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Association Between Functional Performance and Alzheimer's Disease Biomarkers in Individuals Without Dementia.

ABSTRACT: OBJECTIVES:To examine the cross-sectional association between functional performance and Alzheimer's disease (AD) neuroimaging biomarkers in individuals without dementia (cognitively unimpaired (CU), and those with mild cognitive impairment (MCI)). DESIGN:Cross-sectional. SETTING:Olmsted County, Minnesota. PARTICIPANTS:Population-based Mayo Clinic Study of Aging (MCSA) participants (aged???50, mean age 71.3?±?10.2; 53.4% male; 28.3% apolipoprotein (APO)E ?4 allele carriers, 1,578 CU, 204 MCI) who underwent 11 C-Pittsburgh compound B (11 C-PiB) positron emission tomography (PET) (N=1,782). MEASUREMENTS:We defined an abnormal (high) 11 C-PiB-PET retention ratio as a standardized uptake value ratio greater than 1.42 (high amyloid; A+), abnormal (reduced) AD signature cortical thickness (neurodegeneration; N+) as less than 2.67?mm (MRI measurement), and biomarker groups according to the combination of abnormality (or not) for amyloid accumulation (A+/A-) and neurodegeneration (N+/N-). Functional performance was assessed using the Clinical Dementia Rating (CDR) Sum of Boxes (SOB) for functional domains and the Functional Activities Questionnaire (FAQ). RESULTS:Participants with a CDR-SOB (functional) score greater than 0 were almost 4 times as likely to have N?+?(odds ratio (OR)=3.92, 95% confidence interval (CI)=1.77-8.67, adjusting for age, sex, education, global cognitive z-score, and APOE ?4 allele status; p<.001) and those with a FAQ score greater than 0 were 1.5 times as likely to have A?+?(OR=1.48, 95% CI=1.04-2.11, p=.03). Higher FAQ scores were associated with greater odds of A+N?+?and A-N?+?in CU participants. CONCLUSION:The findings of this cross-sectional study supplement limited available information that supports an association between functional performance and AD neuroimaging biomarkers very early in the dementia pathophysiology. The associations should be validated in longitudinal studies. J Am Geriatr Soc 66:2274-2281, 2018.

SUBMITTER: Vassilaki M

PROVIDER: S-EPMC6391872 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Association Between Functional Performance and Alzheimer's Disease Biomarkers in Individuals Without Dementia.

Vassilaki Maria M Aakre Jeremiah A JA Kremers Walter K WK Mielke Michelle M MM Geda Yonas E YE Machulda Mary M MM Knopman David S DS Coloma Preciosa M PM Schauble Barbara B Vemuri Prashanthi P Lowe Val J VJ Jack Clifford R CR Petersen Ronald C RC Roberts Rosebud O RO

Journal of the American Geriatrics Society 20181121 12

<h4>Objectives</h4>To examine the cross-sectional association between functional performance and Alzheimer's disease (AD) neuroimaging biomarkers in individuals without dementia (cognitively unimpaired (CU), and those with mild cognitive impairment (MCI)).<h4>Design</h4>Cross-sectional.<h4>Setting</h4>Olmsted County, Minnesota.<h4>Participants</h4>Population-based Mayo Clinic Study of Aging (MCSA) participants (aged ≥ 50, mean age 71.3 ± 10.2; 53.4% male; 28.3% apolipoprotein (APO)E ε4 allele ca ...[more]

PMID: 30462843

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Project description:BackgroundApolipoprotein E epsilon 4 (APOE-ε4) carrier status is an established risk factor for Alzheimer's disease (AD) dementia. It has also been linked with sleep disturbance in healthy older adults and increased insomnia risk. This association may be driven by the effect of APOE-ε4 on AD pathological change, itself associated with sleep abnormalities. To assess this relationship, we have evaluated post-mortem neuropathological findings in patients with and without cognitive impairment and AD pathology, who had extensive clinical assessment within 12 months of death.MethodsThis retrospective cohort study used UK Brain Banks Network data. Eligible subjects were aged over 50, with pre-mortem neuropsychiatry inventory scores of sleep disturbance (NPI-K), neurocognitive testing and functional cognitive status assessment (Clinical Dementia Rating scale). Neuropathological data included Thal phase, Braak stage and CERAD scores (measures of Aβ plaque distribution, tangle distribution and neuritic plaque density, respectively) combined to form the National Institute on Aging Alzheimer's Association (NIA-AA) ABC score reflecting AD neuropathology. Participants with other significant intracerebral pathology or pathological features of non-AD dementia were excluded. Multivariate linear regression was performed with NPIK Global Score (NPIK frequency score multiplied by severity score) as the dependent variable and APOE-ε4 heterozygosity or homozygosity as independent variables. Covariates included age, gender, APOE-ε2 status and ABC NPI measures reflecting depression and anxiety. Further models stratified by ABC score and functional cognitive status were also produced.ResultsSeven hundred twenty-eight records were identified. Two hundred two participants were included in the final analysis: mean (SD) age 84.0 (9.2) and MMSE 14.0 (11.8). Mean sleep disturbance scores were highest in ε4 homozygosity (n=11), 4.55 (5.4); intermediate in ε4 heterozygosity (n=95), 2.03 (4.0); and lowest in non-ε4 carriers (n=96), 1.36 (3.3). Within the full sample, controlling for pathological status, age, gender, depression, anxiety and CDR-SOB status, APOE-ε4 homozygosity was associated with sleep disturbance (β 2.53, p=0.034). APOE-ε4 heterozygosity was similarly associated in individuals without dementia (β 1.21, p=0.048).ConclusionThese findings lend weight to the hypothesis that APOE-ε4 affects sleep by mechanisms independent of AD pathological change. Evaluation of those mechanisms would enhance understanding of sleep disturbance pathways and potentially provide treatment targets.

Project description:AimsThis study aimed to comprehensively explore the nutrition and gait of AD patients at different stages and the relationship between them.MethodsA total of 85 AD patients were consecutively enrolled in this cross-sectional study and divided into the mild cognitive impairment (MCI) due to AD (AD-MCI) and the dementia due to AD (AD-D) groups. Demographic information, nutritional status, and gait performance were compared between the two groups, and the correlation between nutritional status and gait performance was subsequently analyzed by Pearson and Spearman correlation analyses.ResultsThe AD-D group had lower scores on Mini-Nutritional Assessment (MNA) and MNAm scales, lower levels of urea nitrogen, folic acid, and vitamin B12 in blood, and higher homocysteine level than those in the AD-MCI group (all p < 0.05). The AD-D group had slower step speed, shorter step length, and shorter stride length than those in the AD-MCI group (all p < 0.05). AD patients with decreased scores of MNA and MNAm scales, and declined levels of urea nitrogen and vitamin B12 in blood had reduced gait speed and gait cadence, and prolonged step length time and stride length time, whereas homocysteine showed the almost opposite results (all p < 0.05). In the AD-MCI group, the score of scale was negatively correlated with the coefficient of variation (CV) of stride length, and the folic acid level was negatively correlated with the CV of stride length and cadence (all p < 0.05).ConclusionsAD patients at the dementia stage had worse nutritional status and gait performance than those at the MCI stage, which was associated with worse global cognition and activities of daily living. Poorer nutritional status was associated with higher gait variability in patients at the MCI stage and with poorer gait performance in patients at the dementia stage. Early identification and intervention of patients with nutritional risk or malnutrition may improve gait performance, thus reducing the risk of falling and cognitive decline, as well as the mortality.

Dataset Information

Association Between Functional Performance and Alzheimer's Disease Biomarkers in Individuals Without Dementia.

Publications

Association Between Functional Performance and Alzheimer's Disease Biomarkers in Individuals Without Dementia.

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