Petersen, Ronald C.

Introduction: Coronary artery disease (CAD) has been associated with cognitive decline. Cardiac rehabilitation (CR) is a class 1A recommendation for patients with CAD as it reduces future cardiac events and mortality. However, the impact of CR on incidence of mild cognitive impairment (MCI) and dementia has not been extensively studied. We investigated the association of CAD on incidence of MCI and dementia; and whether CR attendance reduces incidence of MCI and dementia in patients with CAD Methods: The Mayo Clinic Study of Aging (MCSA), a prospective, population-based cohort was probed for this study. At baseline and every 15-months thereafter, subjects were evaluated for MCI and dementia using a standardized protocol. Data on CR participation were collected via record linkage to the Rochester Epidemiology Project. To evaluate association with incident MCI or dementia, cox proportional hazard models were used and adjusted for age, sex, and clinical predictors of cognitive decline. Participants with MCI at baseline were excluded for MCI analysis and adjusted for in dementia analysis. Results: We included 5960 MCSA participants (female: 50%; age: 70±13). Of those, 1934 participants (32%) had CAD and 702 (12%) had MCI at baseline. Mean follow-up was 3.9±3.7yrs, with 760 incident cases of MCI (13%) and 290 cases of dementia (5%). CAD was a significant predictor of MCI and dementia, although after adjustment for other clinical predictors, CAD was only associated with MCI incidence ( Table 1, Figure ). Incidence of dementia was reduced in CAD patients who had a greater attendance at CR when adjusted for other predictors of cognitive decline ( Table 2 ). Attendance at CR did not reduce incidence of MCI ( Table 2 ). Conclusions: CAD was a significant predictor of MCI and dementia. In patients with CAD, a higher attendance of CR was associated with reduced incidence of dementia but not MCI. Specific CR programming and outcome targets may be needed to prevent MCI in patients with CAD.

AbstractBackgroundHospitalization in older age is associated with accelerated cognitive decline, typically preceded by neuropathologic changes. We assess the association between indication for hospitalization and brain neurodegeneration.MethodsIncluded were participants from the Mayo Clinic Study of Aging, a population-based longitudinal study, with ≥1 brain imaging available in those older than 60 years of age between 2004 and 2017. Primary analyses used linear mixed-effects models to assess association of hospitalization with changes in longitudinal trajectory of cortical thinning, amyloid accumulation, and white matter hyperintensities (WMH). Additional analyses were performed with imaging outcomes dichotomized (normal vs abnormal) using Cox proportional hazards regression.ResultsOf 2 480 participants, 1 966 had no hospitalization and 514 had ≥1 admission. Hospitalization was associated with accelerated cortical thinning (annual slope change −0.003 mm [95% confidence interval (CI) −0.005 to −0.001], p = .002), but not amyloid accumulation (0.003 [95% CI −0.001 to 0.006], p = .107), or WMH increase (0.011 cm3 [95% CI −0.001 to 0.023], p = .062). Interaction analyses assessing whether trajectory changes are dependent on admission type (medical vs surgical) found interactions for all outcomes. While surgical hospitalizations were not, medical hospitalizations were associated with accelerated cortical thinning (−0.004 mm [95% CI −0.008 to −0.001, p = .014); amyloid accumulation (0.010, [95% CI 0.002 to 0.017, p = .011), and WMH increase (0.035 cm3 [95% CI 0.012 to 0.058, p = .006). Hospitalization was not associated with developing abnormal cortical thinning (p = .407), amyloid accumulation (p = .596), or WMH/infarctions score (p = .565).ConclusionsMedical hospitalizations were associated with accelerated cortical thinning, amyloid accumulation, and WMH increases. These changes were modest and did not translate to increased risk for crossing the abnormality threshold.

ABSTRACT Background and Objective Patients with dementia with Lewy bodies (DLB) may have overlapping Alzheimer's disease pathology. We investigated the longitudinal rate of tau accumulation and its association with neurodegeneration and clinical disease progression in DLB. Methods Consecutive patients with probable DLB (n = 22) from the Mayo Clinic Alzheimer's Disease Research Center and age‐matched and sex‐matched cognitively unimpaired controls (CU; n = 22) with serial magnetic resonance imaging and flortaucipir positron emission tomography scans within an average of 1.6 years were included. Regional annualized rates of flortaucipir uptake standardized uptake value ratios (SUVr) were calculated. Regional annualized rates of cortical volume change were measured with the Tensor Based Morphometry–Syn algorithm. Results The annual increase of flortaucipir SUVr was greater in the middle and superior occipital, fusiform, and inferior parietal cortices in DLB (mean: 0.017, 0.019, 0.019, and 0.015, respectively) compared with the CU (mean: −0.006, −0.009, −0.003, and − 0.005, respectively; P < 0.05). In patients with DLB (but not the CU), a longitudinal increase in flortaucipir SUVr was associated with longitudinal cortical atrophy rates in the lateral occipital and inferior temporoparietal cortices, hippocampus, and the temporal pole as well as a concurrent decline on Mini‐Mental State Examination and Clinical Dementia Rating–Sum of Boxes in the lateral occipital and the fusiform cortices. Conclusions Tau accumulation was faster in DLB compared with the CU, with increased accumulation rates in the lateral occipital and temporoparietal cortices. These increased rates of tau accumulation were associated with neurodegeneration and faster disease progression in DLB. Tau may be a potential treatment target in a subset of patients with DLB. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Abstract Introduction : Plasma glial fibrillary acidic protein (GFAP) may be associated with amyloid burden, neurodegeneration, and stroke but its specificity for Alzheimer's disease (AD) in the general population is unclear. We examined associations of plasma GFAP with amyloid and tau positron emission tomography (PET), cortical thickness, white matter hyperintensities (WMH), and cerebral microbleeds (CMBs). Methods : The study included 200 individuals from the Mayo Clinic Study of Aging who underwent amyloid and tau PET and magnetic resonance imaging and had plasma GFAP concurrently assayed; multiple linear regression and hurdle model analyses were used to investigate associations controlling for age and sex. Results : GFAP was associated with amyloid and tau PET in multivariable models. After adjusting for amyloid, the association with tau PET was no longer significant. GFAP was associated with cortical thickness, WMH, and lobar CMBs only among those who were amyloid‐positive. Discussion : This cross‐sectional analysis demonstrates the utility of GFAP as a plasma biomarker for AD‐related pathologies.

AbstractIntroductionAn analysis of the ethnocultural and socioeconomic composition of Alzheimer's Disease Neuroimaging Initiative (ADNI) participants is needed to assess the generalizability of ADNI data to diverse populations.MethodsADNI data collected between October 2004 and November 2020 were used to determine ethnocultural and educational composition of the sample and differences in the following metrics: screening, screen fails, enrollment, biomarkers.ResultsOf 3739 screened individuals, 11% identified as being from ethnoculturally underrepresented populations (e.g., Black, Latinx) and 16% had <12 years of education. Of 2286 enrolled participants, 11% identified as ethnoculturally underrepresented individuals and 15% had <12 years of education. This participation is considerably lower than US Census data for adults 60+ (ethnoculturally underrepresented populations: 25%; <12 years of education: 4%). Individuals with <12 years of education failed screening at a higher rate.DiscussionOur findings suggest that ADNI results may not be entirely generalizable to ethnoculturally diverse and low education populations.

Abstract Introduction We examined the association between cerebrospinal fluid (CSF)‐derived biomarkers of Alzheimer's disease and neuropsychiatric symptoms (NPS) in older non‐demented adults. Methods We included 784 persons (699 cognitively unimpaired, 85 with mild cognitive impairment) aged ≥ 50 years who underwent CSF amyloid beta (Aβ42), hyperphosphorylated tau 181 (p‐tau), and total tau (t‐tau) as well as NPS assessment using Beck Depression and Anxiety Inventories (BDI‐II, BAI), and Neuropsychiatric Inventory Questionnaire (NPI‐Q). Results Lower CSF Aβ42, and higher t‐tau/Aβ42 and p‐tau/Aβ42 ratios were associated with BDI‐II and BAI total scores, clinical depression (BDI‐II ≥ 13), and clinical anxiety (BAI ≥ 10), as well as NPI‐Q–assessed anxiety, apathy, and nighttime behavior. Discussion CSF Aβ42, t‐tau/Aβ42, and p‐tau/Aβ42 ratios were associated with NPS in community‐dwelling individuals free of dementia. If confirmed by a longitudinal cohort study, the findings have clinical relevance of taking into account the NPS status of individuals with abnormal CSF biomarkers.