dementia can be improved by relying on CSF biomarkers in addition to recommended clinical and imaging tests for usual care.
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| 5. |
- Herukka, Sanna-Kaisa, et al.
(författare)
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Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment.
- 2017
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 13:3, s. 285-295
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Tidskriftsartikel (refereegranskat)abstract
- This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3) interpretation of results, and 4) patient counseling. The working group recommended using CSF AD biomarkers in the diagnostic workup of MCI patients, after prebiomarker counseling, as an add-on to clinical evaluation to predict functional decline or conversion to AD dementia and to guide disease management. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Furthermore, the working group provided recommendations for interpretation of ambiguous CSF biomarker results and for pre- and post-biomarker counseling.
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| 6. |
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| 7. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 8. |
- Kivipelto, Miia, et al.
(författare)
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The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) : Study design and progress
- 2013
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 9:6, s. 657-665
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Tidskriftsartikel (refereegranskat)abstract
- Background: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi-center, randomized, controlled trial ongoing in Finland. Materials: Participants (1200 individuals at risk of cognitive decline) are recruited from previous population-based non-intervention studies. Inclusion criteria are CAIDE Dementia Risk Score >= 6 and cognitive performance at the mean level or slightly lower than expected for age (but not substantial impairment) assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. The 2-year multidomain intervention consists of: nutritional guidance; exercise; cognitive training and social activity; and management of metabolic and vascular risk factors. Persons in the control group receive regular health advice. The primary outcome is cognitive performance as measured by the modified Neuropsychological Test Battery, Stroop test, and Trail Making Test. Main secondary outcomes are: dementia (after extended follow-up); disability; depressive symptoms; vascular risk factors and outcomes; quality of life; utilization of health resources; and neuroimaging measures. Results: Screening began in September 2009 and was completed in December 2011. All 1200 persons are enrolled and the intervention is ongoing as planned. Baseline clinical characteristics indicate that several vascular risk factors and unhealthy lifestyle related factors are present, creating a window of opportunity for prevention. The intervention will be completed during 2014. Conclusions: The FINGER is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia.
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| 9. |
- Kivipelto, Miia, et al.
(författare)
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World-Wide FINGERS Network : A global approach to risk reduction and prevention of dementia
- 2020
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:7, s. 1078-1094
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Tidskriftsartikel (refereegranskat)abstract
- Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.
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| 10. |
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