Dataset Information

Associations Between Brainstem Volume and Alzheimer's Disease Pathology in Middle-Aged Individuals of the Framingham Heart Study.

ABSTRACT: The brainstem is among the first regions to accumulate Alzheimer's disease (AD)-related hyperphosphorylated tau pathology during aging. We aimed to examine associations between brainstem volume and neocortical amyloid-β or tau pathology in 271 middle-aged clinically normal individuals of the Framingham Heart Study who underwent MRI and PET imaging. Lower volume of the medulla, pons, or midbrain was associated with greater neocortical amyloid burden. No associations were detected between brainstem volumes and tau deposition. Our results support the hypothesis that lower brainstem volumes are associated with initial AD-related processes and may signal preclinical AD pathology.

SUBMITTER: Jacobs HIL

PROVIDER: S-EPMC9038711 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Associations Between Brainstem Volume and Alzheimer's Disease Pathology in Middle-Aged Individuals of the Framingham Heart Study.

Jacobs Heidi I L HIL O'Donnell Adrienne A Satizabal Claudia L CL Lois Cristina C Kojis Daniel D Hanseeuw Bernard J BJ Thibault Emma E Sanchez Justin S JS Buckley Rachel F RF Yang Qiong Q DeCarli Charles C Killiany Ron R Sargurupremraj Muralidharan M Sperling Reisa A RA Johnson Keith A KA Beiser Alexa S AS Seshadri Sudha S

Journal of Alzheimer's disease : JAD 20220101 4

The brainstem is among the first regions to accumulate Alzheimer's disease (AD)-related hyperphosphorylated tau pathology during aging. We aimed to examine associations between brainstem volume and neocortical amyloid-β or tau pathology in 271 middle-aged clinically normal individuals of the Framingham Heart Study who underwent MRI and PET imaging. Lower volume of the medulla, pons, or midbrain was associated with greater neocortical amyloid burden. No associations were detected between brainste ...[more]

PMID: 35213372

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Project description:BackgroundThe digital Clock Drawing Test (dCDT) has been recently used as a more objective tool to assess cognition. However, the association between digitally obtained clock drawing features and structural neuroimaging measures has not been assessed in large population-based studies.ObjectiveWe aimed to investigate the association between dCDT features and brain volume.MethodsThis study included participants from the Framingham Heart Study who had both a dCDT and magnetic resonance imaging (MRI) scan, and were free of dementia or stroke. Linear regression models were used to assess the association between 18 dCDT composite scores (derived from 105 dCDT raw features) and brain MRI measures, including total cerebral brain volume (TCBV), cerebral white matter volume, cerebral gray matter volume, hippocampal volume, and white matter hyperintensity (WMH) volume. Classification models were also built from clinical risk factors, dCDT composite scores, and MRI measures to distinguish people with mild cognitive impairment (MCI) from those whose cognition was intact.ResultsA total of 1656 participants were included in this study (mean age 61 years, SD 13 years; 50.9% women), with 23 participants diagnosed with MCI. All dCDT composite scores were associated with TCBV after adjusting for multiple testing (P value <.05/18). Eleven dCDT composite scores were associated with cerebral white matter volume, but only 1 dCDT composite score was associated with cerebral gray matter volume. None of the dCDT composite scores was associated with hippocampal volume or WMH volume. The classification model for differentiating MCI and normal cognition participants, which incorporated age, sex, education, MRI measures, and dCDT composite scores, showed an area under the curve of 0.897.ConclusionsdCDT composite scores were significantly associated with multiple brain MRI measures in a large community-based cohort. The dCDT has the potential to be used as a cognitive assessment tool in the clinical diagnosis of MCI.

Project description:BackgroundLiver steatosis and fibrosis are emerging as risk factors for multiple extrahepatic health conditions; however, their relationship with Alzheimer's disease pathology is unclear.ObjectiveTo examine whether non-alcoholic fatty liver disease (NAFLD) and FIB-4, a non-invasive index of advanced fibrosis, are associated with brain amyloid-β (Aβ) and tau pathology.MethodsThe study sample included Framingham Study participants from the Offspring and Third generation cohorts who attended exams 9 (2011-2014) and 2 (2008-2011), respectively. Participants underwent 11C-Pittsburgh Compound-B amyloid and 18F-Flortaucipir tau positron emission tomography (PET) imaging and abdomen computed tomography, or had information on all components of the FIB-4 index. Linear regression models were used to assess the relationship of NAFLD and FIB-4 with regional tau and Aβ, adjusting for potential confounders and multiple comparisons.ResultsOf the subsample with NAFLD information (N = 169; mean age 52±9 y; 57% males), 57 (34%) had NAFLD. Of the subsample with information on liver fibrosis (N = 177; mean age 50±10 y; 51% males), 34 (19%) had advanced fibrosis (FIB-4 > 1.3). Prevalent NAFLD was not associated with Aβ or tau PET. However, FIB-4 index was significantly associated with increased rhinal tau (β= 1.03±0.33, p = 0.002). Among individuals with prevalent NAFLD, FIB-4 was related to inferior temporal, parahippocampal gyrus, entorhinal and rhinal tau (β= 2.01±0.47, p < 0.001; β= 1.60±0.53, p = 0.007, and β= 1.59±0.47, p = 0.003 and β= 1.60±0.42, p = 0.001, respectively) and to Aβ deposition overall and in the inferior temporal and parahippocampal regions (β= 1.93±0.47, p < 0.001; β= 1.59±0.38, p < 0.001, and β= 1.52±0.54, p = 0.008, respectively).ConclusionThis study suggests a possible association between liver fibrosis and early Alzheimer's disease pathology, independently of cardio-metabolic risk factors.

Dataset Information

Associations Between Brainstem Volume and Alzheimer's Disease Pathology in Middle-Aged Individuals of the Framingham Heart Study.

Publications

Associations Between Brainstem Volume and Alzheimer's Disease Pathology in Middle-Aged Individuals of the Framingham Heart Study.

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