Dataset Information

Neurofibrillary Tangles and Conversion to Mild Cognitive Impairment with Certain Antihypertensives.

ABSTRACT: BACKGROUND:Individuals taking renin angiotensin system (RAS) acting antihypertensives exhibit slower cognitive decline and are less likely to progress from mild cognitive impairment (MCI) to Alzheimer's disease (AD), but the mechanism remains unclear. OBJECTIVE:We tested the hypothesis that individuals taking RAS acting antihypertensives exhibit less AD-related neuropathology and slower disease progression than individuals taking non-RAS acting antihypertensives. METHOD:Participants included 83 individuals with MCI who were taking an antihypertensive at baseline, had at least two follow-up visits, and had postmortem neuropathological data. Participants were old (M?=?83.1 years), 32% male, well educated (M?=?15.7 years), and 9.2% Black. RESULTS:RAS medication users (N?=?38) were less likely to progress to AD than non-RAS users (N?=?45). RAS users exhibited fewer neurofibrillary tangles than non-RAS users in the hippocampal CA1 region (p?

SUBMITTER: Wharton W

PROVIDER: S-EPMC7297195 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Neurofibrillary Tangles and Conversion to Mild Cognitive Impairment with Certain Antihypertensives.

Wharton Whitney W Zhao Liping L Steenland Kyle K Goldstein Felicia C FC Schneider Julie A JA Barnes Lisa L LL Gearing Marla M Yasar Sevil S

Journal of Alzheimer's disease : JAD 20190101 1

<h4>Background</h4>Individuals taking renin angiotensin system (RAS) acting antihypertensives exhibit slower cognitive decline and are less likely to progress from mild cognitive impairment (MCI) to Alzheimer's disease (AD), but the mechanism remains unclear.<h4>Objective</h4>We tested the hypothesis that individuals taking RAS acting antihypertensives exhibit less AD-related neuropathology and slower disease progression than individuals taking non-RAS acting antihypertensives.<h4>Method</h4>Par ...[more]

PMID: 31177216

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Project description:Multiple biomarkers can capture different facets of Alzheimer's disease. However, statistical models of biomarkers to predict outcomes in Alzheimer's rarely model nonlinear interactions between these measures. Here, we used Gaussian Processes to address this, modelling nonlinear interactions to predict progression from mild cognitive impairment (MCI) to Alzheimer's over 3 years, using Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Measures included: demographics, APOE4 genotype, CSF (amyloid-β42, total tau, phosphorylated tau), [18F ]florbetapir, hippocampal volume and brain-age. We examined: (a) the independent value of each biomarker; and (b) whether modelling nonlinear interactions between biomarkers improved predictions. Each measured added complementary information when predicting conversion to Alzheimer's. A linear model classifying stable from progressive MCI explained over half the variance (R2 = 0.51, p < .001); the strongest independently contributing biomarker was hippocampal volume (R2 = 0.13). When comparing sensitivity of different models to progressive MCI (independent biomarker models, additive models, nonlinear interaction models), we observed a significant improvement (p < .001) for various two-way interaction models. The best performing model included an interaction between amyloid-β-PET and P-tau, while accounting for hippocampal volume (sensitivity = 0.77, AUC = 0.826). Closely related biomarkers contributed uniquely to predict conversion to Alzheimer's. Nonlinear biomarker interactions were also implicated, and results showed that although for some patients adding additional biomarkers may add little value (i.e., when hippocampal volume is high), for others (i.e., with low hippocampal volume) further invasive and expensive examination may be warranted. Our framework enables visualisation of these interactions, in individual patient biomarker 'space', providing information for personalised or stratified healthcare or clinical trial design.

Project description:BackgroundIncreasing research suggests that gait abnormalities can be a risk factor for Alzheimer's Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up.MethodsFour hundred two individuals with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests.ResultsWhile controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abnormal gait (HR = 1.7), MMSE (HR = 1.09), and DSST (HR = 1.03) covariates showed a higher impact on AD dementia conversion.ConclusionsThe importance of the link between gait and related cognitive functions in terms of diagnosis, prognosis, and rehabilitation in aMCI is critical. We showed that in aMCI gait abnormalities lead to executive functions/attention deterioration and conversion to AD dementia.

Dataset Information

Neurofibrillary Tangles and Conversion to Mild Cognitive Impairment with Certain Antihypertensives.

Publications

Neurofibrillary Tangles and Conversion to Mild Cognitive Impairment with Certain Antihypertensives.

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