Lowe, Val J.

AbstractIntroductionWe investigated the association of the area deprivation index (ADI) with cognitive decline, mild cognitive impairment (MCI), and dementia in older adults (≥50 years old). ADI is a neighborhood socioeconomic disadvantage measure assessed at the census block group level.MethodsThe study included 4699 participants, initially without dementia, with available ADI values for 2015 and at least one study visit in 2008 through 2018. Using logistic regression and Cox proportional hazards models with age as the time scale, we assessed the odds for MCI and the risk for dementia, respectively.ResultsIn cognitively unimpaired (CU) adults at baseline, the risk for progression to dementia increased for every decile increase in the ADI state ranking (hazard ratio = 1.06, 95% confidence interval (1.01–1.11), P = .01). Higher ADI values were associated with subtly faster cognitive decline.DiscussionIn older CU adults, higher baseline neighborhood socioeconomic deprivation levels were associated with progression to dementia and slightly faster cognitive decline.Highlights The study used area deprivation index, a composite freely available neighborhood deprivation measure. Higher levels of neighborhood deprivation were associated with greater mild cognitive impairment odds. Higher neighborhood deprivation levels were associated with higher dementia risk.

Abstract PET imaging plays an essential role in achieving earlier and more specific diagnoses of dementia syndromes, important for clinical prognostication and optimal medical management. This has become especially vital with the recent development of pathology-specific disease-modifying therapy for Alzheimer disease, which will continue to evolve and require methods to select appropriate treatment candidates. Techniques that began as research tools such as amyloid and tau PET have now entered clinical use, making nuclear medicine physicians and radiologists essential members of the care team. This review discusses recent changes in the understanding of dementia and examines the roles of nuclear medicine imaging in clinical practice. Within this framework, multiple cases will be shown to illustrate a systematic approach of FDG PET interpretation and integration of PET imaging of specific molecular pathology including dopamine transporters, amyloid, and tau. The approach presented here incorporates contemporary understanding of both common and uncommon dementia syndromes, intended as an updated practical guide to assist with the sophisticated interpretation of nuclear medicine examinations in the context of this rapidly and continually developing area of imaging.

Background: Cerebral microbleeds (CMBs) are a common vascular pathology associated with future intracerebral hemorrhage. Plasma biomarkers of amyloid, tau, and neurodegeneration may provide a screening avenue to identify those with CMBs, but evidence is conflicting. Objective: To determine the association between plasma biomarkers (Aβ40, Aβ42, t-tau, p-tau181, p-tau217, neurofilament light chain (NfL)) and CMBs in a population-based study of aging and whether these biomarkers predict higher signal on Aβ-PET imaging in patients with multiple CMBs. Methods: 712 participants from the Mayo Clinic Study of Aging with T2* GRE MRI and plasma biomarkers were included. Biomarkers were analyzed utilizing Simoa (Aβ40, Aβ42, t-tau, NfL) or Meso Scale Discovery (p-tau181, p-tau217) platforms. Cross-sectional associations between CMBs, plasma biomarkers and Aβ-PET were evaluated using hurdle models and multivariable regression models. Results: Among the 188 (26%) individuals with≥1 CMB, a lower plasma Aβ42/Aβ40 ratio was associated with more CMBs after adjusting for covariables (IRR 568.5 95% CI 2.8–116,127). No other biomarkers were associated with risk or number CMBs. In 81 individuals with≥2 CMBs, higher plasma t-tau, p-tau181, and p-tau217 all were associated with higher Aβ-PET signal, with plasma p-tau217 having the strongest predictive value (r2 0.603, AIC –53.0). Conclusion: Lower plasma Aβ42/Aβ40 ratio and higher plasma p-tau217 were associated with brain amyloidosis in individuals with CMBs from the general population. Our results suggest that in individuals with multiple CMBs and/or lobar intracranial hemorrhage that a lower plasma Aβ42/Aβ40 ratio or elevated p-tau217 may indicate underlying cerebral amyloid angiopathy.

Introduction: Cerebrovascular disease (CVD) and neuropsychiatric symptoms (NPS) are common in older adults and are independently associated with cognitive impairment. In addition, vascular depression (a late-life depression) is hypothesized to be associated with cerebrovascular pathology. Hypothesis: CVD pathology imaging biomarkers (e.g., white matter hyperintensities (WMH), infarctions) are associated with depression and anxiety, and both (depression/anxiety and CVD imaging biomarkers) are independently associated with mild cognitive impairment (MCI). Methods: This cross-sectional study included 1739 Mayo Clinic Study of Aging participants (≥50 years old) without dementia, with comprehensive cognitive evaluations and available data on the Beck Depression Inventory II (BDI), the Beck Anxiety Inventory (BAI) and imaging CVD biomarkers via FLAIR-MRI (i.e., WMH% of total intracranial volume (TIV) and brain infarctions). We used linear and logistic regression models to examine the associations adjusting for age, sex, education, and apolipoprotein E ε4 status. Results: Participants’ mean age (SD) was 71.11 (10.61) years (53.3% males). Higher WMH% TIV burden was significantly associated with higher BDI (b= 0.082, 95%CI: 0.031, 0.133), p=0.002) and BAI scores (b= 0.088, 95%CI: 0.037, 0.140), p=0.001); the presence of infarctions was also associated with a higher BDI score. Both WMH %TIV burden (OR: 1.20 (95%CI:1.05, 1.38), p=0.008) and BDI score (OR: 1.38 (95%CI:1.21, 1.57), p<0.001) were significantly associated with MCI when included simultaneously in the model. We observed similar associations for CVD biomarkers and BAI score with MCI. Conclusions: CVD imaging biomarkers and NPS, as measured by BDI and BAI scores, could represent two distinct processes associated with cognitive impairment. Studies are ongoing to further examine these associations and delineate how CVD, NPS, and other pathophysiology processes (e.g., Alzheimer’s disease) interact and are associated with cognitive impairment.

AbstractBackgroundPosterior cortical atrophy (PCA) is one of the atypical Alzheimer's disease variants, characterized by predominant visuospatial and visuoperceptual deficits, with established dorsal and ventral subtypes. A third primary occipital (caudal) variant has been suggested. We aimed to determine its demographics, clinical manifestations, and biomarker findings.MethodsFifty‐two PCA patients were investigated. Patients underwent neuropsychological assessment, magnetic resonance imaging, and fluorodeoxyglucose (FDG)‐, amyloid‐, and tau‐positron emission tomography (tau‐PET) scans. Normalized regional FDG‐PET values were represented as z‐scores relative to a control population. Patients were divided into “primary occipital” and “other PCA” subgroups according to FDG‐PET‐defined criteria, with primary occipital defined as patients in which the z‐scores for occipital subregions were at least one standard deviation lower (SD) (i.e., more abnormal) than the z‐scores in all other brain regions. Global amyloid‐PET, temporo‐parietal FDG‐PET, and temporal tau‐PET regions‐of‐interest (ROIs) were calculated.ResultsNine patients were classified as primary occipital; they were older (p = 0.034) and had more years of education (p = 0.007) than other PCA patients. The primary occipital group performed worse on the Ishihara test for color perception (p < 0.001), while other PCA patients performed worse on the Western Aphasia Battery (WAB) praxis scale (p = 0.005). Overall neuropsychiatric symptom burden was lower in the primary occipital group (p < 0.001). The FDG‐PET meta‐ROI was higher in the primary occipital subtype (p = 0.006), but no differences were observed in amyloid‐ and tau‐PET.ConclusionsOur findings suggest that primary occipital PCA is characterized by an older age at onset, more color perception dysfunction, less severe ideomotor apraxia, and less hypometabolism in temporo‐parietal meta‐ROI compared to established phenotypes.

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.

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.