Citations

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 Introduction We have previously shown that older adults with excessive daytime sleepiness (EDS) appear to be more vulnerable to longitudinal amyloid PET accumulation before the onset of the dementia. It remains unclear whether this vulnerability is specific to amyloid or extends to other biomarkers of Alzheimer’s disease pathology, or axonal integrity and inflammation, which can also contribute to neurodegeneration and cognitive changes. Methods For this cross-sectional analysis, we identified 260 cognitively unimpaired adults (>60 years old) without neurologic disorder who underwent CSF quantification of AD biomarkers (CSF Aβ-42, p-tau181, p-tau217) along with at least one other biomarker of interest (neurofilament light chain [NfL], IL-6, IL-10, and TNF-α) from the Mayo Clinic Study of Aging – a longitudinal population-based cohort in Olmsted County, Minnesota. CSF biomarkers were available in 251-260 individuals, depending on the biomarker. We fit linear regression models to assess whether the CSF biomarkers were associated with sleepiness as measured by the Epworth Sleepiness Scale (ESS), after controlling for age, sex, APOE4 genotype, BMI, hypertension, dyslipidemia, and OSA diagnosis (by chart review). Results Higher ESS scores were independently associated with higher CSF IL-6 and NfL, but not with the other biomarkers in the whole sample. For every single-point increase in the ESS score, there was a .008 ([95% CI .001-.016], p=0.033) increase in the log of IL-6 and .01 ([95% CI .002-.018], p=0.016) increase in the log of NfL. A sensitivity analysis showed a correlation between ESS scores and log of p-tau/Aβ-42 ratio only in participants with abnormal ratio (>0.023), after controlling for APOE4 (partial r=.27, p=039). Conclusion Our results corroborate previous literature suggesting that higher inflammatory milieu reflected by increased CSF IL-6 is associated with sleepiness. The association between NfL and sleepiness suggests that sleepiness may be related to disturbed connectivity due to axonal damage. Alternatively, NfL may be a surrogate of active axonal injury associated with more disrupted sleep. A correlation between sleepiness and CSF p-tau/ab-42 ratio was only seen in patients with abnormal ratio, suggesting a stronger association between sleepiness and AD pathology as the disease progresses, possibly because AD pathology worsens sleep quality and/or vice-versa. Support (If Any) NIH/NIA

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: 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.

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.

Background: Alzheimer’s disease can present atypically as a progressive dysexecutive syndrome (dAD), an entity that preferentially affects younger individuals and is frequently misdiagnosed, highlighting the imperative for additional research. Objective: The objective of this study is to characterize the clinical, antemortem neuroimaging, and postmortem neuropathologic features of two cases of young-onset dAD who displayed evidence of Lewy body disease (LBD) co-pathology at autopsy. Methods: Clinical histories, antemortem MRI and PET imaging, and postmortem neuropathologic data were reviewed for each patient. Case Descriptions/Results: Canonical features of dAD were observed in both cases, including progressive and predominant impairment in tasks related to working memory and cognitive flexibility, a lack of major behavioral/personality changes, and evidence of abnormal amyloid and tau deposition by antemortem amyloid and tau PET and postmortem neuropathology. Relative sparing of hippocampal involvement was observed in both individuals, in keeping with many cases of clinically atypical AD. One of the patients developed subtle parkinsonian signs as well as paranoia and irritability in the years prior to passing. In both cases, transitional (brainstem and limbic) LBD co-pathology was observed at autopsy. Discussion: Although LBD co-pathology is not uncommon in AD overall, the presence of LBD pathology in these young-onset cases of dAD (including a case with apparent symptomatic correlate) warrants further investigation for broader frequency and underlying pathophysiology. Conclusion: A better understanding of which specific young-onset AD phenotypes are associated with LBD co-pathology would have important implications for counseling, treatment, clinical trial enrollment, and knowledge on disease mechanisms.