Hagen, Clinton E.

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.

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.

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.

AbstractIntroductionFew studies have examined the effects of amyloid and apolipoprotein E (APOE) genotype on cognition among middle‐aged individuals.MethodsWe included 464 cognitively normal, test‐naïve, participants with Pittsburgh compound B positron emission tomography amyloid imaging, mean age of 62.7 (range, 51–71 years), enrolled in the Mayo Clinic Study of Aging. Participants completed multiple cognitive assessments, including a standard neuropsychological battery and the CogState computerized battery, over 30 months of follow‐up. Linear mixed models were used to examine the effects of amyloid and APOE genotype on baseline cognition and cognitive decline.ResultsElevated amyloid was not associated with tests of episodic memory but did predict declines on tests of executive function. APOE genotype was not associated with cognition. Among APOE ɛ4 noncarriers, higher amyloid was predictive of decline on tests of executive function and on one episodic memory test.DiscussionElevated amyloidosis and APOE genotype do not appear to exert a dramatic influence on cognition in middle age.

AbstractIntroductionThe feasibility and validity of brief computerized cognitive batteries at the population‐level are unknown.MethodsNondemented participants (n = 1660, age 50–97 years) in the Mayo Clinic Study on Aging completed the computerized CogState battery and standard neuropsychological battery. The correlation between tests was examined and comparisons between CogState performance on the personal computer (PC) and iPad (n = 331), and in the clinic vs. at home (n = 194), were assessed.ResultsWe obtained valid data on greater than 97% of participants on each test. Correlations between the CogState and neuropsychological tests ranged from −0.462 to 0.531. Although absolute differences between the PC and iPad were small and participants preferred the iPad, performance on the PC was faster. Participants performed faster on Detection, One Card Learning, and One Back at home compared with the clinic.DiscussionThe computerized CogState battery, especially the iPad, was feasible, acceptable, and valid in the population.