Przybelski, Scott A.

Objective To investigate the associations between age, vascular health, and Alzheimer disease (AD) imaging biomarkers in an elderly sample. Methods We identified 430 individuals along the cognitive continuum aged >60 years with amyloid positron emission tomography (PET), tau PET, and magnetic resonance imaging (MRI) scans from the population‐based Mayo Clinic Study of Aging. A subset of 329 individuals had fluorodeoxyglucose (FDG) PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from health care records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health. We used global amyloid from Pittsburgh compound B PET, entorhinal cortex tau uptake (ERC‐tau) from tau‐PET, and neurodegeneration in AD signature regions from MRI and FDG‐PET as surrogates for AD pathophysiology. We dichotomized participants into CMC = 0 (CMC − ) versus CMC > 0 (CMC + ) and tested for age‐adjusted group differences in AD biomarkers. Using structural equation models (SEMs), we assessed the impact of vascular health on AD biomarker cascade (amyloid leads to tau leads to neurodegeneration) after considering the direct and indirect age, sex, and apolipoprotein E effects. Results CMC + participants had significantly greater neurodegeneration than CMC − participants but did not differ by amyloid or ERC‐tau. The SEMs showed that (1) vascular health had a significant direct and indirect impact on neurodegeneration but not on amyloid; and (2) vascular health, specifically the presence of hyperlipidemia, had a significant direct impact on ERC‐tau. Interpretation Vascular health had quantifiably greater impact on neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies are warranted to clarify the relationship between tau deposition and vascular health. Ann Neurol 2017;82:706–718

Altered cortical thickness has been observed in aging and various neurodegenerative disorders. Furthermore, reduced hippocampal volume has been reported in late-life depression. Even mild depressive symptoms are common in the elderly. However, little is known about the structural MRI measures of depressive symptoms in normal cognitive aging. Thus we sought to examine the association between depressive symptoms with cortical thickness and hippocampal volume as measured by brain MRI among community-dwelling participants. We conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging, involving cognitively normal participants ( N = 1,507) aged≥70 years. We observed that depressive symptoms were associated with lower global cortical thickness and lower thickness in specific prefrontal and temporal cortical regions, labeled by FreeSurfer software, version 5.3. As expected, the strength of correlation was very small, given that participants were community-dwelling with only mild depressive symptoms. We did not observe associations between hippocampal volume and depressive symptoms. These findings may provide insight into the structural correlates of mild depressive symptoms in elderly participants.

Background: There is growing interest in white matter (WM) imaging with positron emission tomography (PET). Objectives: We studied the association of cognitive function in late multiple sclerosis (MS) with cortical and WM Pittsburgh compound-B PET (PiB-PET) binding. Methods: In the population-based Mayo Clinic Study of Aging, 24 of 4869 participants had MS (12 underwent PiB-PET). Controls were age and sex matched (5:1). We used automated or semi-automated processing for quantitative image analyses and conditional logistic regression for group differences. Results: MS patients had lower memory ( p = 0.03) and language ( p = 0.02) performance; smaller thalamic volumes ( p = 0.003); and thinner temporal ( p = 0.001) and frontal ( p = 0.045) cortices on magnetic resonance imaging (MRI) than controls. There was no difference in global cortical PiB standardized uptake value ratios between MS and controls ( p = 0.35). PiB uptake was lower in areas of WM hyperintensities compared to normal-appearing white matter (NAWM) in MS ( p = 0.0002). Reduced PiB uptake in both the areas of WM hyperintensities ( r = 0.65; p = 0.02) and NAWM ( r = 0.69; p = 0.01) was associated with decreased visuospatial performance in MS. Conclusion: PiB uptake in the cortex in late MS is not different from normal age-matched controls. PiB uptake in the WM in late MS may be a marker of the large network structures’ integrity such as those involved in visuospatial performance.

AbstractIntroductionTau‐positron emission tomography (PET) imaging with AV1451 is sensitive to Alzheimer disease (AD)–related tau deposition in the brain. We (1) examined regional variation of average tau‐PET standardized uptake value ratios (SUVRs) in a young normal population (30–49 years) and corrected for the regional variability and (2) tested if the standardized values (z‐scores) scaled appropriately to capture regional Alzheimer‐specific (i.e., amyloid sensitive) tau‐PET changes in individuals aged 50+ years.MethodsWe identified 490 individuals (70 between 30–49 years as a reference group and 420 cognitively normal between 50–95 years of age) with tau‐PET and amyloid PET scans from the Mayo Clinic Study of Aging.ResultsThere was intrinsic regional variability in average tau‐PET SUVR with uptakes higher in some regions than others, even in the younger individuals who would have minimal or no neurofibrillary tangles. We corrected for this using region of interest–specific z‐scores based on the reference group. Amyloid and tau‐PET uptake were associated throughout the brain after adjusting for age, with the highest correlations in the medial temporal regions.DiscussionRegions with high‐average SUVR are not necessarily those with the greatest tau pathology. Standardization is therefore recommended. Standardization of the data “realigns” the data such that the regional tau z‐scores are informative of the disease process, that is, regions with high z‐scores now coincide with regions correlated with amyloid deposition. Medial temporal structures, specifically entorhinal cortex–tau, may be useful as an AD‐specific tau‐PET signature due to its sensitivity to amyloid.