Faculty Bibliography

Poor cardiovascular health is strongly linked to increased risk of cognitive impairment and Alzheimer's disease and related dementias. This commentary discusses Yang and associates' work on the associations between cardiovascular health in middle age, as defined by Life Essential 8 scores, and later digital cognitive performance and incident Alzheimer's disease. We examine the strengths and weaknesses of their study within the broader research context. We emphasize the potential significance of sleep and stress the need for longitudinal studies incorporating robust neuropsychiatric methodologies, advanced neuroimaging techniques, and diverse participant samples to enhance the reliability and generalizability of results.

Obstructive sleep apnea (OSA) exerts pathogenic effects through a combination of sleep fragmentation (SF) and intermittent hypoxia (IH). The mechanisms through which sleep disruption impacts memory might arise by investigating disruption of specific sleep stages and, when such disruption occurs through OSA, by evaluating the individual contributions of SF and IH. Given region-specific EEG slow activity during non-REM sleep has been associated with overnight declarative, motor and spatial memory formation, we investigated the effects of disrupting slow wave sleep (SWS) on a virtual maze navigation task. Thirty three participants (24 male, 56 years old [range 28-68 years] with OSA (baseline AHI4%>20/hour) who were habitually well-treated and adherent to CPAP completed 3 timed trials on a 3D spatial maze before and after polysomnographically (PSG) recorded sleep. We restricted CPAP withdrawal to SWS through real-time monitoring of the PSG under three conditions: 1) stable-SWS on therapeutic CPAP, 2) SWS-CPAP withdrawal containing SF and IH, and 3) SWS-CPAP withdrawal with supplemental oxygen containing SF with reduced IH. SWS-specific CPAP withdrawal (with or without supplemental oxygen) did not significantly impact EEG slow oscillation or spatial navigational memory, despite effectively reducing %SWS and SWS bout length. Greater regional EEG slow oscillation (0.6-1Hz), but not delta (1-4Hz) activity, was associated with improvements in overnight memory during stable SWS in the CPAP condition. These observations suggest that slow oscillations may be important for overnight memory processing, and sleep disruptions of sufficient magnitude to reduce slow oscillations may be required to capture demonstrable change in spatial navigation performance.

Alzheimer's disease rates are expected to triple by 2050. Early detection and specific mitigation efforts are warranted to blunt the alarming increase. Physical function index (PFI) declines with age; additionally, higher PFI is associated with better cognitive functioning in middle-to-older age individuals. However, most studies utilize one domain of PFI to examine associations with cognition. Therefore, using clustering methods, the purpose of this investigation was to determine if high-risk individuals with higher PFI have better cognitive outcomes compared to individuals with lower PFI. Participants (n = 215; 73.1% female; 45-75 years) completed a body mass scan, venous blood draw, 7 PFI tasks, and 7 cognitive tests. A k-means cluster analysis was utilized to identify PFI cluster for participants, one-way ANCOVAs were used to assess differences in cognition among clusters. Cluster 1 (C1; n = 29) was characterized as the highest strength/power, faster dual-task walking time, and higher aerobic capacity, Cluster 3 (C3; n = 113) had the lowest values between PFI groups, Cluster 2 (C3; n = 74) was in-between C1 and C3. Individuals in C1 had significantly higher global cognitive, visuospatial scores, digital executive functioning and associative learning compared to individuals in C3 (p < 0.05). Individuals in C1 and C2 had significantly higher values on orientation task and figure recall than individuals in C3 (p < 0.05). The results from this current study demonstrate that individuals with higher combined PFI output have higher global cognitive scores than individuals with lower combined PFI output. Examining PFI variables together may be a valuable tool when assessing cognition among cognitively at-risk individuals.

Anxiety is highly prevalent in Alzheimer's disease (AD), correlating with cerebrospinal fluid/positron emission tomography biomarkers and disease progression. Relationships to plasma biomarkers are unclear. Herein, we compare levels of plasma biomarkers in research participants with and without anxiety at cognitively normal, mild cognitive impairment, and AD dementia stages. We observed significantly higher plasma tau/amyloid-β₄₂ ratio in AD participants with anxiety versus those without, but did not observe differences at other stages or plasma biomarkers. No such relationships were evident with depression. These results support a unique pathophysiological relationship between anxiety and AD that can be reflected in plasma biomarkers, suggestive of heightened neurodegeneration.

PURPOSE/OBJECTIVE:The pathological hallmarks of Alzheimer's disease (AD), amyloid, tau, and associated neurodegeneration, are present in the cortical gray matter (GM) years before symptom onset, and at significantly greater levels in carriers of the apolipoprotein E4 (APOE4) allele. Their respective biomarkers, A/T/N, have been found to correlate with aspects of brain biochemistry, measured with magnetic resonance spectroscopy (MRS), indicating a potential for MRS to augment the A/T/N framework for staging and prediction of AD. Unfortunately, the relationships between MRS and A/T/N biomarkers are unclear, largely due to a lack of studies examining them in the context of the spatial and temporal model of T/N progression. Advanced MRS acquisition and post-processing approaches have enabled us to address this knowledge gap and test the hypotheses, that glutamate-plus-glutamine (Glx) and N-acetyl-aspartate (NAA), metabolites reflecting synaptic and neuronal health, respectively, measured from regions on the Braak stage continuum, correlate with: (i) cerebrospinal fluid (CSF) p-tau181 level (T), and (ii) hippocampal volume or cortical thickness of parietal lobe GM (N). We hypothesized that these correlations will be moderated by Braak stage and APOE4 genotype. METHODS:We conducted a retrospective imaging study of 34 cognitively unimpaired elderly individuals who received APOE4 genotyping and lumbar puncture from pre-existing prospective studies at the NYU Grossman School of Medicine between October 2014 and January 2019. Subjects returned for their imaging exam between April 2018 and February 2020. Metabolites were measured from the left hippocampus (Braak II) using a single-voxel semi-adiabatic localization by adiabatic selective refocusing sequence; and from the bilateral posterior cingulate cortex (PCC; Braak IV), bilateral precuneus (Braak V), and bilateral precentral gyrus (Braak VI) using a multi-voxel echo-planar spectroscopic imaging sequence. Pearson and Spearman correlations were used to examine the relationships between absolute levels of choline, creatine, myo-inositol, Glx, and NAA and CSF p-tau181, and between these metabolites and hippocampal volume or parietal cortical thicknesses. Covariates included age, sex, years of education, Fazekas score, and months between CSF collection and MRI exam. RESULTS:There was a direct correlation between hippocampal Glx and CSF p-tau181 in APOE4 carriers (Pearson's r = 0.76, p = 0.02), but not after adjusting for covariates. In the entire cohort, there was a direct correlation between hippocampal NAA and hippocampal volume (Spearman's r = 0.55, p = 0.001), even after adjusting for age and Fazekas score (Spearman's r = 0.48, p = 0.006). This relationship was observed only in APOE4 carriers (Pearson's r = 0.66, p = 0.017), and was also retained after adjustment (Pearson's r = 0.76, p = 0.008; metabolite-by-carrier interaction p = 0.03). There were no findings in the PCC, nor in the negative control (late Braak stage) regions of the precuneus and precentral gyrus. CONCLUSIONS:Our findings are in line with the spatially- and temporally-resolved Braak staging model of pathological severity in which the hippocampus is affected earlier than the PCC. The correlations, between MRS markers of synaptic and neuronal health and, respectively, T and N pathology, were found exclusively within APOE4 carriers, suggesting a connection with AD pathological change, rather than with normal aging. We therefore conclude that MRS has the potential to augment early A/T/N staging, with the hippocampus serving as a more sensitive MRS target compared to the PCC.

BACKGROUND:Although related, the precise mechanisms linking obstructive sleep apnea (OSA) and cardiovascular disease (CVD) are unclear. Platelets are mediators of CVD risk and thrombosis and prior studies suggested associations of OSA and platelet activity. The aim of this study is to assess the link between OSA, platelet activity, and CVD-related risk factors. METHODS AND RESULTS/RESULTS:=0.002). No associations were detected in nonaspirin users (n=417). CONCLUSIONS:No associations were detected between OSA and platelet aggregation in a community sample. Our finding that OSA associates with increased platelet aggregation in the aspirin group, most of whom use it for primary prevention of CVD, suggests that platelet aggregation may mediate the adverse impact of OSA on vascular health in individuals with existing CVD risk, supporting further investigation.

OBJECTIVE/UNASSIGNED:The purpose of this study was to determine whether social support from extended family and church members moderate the association between chronic stress exposure and sleep quality in a nationally representative sample of African American adults. DESIGN/UNASSIGNED:Data from African American respondents aged 18 and older were drawn from the National Survey of American Life-Reinterview. The analytic sample for this study included 1,372 African American adults who attended religious services at least a few times a year, as the church-based relationship measures were only assessed for these individuals. Self-reported sleep quality was assessed by sleep satisfaction, trouble falling asleep, and restless sleep. Chronic stress exposure was measured by a nine-item index. OLS and logistic regression were used to estimate the relationship between chronic stress exposure, extended family and church relationships, and sleep quality. RESULTS/UNASSIGNED:The data indicated that chronic stress exposure was associated with decreased sleep satisfaction, increased likelihood of trouble falling asleep and restless sleep. Receiving emotional support from family and more frequent contact with church members were associated with decreased restless sleep. Emotional family support moderated the associations between chronic stress exposure and trouble falling asleep and restless sleep. The positive associations between chronic stress exposure and these two sleep quality measures were attenuated among respondents who received high levels of emotional support from their family. CONCLUSIONS/UNASSIGNED:Together, these findings underscore the detriment of chronic stress exposure to African Americans' sleep quality and suggest that extended family members are effective stress coping resources and play an important role in this population's sleep quality.