Mielke, Michelle M

Objectives To determine the cross‐sectional association between cerebral amyloid‐beta (A β ) deposition and gait. Design Cross‐sectional. Setting Population‐based cohort study in Olmsted County, MN . Participants Cognitively normal individuals (n = 611), aged 50 to 69 years, enrolled in the Mayo Clinic Study of Aging with concurrent PiB‐ PET imaging and gait assessment. Participants with a history of stroke, alcoholism, Parkinson's disease, subdural hematoma, traumatic brain injury, or normal pressure hydrocephalus were excluded. Measurements PiB‐ PET SUVR was measured in prefrontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate, and motor‐specific regions of interest ( ROI s). Gait parameters (speed, cadence, stride length, double support time, and intra‐individual stance time variability) were measured using GAITR ite ® instrumentation. Linear regression models were adjusted for age, sex, body mass index, education, APOE ε 4 allele, Charlson comorbidity index, and depression. In secondary analyses, we additionally adjusted for neurodegeneration (hippocampal volume, FDG PET SUVR , and cortical thickness) in AD ‐associated regions. Results In fully adjusted models including neuroimaging measures of neurodegeneration, higher PiB‐ PET SUVR across all ROI s was associated with slower gait speed ( P < .05 except for the parietal ROI ), lower cadence and longer double support time ( P ≤ .05 except for the motor ROI ), and greater stance time variability ( P < .05). In sex‐stratified analyses, the association between higher PiB‐ PET SUVR across all ROI s and measures of gait was only present among women. Conclusion PiB‐ PET SUVR across ROI s, independent of general measures of AD ‐associated neurodegeneration, is associated with poorer performance on multiple gait parameters among cognitively normal women, aged 50 to 69 years. Longitudinal studies are needed to determine whether A β predicts gait decline in both women and men.

Objectives To investigate the timing (mid‐ vs late life) of physical activity, apolipoprotein ( APO )E ε 4, and risk of incident mild cognitive impairment ( MCI ). Design Prospective cohort study. Setting Mayo Clinic Study of Aging (Olmsted County, MN ). Participants Cognitively normal elderly adults (N = 1,830, median age 78, 50.2% female). Measurements Light, moderate, and vigorous physical activities in mid‐ and late life were assessed using a validated questionnaire. An expert consensus panel measured MCI based on published criteria. Cox proportional hazards models were used to calculate hazard ratios ( HR s) and 95% confidence intervals ( CI s) with age as a time scale after adjusting for sex, education, medical comorbidity, and depression. Results Light ( HR = 0.58, 95% CI = 0.43–0.79) and vigorous ( HR = 0.78, 95% CI = 0.63–0.97) physical activity in midlife were associated with lower risk of incident MCI . The association between moderate activity and incident MCI was not significant ( HR = 0.85, 95% CI = 0.67–1.09). In late life, light ( HR = 0.75, 95% CI = 0.58–0.97) and moderate ( HR = 0.81, 95% CI = 0.66–0.99) but not vigorous physical activity were associated with lower risk of incident MCI . A synergistic interaction was also observed between mid‐ and late‐life activity in reducing risk of incident MCI . Furthermore, APOE ε 4 carriers who did not exercise had a higher risk of incident MCI than noncarriers who reported physical activity. Conclusion Physical activity reduced the risk of incident MCI . Exercising in mid‐ and late life had an additive synergistic interaction in reducing the risk of MCI .

Abstract Introduction Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro‐deoxyglucose (FDG) PET, and MRI cortical thickness. Methods We examined five methods for determining cut points. Results The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age‐matched CN method labeled fewer people abnormal. Discussion In the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age‐matched CN method.

Abstract More than 5 million Americans are living with Alzheimer's disease (AD) today, and nearly two‐thirds of Americans with AD are women. This sex difference may be due to the higher longevity women generally experience; however, increasing evidence suggests that longevity alone is not a sufficient explanation and there may be other factors at play. The Alzheimer's Association convened an expert think tank to focus on the state of the science and level of evidence around gender and biological sex differences for AD, including the knowledge gaps and areas of science that need to be more fully addressed. This article summarizes the think tank discussion, moving forward a research agenda and funding program to better understand the biological underpinnings of sex‐ and gender‐related disparities of risk for AD.

Background: Previous studies reported that slower gait speed might predict cognitive impairment and dementing illnesses, supporting the role of gait speed as a possible subclinical marker of cognitive impairment. However, the predictive value of other gait parameters for cognitive decline is unclear. Objective: To investigate and compare the association with, and prediction of, specific gait parameters for cognition in a population-based sample. Methods: The analysis included 3,426 cognitively normal participants enrolled in the Mayo Clinic Study of Aging. At baseline and every 15 months (mean follow-up = 1.93 years), participants had a study coordinator evaluation, neurological examination, and a neuropsychological assessment using nine tests that covered four domains. Gait parameters were assessed with the GAITRite ® instrument. General linear mixed effects models were used to compute the annualized rate of change in cognitive domain z-scores, controlling for age, sex, education, depression, comorbidities, body mass index, APOE ɛ 4 allele, and visit number, and excluding individuals with a history of stroke, alcoholism, Parkinson’s disease, subdural hematoma, and normal pressure hydrocephalus. Results: Spatial (stride length), temporal (ambulatory time, gait speed, step count, cadence, double support time), and spatiotemporal (cadence) gait parameters, and greater intraindividual variability in stride length, swing time, and stance time were associated with a significant decline in global cognition and in specific domains including memory, executive function, visuospatial, and language. Conclusions: Spatial, temporal, and spatiotemporal measures of gait and greater variability of gait parameters were associated with and predictive of both global- and domain-specific cognitive decline.

AbstractIntroductionThe Mediterranean diet (MeDi) is associated with reduced risk of cognitive impairment, but it is unclear whether it is associated with better brain imaging biomarkers.MethodsAmong 672 cognitively normal participants (mean age, 79.8 years, 52.5% men), we investigated associations of MeDi score and MeDi components with magnetic resonance imaging measures of cortical thickness for the four lobes separately and averaged (average lobar).ResultsHigher MeDi score was associated with larger frontal, parietal, occipital, and average lobar cortical thickness. Higher legume and fish intakes were associated with larger cortical thickness: legumes with larger superior parietal, inferior parietal, precuneus, parietal, occipital, lingual, and fish with larger precuneus, superior parietal, posterior cingulate, parietal, and inferior parietal. Higher carbohydrate and sugar intakes were associated with lower entorhinal cortical thickness.DiscussionIn this sample of elderly persons, higher adherence to MeDi was associated with larger cortical thickness. These cross‐sectional findings require validation in prospective studies.

Abstract Introduction Tau protein levels in plasma may be a marker of neuronal damage. We examined associations between plasma tau levels and Alzheimer's disease (AD)–related magnetic resonance imaging (MRI) and positron emission tomography (PET) neuroimaging measures among nondemented individuals. Methods Participants included 378 cognitively normal (CN) and 161 mild cognitive impairment (MCI) individuals enrolled in the Mayo Clinic Study of Aging with concurrent neuropsychological measures and amyloid PET, fluorodeoxyglucose PET, and MRI. Baseline plasma tau levels were measured using the Quanterix Simoa‐HD1 tau assay. Results Plasma tau levels were higher in MCI compared with CN (4.34 vs. 4.14 pg/mL, P = .078). In regression models adjusted for age, gender, education, and APOE , higher plasma tau was associated with worse memory performance (b = −0.30, P = .02) and abnormal cortical thickness in an AD signature region (odds ratio = 1.80, P = .018). Discussion Plasma tau is associated with cortical thickness and memory performance. Longitudinal studies will better elucidate the associations between plasma tau, neurodegeneration, and cognition.