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Post-stroke cognitive impairment (PSCI) occurs in 20-40% of patients 3-6 months after stroke. However, the question regarding risks of recurrent stroke and death in patients with PSCI remains controversial. The goal of this study was to conduct meta-analysis of published literature to estimate the risks of stroke recurrence and death associated with PSCI, as well as to assess the quality of these studies, and to identify sources of variation. Electronic databases (PubMed, EMbase, Google Scholar, Cochrane Library, and Scopus) were screened for eligible studies published from 1992 to 2019. Study quality was assessed using the Newcastle Ottawa Scale. Risk of bias in non-randomized and randomized studies was assessed using ROBINS-E and RoB 2 tools, respectively. Funnel plots and selection models were used for evaluating publication bias. Heterogeneity was assessed using a combination of statistics: I 2 , Q -statistic, and Kendall τ 2 . Estimates were obtained using a random effects model and restricted maximum likelihood estimation. Pooled estimates for the two outcomes of interest were calculated as hazard ratios (HR) with 95% confidence intervals (CIs). We included eight studies examining the effect of PSCI on risk of stroke recurrence. We found no evidence of potential publication bias among the included studies in stroke recurrence (χ 2 =3.440, p=0.487) and mortality (χ 2 =3.797, p=0.150). Pooled data from the eight studies involving n=1,840 PSCI and n=5,824 non-PSCI showed that the hazard of recurrent stroke risk was significantly higher in individuals with PSCI compared to non-PSCI participants (HR = 1.71; 95% CI: 1.45 - 2.01; I 2 = 0%). Seventeen studies were included examining the impact of PSCI on mortality risk. The pooled data from these studies comprised n=7,591 PSCI and n=22,328 non-PSCI study participants. The pooled hazard of mortality was significantly higher in the PSCI group relative to the non-PSCI group (HR = 1.98; 95% CI: 1.64 - 2.40; I 2 = 82.95%). This meta-analysis shows an increased risk of mortality and recurrent stroke in patients with PSCI. Post-stroke cognitive testing may identify patients at a higher risk of stroke recurrence and death who may require more aggressive interventions for secondary prevention.

More than 50 million older people worldwide are suffering from dementia, and this number is estimated to increase to 150 million by 2050. Greater caregiver burdens and financial impacts on the healthcare system are expected as we wait for an effective treatment for dementia. Researchers are constantly exploring new therapies and screening approaches for the early detection of dementia. Artificial intelligence (AI) is widely applied in dementia research, including machine learning and deep learning methods for dementia diagnosis and progression detection. Computerized apps are also convenient tools for patients and caregivers to monitor cognitive function changes. Furthermore, social robots can potentially provide daily life support or guidance for the elderly who live alone. This review aims to provide an overview of AI applications in dementia research. We divided the applications into three categories according to different stages of cognitive impairment: (1) cognitive screening and training, (2) diagnosis and prognosis for dementia, and (3) dementia care and interventions. There are numerous studies on AI applications for dementia research. However, one challenge that remains is comparing the effectiveness of different AI methods in real clinical settings.

Nearly 350,000 lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) adults in the U.S. are currently living with Alzheimer’s disease and related dementias (ADRD). Informal caregivers face challenges impacting their ability to access and receive adequate and inclusive care for LGBTQ+ persons living with ADRD. The purpose of this study was to determine the feasibility and acceptability of the Savvy Caregiver Program for caregivers of LGBTQ+ individuals living with ADRD. Data for this secondary analysis come from caregivers (n = 17) who completed 6 sessions of the Savvy program. Caregivers were very satisfied with tailored program activities. Analyses of trends suggest non-significant increases in positive aspects of caregiving and decreases in caregiver burden and depressive symptoms. This is the first known study assessing the feasibility of the Savvy Caregiver Program for caregivers of LGBTQ+ individuals living with ADRD. Future research on the Savvy Caregiver Program for caregivers of LGBTQ+ people living with ADRD is needed.

OBJECTIVES: To examine associations of pituitary-ovarian hormone levels with cognition before and after different formulations of hormone therapy (HT) or placebo independent of treatment group. METHODS: Recently menopausal, healthy women were randomized to 0.45 mg/day oral conjugated equine estrogens (o-CEE, n = 109), 50 μg/day transdermal 17β (tE2, n = 107) or placebo pills and patches (n = 146); women on active treatment received oral 200 mg/day micronized progesterone for 12 days per month. Levels of estrone, 17β-estradiol, follicle stimulating hormone, luteinizing hormone, androstenedione, and testosterone were determined prior to and after 48 months of study participation. Neuropsychological testing was administered at baseline, and months 18, 36 and 48. Latent growth curve models controlling for education level, age, APOE allele status, waist circumference, and treatment examined the trajectories of each cognitive domain after accounting for the effect of hormone levels at baseline and months 18, 36 and 48. A linear multivariate mixed model examined the effect of changes in hormone levels on changes in trajectories of complex attention tasks with varying degrees of difficulty. RESULTS: All women were adherent to treatment at month 48. Higher baseline estrone levels were associated with poorer global cognition, auditory attention and working memory, visual attention, and executive function, but not working memory. Higher levels of baseline 17β-E2 were associated with poorer cognitive performance, with marginal significance at baseline in speeded language and mental flexibility (p = 0.013). Other hormone levels were not associated with cognition. Controlling for all treatments, hormone levels at baseline and at month 48 did not have any significant correlation with cognitive trajectories over time. SUMMARY: In healthy, recently menopausal women, baseline estrone levels were inversely associated with selected cognitive factors independent of two types of HT or placebo during 4 years of follow-up. Baseline levels of the other pituitary-ovarian hormones studied were not associated with baseline cognition, nor were changes in any hormones associated with changes in cognition during the study. The marginal association between estradiol levels and cognitive factors warrants further investigation.

Left ventricular (LV) electrical maladaptation to increased heart rate in failing myocardium contributes to morbidity and mortality. Recently, cardiac cholinergic neuron activation reduced loss of contractile function resulting from chronic transverse-ascending aortic constriction (TAC) in rats. We hypothesized that chronic activation of cardiac cholinergic neurons would also reduce TAC-induced derangement of cardiac electrical activity. We investigated electrophysiological rate adaptation in TAC rat hearts with and without daily chemogenetic activation of hypothalamic oxytocin neurons for downstream cardiac cholinergic neuron stimulation. Sprague–Dawley rat hearts were excised, perfused, and optically mapped under dynamic pacing after 16 wk of TAC with or without 12 wk of daily chemogenetic treatment. Action potential duration at 60% repolarization (APD60) and conduction velocity (CV) maps were analyzed for regional rate adaptation to dynamic pacing. At lower pacing rates, untreated TAC induced elevated LV epicardial APD60. Fitted APD60 steady state (APDss) was reduced in treated TAC hearts. At higher pacing rates, treatment heterogeneously reduced APD60, compared with untreated TAC hearts. Variance of conduction loss was reduced in treated hearts compared with untreated hearts during fast pacing. However, CV was markedly reduced in both treated and untreated TAC hearts throughout dynamic pacing. At 150 ms pacing cycle length, APD60 versus diastolic interval dispersion was reduced in treated hearts compared with untreated hearts. Chronic activation of cardiac cholinergic neurons improved electrophysiological adaptation to increases in pacing rate during the development of TAC-induced heart failure. This provides insight into the electrophysiological benefits of cholinergic stimulation as a treatment for patients with heart failure. NEW & NOTEWORTHY Analysis of electrophysiology from optical mapping of failing left ventricular myocardium provided insight into the possible therapeutic outcomes of cholinergic stimulation within the left ventricle. Chronic hypothalamic oxytocin neuron activation for downstream cardiac cholinergic neuron stimulation blunted onset of failing electrophysiology induced by pressure overload-induced heart failure in rats.

Post-stroke cognitive impairment (PSCI) occurs in 20%-40% of stroke patients and was reported to be a risk factor of recurrent stroke and death. However, to date, no systematic review and meta-analysis exists to precisely estimate the associated risk. The goal of the current study was to conduct a systematic review of published literature on the association between PSCI and risk of recurrent stroke and death. We searched Ovid MEDLINE and Scopus for studies published from 1992 to 2019, combining the following keywords: post-stroke cognitive impairment, risk of stroke recurrence, mortality, post-stroke dementia. Of the 929 references, we identified 23 studies (n=28,305 patients) that met eligibility criteria. The time of PSCI diagnosis ranged from 7 days to 6 months, and 3-month after stroke was the most common time point of neuropsychological testing. The majority (65%, 15/23) of these studies evaluated PSCI mortality endpoint (n = 23,554), while 35% (8/23) looked at combined endpoint of recurrent stroke and death (n= 4,751). In mortality studies, 86% (13/15) showed significantly higher risk of death in PSCI patients compared to those without it (OR/HR/RR range from 1.42 to 7.42). In the two largest studies (n=8,822 and n=6,504), the adjusted HR were 1.42 (1.34-1.50) and RR 2.0 (1.3-3.2) respectively. Only 14% (2/15) of the studies showed negative results. However, one negative study [HR: 1.00 (0.79-1.86)] included a large cohort (n=3,948). In recurrence studies, 75% (6/8) reported higher risk with OR/HR/RR ranging from 1.48 to 4.86. Subgroup analyses in the two largest recurrence clinical trial studies (n=1,528 and n=1,240) reported HR 1.48 (1.04-2.09) and OR 2.32 (1.10-4.89). No association between PSCI and recurrent stroke was found in 25% (2/8) of recurrence studies including those with n=458 [HR 1.74 (0.89-3.39)] and n=202 patients [RR 1.25 (0.47-3.33)].This systematic review revealed about a 0.5 to 7 times increased risk of recurrent stroke and death in patients with PSCI suggesting that PSCI might be a marker predicting recurrent events in secondary stroke prevention. A meta-analysis is warranted to increase the precision and validity of risk estimates of PSCI and study the bases for differences across studies.

Background Activation of the oxytocin network has shown benefits in animal models of Obstructive Sleep Apnea (OSA) as well as other cardiorespiratory diseases. We sought to determine if nocturnal intranasal oxytocin administration could have beneficial effects in reducing the duration and/or frequency of obstructive events in obstructive sleep apnea subjects. Methods Two sequential standard “in-lab” polysomnogram (PSG) sleep studies were performed in patients diagnosed with OSA that were randomly assigned to initially receive either placebo or oxytocin (40 i.u.) administered intranasally in this double blinded randomized placebo controlled study. Changes in cardiorespiratory events during sleep, including apnea and hypopnea durations and frequency, risk of event-associated bradycardias, arterial oxygen desaturation and respiratory rate were assessed in 2 h epochs following sleep onset. Oxytocin significantly decreased the duration of obstructive events, as well as the oxygen desaturations and incidence of bradycardia that were associated with these events. Notably, oxytocin increased respiratory rate during non-obstructive periods. There were no significant changes in sleep architecture and no adverse effects were reported. Conclusions Oxytocin administration can benefit OSA subjects by reducing the duration and adverse consequences of obstructive events. Oxytocin could also be beneficial in situations involving respiratory depression as oxytocin increased respiratory rate. Additional studies are needed to further understand the mechanisms by which oxytocin promotes these changes in cardiorespiratory function. The long-term efficacy and optimal dose of intranasal oxytocin treatment should also be determined in OSA subjects. ClinicalTrials.gov NCT03148899.

Background/Purpose The patient-centered medical home (PCMH) is an enhanced model of primary care. This study examined to what extent nurse practitioner (NP)-led PCMHs differed from traditional physician-led PCMHs. Methods We tested for differences between 391 NP-led PCMHs and 11,479 physician-led PCMHs, as well as across two distinct clusters identified by the Two-Step cluster analysis procedure using a sample of 136 practices. Findings NP‐led PCMHs were more likely to serve vulnerable populations in rural and underserved areas than physician-led PCMHs. NP-led PCMHs tended to be more responsive to population health needs in the areas during the recognition process, while physician-led PCMHs emphasized practice improvements through enhanced access to care and management of patient information data. Discussion The findings suggest possible differences in capabilities, priorities and needs of the population served across practices. This is an important guide as policymakers track the adoption of PCMHs.

Examining the emotional functioning of individuals with mild cognitive impairment (MCI) could help describe their cognitive status and inform the development of interventions. This study compared the emotional characteristics of socially isolated older adults with and without MCI.We used baseline data from the Internet-based Conversational Engagement Clinical Trial. Emotional characteristics were assessed with the National Institutes of Health Toolbox Emotion Battery (NIHTB-EB). MCI status was determined with a consensus clinical diagnosis.This study included 163 participants (mean age = 81.2 years, non-Hispanic Black = 20.7%, MCI = 52.8%). MCI was associated with higher negative affect and lower psychological well-being. Non-Hispanic Black participants scored lower in sadness, higher in positive affect, and higher in meaning and purpose than non-Hispanic White participants.Older adults with MCI experience more negative emotions and worse psychological well-being than those with normal cognition. The NIHTB-EB appears to be a sensitive tool to detect emotional characteristics associated with cognitive decline.

Objective:This study compared the level of education and tests from multiple cognitive domains as proxies for cognitive reserve.Method:The participants were educationally, ethnically, and cognitively diverse older adults enrolled in a longitudinal aging study. We examined independent and interactive effects of education, baseline cognitive scores, and MRI measures of cortical gray matter change on longitudinal cognitive change.Results:Baseline episodic memory was related to cognitive decline independent of brain and demographic variables and moderated (weakened) the impact of gray matter change. Education moderated (strengthened) the gray matter change effect. Non-memory cognitive measures did not incrementally explain cognitive decline or moderate gray matter change effects.Conclusions:Episodic memory showed strong construct validity as a measure of cognitive reserve. Education effects on cognitive decline were dependent upon the rate of atrophy, indicating education effectively measures cognitive reserve only when atrophy rate is low. Results indicate that episodic memory has clinical utility as a predictor of future cognitive decline and better represents the neural basis of cognitive reserve than other cognitive abilities or static proxies like education.

OBJECTIVE:The Kronos Early Estrogen Prevention Study (KEEPS) was designed to address gaps in understanding the effects of timely menopausal hormone treatments (HT) on cardiovascular health and other effects of menopause after the premature termination of the Women's Health Initiative. METHOD:The KEEPS was a randomized, double-blinded, placebo-controlled trial to test the hypothesis that initiation of HT (oral conjugated equine estrogens [o-CEE] or transdermal 17β-estradiol [t-E2]) in healthy, recently postmenopausal women (n = 727) would slow the progression of atherosclerosis as measured by changes in carotid artery intima-media thickness (CIMT). RESULTS:After 4 years, neither HT affected the rate of increase in CIMT. There was a trend for reduced accumulation of coronary artery calcium with o-CEE. There were no severe adverse effects, including venous thrombosis. Several ancillary studies demonstrated a positive effect on mood with o-CEE, and reduced hot flashes, improved sleep, and maintenance of bone mineral density with both treatments. Sexual function improved with t-E2. There were no significant effects of either treatment on cognition, breast pain, or skin wrinkling. Variants of genes associated with estrogen metabolism influenced the age of menopause and variability in effects of the HT on CIMT. Platelet activation associated with the development of white matter hyperintensities in the brain. CONCLUSIONS:KEEPS and its ancillary studies have supported the value and safety of the use of HT in recently postmenopausal women and provide a perspective for future research to optimize HT and health of postmenopausal women. The KEEPS continuation study continues to pursue these issues.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.

Hormone therapy improves sleep in menopausal women and recent data suggest that transdermal 17β-estradiol may reduce the accumulation of cortical amyloid-β. However, how menopausal hormone therapies modify the associations of amyloid-β accumulation with sleep quality is not known. In this study, associations of sleep quality with cortical amyloid-β deposition and cognitive function were assessed in a subset of women who had participated in the Kronos early estrogen prevention study. It was a randomized, placebo-controlled trial in which recently menopausal women (age, 42-58; 5-36 months past menopause) were randomized to (1) oral conjugated equine estrogen (n = 19); (2) transdermal 17β-estradiol (tE2, n = 21); (3) placebo pills and patch (n = 32) for 4 years. Global sleep quality score was calculated using Pittsburgh sleep quality index, cortical amyloid-β deposition was measured with Pittsburgh compound-B positron emission tomography standard uptake value ratio and cognitive function was assessed in four cognitive domains 3 years after completion of trial treatments. Lower global sleep quality score (i.e., better sleep quality) correlated with lower cortical Pittsburgh compound-B standard uptake value ratio only in the tE2 group (r = 0.45, P = 0.047). Better global sleep quality also correlated with higher visual attention and executive function scores in the tE2 group (r = -0.54, P = 0.02) and in the oral conjugated equine estrogen group (r = -0.65, P = 0.005). Menopausal hormone therapies may influence the effects of sleep on cognitive function, specifically, visual attention and executive function. There also appears to be a complex relationship between sleep, menopausal hormone therapies, cortical amyloid-β accumulation and cognitive function, and tE2 formulation may modify the relationship between sleep and amyloid-β accumulation.

Introduction Ensuring adequate and equitable distribution of resources to support persons living with dementia relies on understanding the burden and distribution of dementia in a population. Our goal was to develop an approach to estimate dementia prevalence at the local level in the United States using publicly available data. Methods Our approach combines publicly available data on dementia prevalence and demographic data from the US Census to estimate dementia prevalence. We illustrate this approach by estimating dementia prevalence in persons aged 65 and older in Philadelphia, PA; Chicago, IL; and Atlanta, GA. Results Overall, we estimate the prevalence of dementia among those 65 and older to be 11.9% in Philadelphia, 11.8% Chicago, and 12.3% in Atlanta. Estimates across Philadelphia localities vary from 9.3% to 15.9%. Discussion Our approach provides a cost‐effective method to generate estimates of dementia prevalence at the local level. HIGHLIGHTS Brain health needs assessments require understanding of local dementia prevalence. Our approach can be used to estimate dementia prevalence in individual communities. This information can inform decisions about distribution of resources.

Introduction: Patients with poststroke cognitive impairment appear to be at higher risk of recurrent stroke and death. However, whether cognitive impairment after lacunar stroke is associated with recurrent stroke and death remains unclear. We assessed whether global or domain-specific cognitive impairment after lacunar stroke is associated with recurrent stroke and death. Methods: We considered patients from the Secondary Prevention of Small Subcortical Strokes (SPS3) trial with a baseline cognitive exam administered in English by certified SPS3 personnel, 14–180 days after qualifying lacunar stroke. We considered a baseline score of ≤86 on the Cognitive Assessment Screening Instrument to indicate global cognitive impairment, Results: The study included 1,528 participants with a median enrollment time of 62 days after qualifying stroke. During a mean follow-up of 3.9 years, 11.4% of participants had recurrent stroke and 8.2% died. In the fully adjusted models, memory impairment was independently associated with an increased risk of recurrent stroke (hazard ratio, 1.48; 95% confidence interval [95% CI]: 1.04–2.09) and death (hazard ratio, 1.87; 95% CI: 1.25–2.79). Global impairment (hazard ratio, 1.66; 95% CI: 1.06–2.59) and nonmemory impairment (hazard ratio, 1.74; 95% CI: 1.14–2.67) were associated with an increased risk of death. Discussion/Conclusion: After lacunar stroke, memory impairment was an independent predictor of recurrent stroke and death, while global and nonmemory impairment were associated with death. Cognitive screening in lacunar stroke may help identify populations at higher risk of recurrent stroke and death.

Cognitive reserve is inherently a dynamic construct; however, traditional methods of estimating reserve have focused on static proxy variables. A recently proposed psychometric approach entails modeling reserve as residual cognition not explained by demographic and brain variables. In this study, we extended this approach to longitudinal measurement and examined how change in reserve relates to clinical outcomes in late life and influences the effect of brain atrophy on cognitive decline. Results indicated that cognitive reserve changes were associated with progression of clinical diagnosis. More rapid depletion of cognitive reserve was associated with faster decline in non-memory cognitive functions, even after accounting for longitudinal brain atrophy. The effect of longitudinal brain atrophy on cognitive decline differed based on the extent to which an individual’s reserve changed. Whereas depletion of reserve appeared to unmask the effects of brain atrophy on cognitive decline, maintenance of reserve buffered against the negative effects of brain atrophy. Study results highlight that changes in reserve may have important implications for individual differences in cognitive aging trajectories.

ObjectiveThe effects of 2 frequently used formulations of menopausal hormone therapy (mHT) on brain structure and cognition were investigated 3 years after the end of a randomized, placebo-controlled trial in recently menopausal women with good cardiovascular health.MethodsParticipants (aged 42–56 years; 5–36 months past menopause) were randomized to one of the following: 0.45 mg/d oral conjugated equine estrogen (oCEE); 50 μg/d transdermal 17β-estradiol (tE2); or placebo pills and patch for 4 years. Oral progesterone (200 mg/d) was given to mHT groups for 12 days each month. MRIs were performed at baseline, at the end of 4 years of mHT, and 3 years after the end of mHT (n = 75). A subset of participants also underwent Pittsburgh compound B–PET (n = 68).ResultsVentricular volumes increased more in the oCEE group compared to placebo during the 4 years of mHT, but the increase in ventricular volumes was not different from placebo 3 years after the discontinuation of mHT. Increase in white matter hyperintensity volume was similar in the oCEE and tE2 groups, but it was statistically significantly greater than placebo only in the oCEE group. The longitudinal decline in dorsolateral prefrontal cortex volumes was less in the tE2 group compared to placebo, which correlated with lower cortical Pittsburgh compound B uptake. Rates of global cognitive change in mHT groups were not different from placebo.ConclusionsThe effects of oCEE on global brain structure during mHT subside after oCEE discontinuation but white matter hyperintensities continue to increase. The relative preservation of dorsolateral prefrontal cortical volume in the tE2 group over 7 years indicates that mHT may have long-term effects on the brain.Classification of evidenceThis study provides Class III evidence that the rates of change in global brain volumes and cognitive function in recently menopausal women receiving mHT (tE2 or oCEE) were not significantly different from women receiving placebo, as measured 3 years after exposure to mHT.

Longitudinal studies have steadily grown in popularity across the educational and behavioral sciences, particularly with the increased availability of technological devices that allow the easy collection of repeated measures on multiple dimensions of substantive relevance. This article discusses a procedure that can be used to evaluate population differences in within-person (intraindividual) variability in such longitudinal investigations. The method is based on an application of the latent variable modeling methodology within a two-level modeling framework. The approach is used to obtain point and interval estimates of the differences in within-person variance and in the strength of correlative effects of repeated measures between normal and very mildly demented persons in a longitudinal study of a diagnostic cognitive test assessing verbal episodic memory.

Cannabis is the most commonly-used drug in the US, with older adults being the fastest-growing group of users. National surveys among 50+ adults found poorer executive function among current or past cannabis users, but better performance with daily users. However, there is little evidence linking levels of cannabis use and subjective cognitive decline (SCD) among middle-age and older adults. This study sought to examine the association between levels of cannabis use in the past 30 days and SCD during the past 12 months using Behavioral Risk Factor Surveillance System (BRFSS) data (2016-2019) from 45+ individuals while controlling for demographics, chronic conditions, exercise, general and mental health. Logit models with SCD as outcome were estimated using complex survey weights. Multiple group analyses examined differences across age groups: 45-64 vs. 65+. Levels of cannabis use in the past 30 days were categorized as: no use, 1-4 days, 5-20 days; and 21-30 days. Adjusted results indicated that those who reported no cannabis use were from 35% to 47% less likely to report SCD compared to cannabis users at all levels: 1-4 days (OR=0.65, 95%CI=0.46, 0.92); 5-20 days (OR=0.53, 95%CI=0.36,0.78); 21-30 days (OR=.61, 95%CI=0.45,0.83). In multi-group analyses, levels of cannabis use effects on SCD remained statistically significant in the 45-64 age group, but not in the 65+ group. Further research targeting SCD is needed to design interventions particularly for middle-age cannabis users whose health has been compromised by disease or age-related vulnerabilities and are at greater risk for adverse cognitive outcomes from cannabis use.

This study highlights primary caregivers’ experiences with health department policies designed to support people with cognitive impairment/Alzheimer’s Disease and Related Dementias (ADRD). Caregivers were defined as individuals aged 45-85 that provide at least 10 hours of unpaid care. Five, 90-minute focus groups were conducted virtually with 24 caregivers of individuals with cognitive impairment/ADRD. Transcripts were analyzed thematically. Caregivers were primarily Black females (75%) with at least a high school education (42%). Care recipients were likely to be community-dwelling parents (71%), with moderate or advanced (79%) dementia. Caregivers described challenges with accessing resources intended for care recipients, especially as cognitive impairment worsened. Caregivers reported providing care 24/7 as traumatizing. Home-based personal aides and companionship services did not reduce this burden. COVID-19 impacted caregivers and care recipient’s access to resources increasing burden. Policies need to be flexible for ever-changing needs of individuals with ADRD and support the overall well-being of the caregivers.

Objectives: The purpose of this study was to investigate the longitudinal trajectory of self- and informant-subjective cognitive complaints (SCC), and to determine if SCC predict longitudinal changes in objective measures (OM) of cognitive function. Methods: The study included healthy and cognitively normal late middle-aged adults enriched with a family history of AD who were evaluated at up to three visits over a 4-year period. At each visit (Visit 1–3), self- and informant-SCC and OM were evaluated. Linear mixed models were used to determine if the longitudinal rate of change of self- and informant-SCC were associated with demographic variables, depressive symptoms, family history (FH), and apolipoprotein epsilon 4 (APOE4) status. The same modeling approach was used to examine the effect of Visit 1 SCC on longitudinal cognitive change after controlling for the same variables. Results: At Visit 1, more self-SCC were associated with fewer years of education and more depressive symptoms. SCC were also associated with poorer performance on cognitive measures, such that more self-SCC at Visit 1 were associated with poorer performance on memory and executive functioning measures at Visit 1, while more informant-SCC were associated with faster rate of longitudinal decline on a measure of episodic learning and memory. FH and APOE4 status were not associated with SCC. Discussion: Self- and informant-SCC showed an association with OM, albeit over different time frames in our late middle-aged sample. Additional longitudinal follow-up will likely assist in further clarifying these relationships as our sample ages and more pronounced cognitive changes eventually emerge. (JINS, 2017, 23, 617–626)

Introduction Family history (FH) of Alzheimer's disease (AD) affects mitochondrial function and may modulate effects of translocase of the outer mitochondrial membrane 40 kDa ( TOMM40 ) rs10524523 (‘523) poly-T length on memory decline. Methods For 912 nonapolipoprotein e4 middle-aged adults and 365 aged adults across the AD spectrum, linear mixed models gauged FH and TOMM40 ‘523 interactions on memory and global cognition between baseline and up to 10 years later. A cerebrospinal fluid mitochondrial function biomarker was also assessed. Results For FH negative participants, gene-dose preservation of memory and global cognition was seen for "very long" versus "short" carriers. For FH positive, an opposite gene-dose decline was seen for very long versus short carriers. Maternal FH was a stronger predictor in aged, but not middle-aged, participants. Similar gene-dose effects were seen for the mitochondrial biomarker aspartate aminotransferase. Discussion These results may clarify conflicting findings on TOMM40 poly-T length and AD-related decline.

Positive affect is associated with a number of health benefits; however, few studies have examined the relationship between positive affect and cerebral glucose metabolism, a key energy source for neuronal function and a possible index of brain health. We sought to determine if positive affect was associated with cerebral glucose metabolism in late middle-aged adults (n = 133). Participants completed the positive affect subscale of the Center for Epidemiological Studies Depression Scale at two time points over a two-year period and underwent 18F-fluorodeoxyglucose-positron emission tomography scanning. After controlling for age, sex, perceived health status, depressive symptoms, anti-depressant use, family history of Alzheimer's disease, APOE ε4 status and interval between visits, positive affect was associated with greater cerebral glucose metabolism across para-/limbic, frontal, temporal and parietal regions. Our findings provide evidence that positive affect in late midlife is associated with greater brain health in regions involved in affective processing and also known to be susceptible to early neuropathological processes. The current findings may have implications for interventions aimed at increasing positive affect to attenuate early neuropathological changes in at-risk individuals.

Copyright © 2016 The North American Menopause Society. Objective: The objective of the present study was to compare the efficacy of two forms of menopausal hormone therapy in alleviating vasomotor symptoms, insomnia, and irritability in early postmenopausal women during 4 years. Methods: A total of 727 women, aged 42 to 58, within 3 years of their final menstrual period, were randomized to receive oral conjugated estrogens (o-CEE) 0.45 mg (n = 230) or transdermal estradiol (t-E2) 50 μg (n = 225; both with micronized progesterone 200 mg for 12 d each mo), or placebos (PBOs; n= 275). Menopausal symptoms were recorded at screening and at 6, 12, 24, 36, and 48 months postrandomization. Differences in proportions of women with symptoms at baseline and at each follow-up time point were compared by treatment arm using exact x2tests in an intent-to-treat analysis. Differences in treatment effect by race/ethnicity and body mass index were tested using generalized linear mixed effects modeling. Results: Moderate to severe hot flashes (from 44% at baseline to 28.3% for PBO, 7.4% for t-E2, and 4.2% for o-CEE) and night sweats (from 35% at baseline to 19% for PBO, 5.3% for t-E2, and 4.7% for o-CEE) were reduced significantly by 6 months in women randomized to either active hormone compared with PBO (P < 0.001 for both symptoms), with no significant differences between the active treatment arms. Insomnia and irritability decreased from baseline to 6 months postrandomization in all groups. There was an intermittent reduction in insomnia in both active treatment arms versus PBO, with o-CEE being more effective than PBO at 36 and 48 months (P =0.002 and 0.05) and t-E2being more effective than PBO at 48 months (P = 0.004). Neither hormone treatment significantly affected irritability compared with PBO. Symptom relief for active treatment versus PBO was not significantly modified by body mass index or race/ethnicity. Conclusions: Recently postmenopausal women had similar and substantial reductions in hot flashes and night sweats with lower-than-conventional doses of oral or transdermal estrogen. These reductions were sustained during 4 years. Insomnia was intermittently reduced compared with PBO for both hormone regimens.

When assessments are primarily used to measure change over time, it is important to evaluate items according to their sensitivity to change, specifically. Items that demonstrate good sensitivity to between-person differences at baseline may not show good sensitivity to change over time, and vice versa. In this study, we applied a longitudinal factor model of change to a widely used cognitive test designed to assess global cognitive status in dementia, and contrasted the relative sensitivity of items to change. Statistically nested models were estimated introducing distinct latent factors related to initial status differences between test-takers and within-person latent change across successive time points of measurement. Models were estimated using all available longitudinal item-level data from the Alzheimer's Disease Assessment Scale-Cognitive subscale, including participants representing the full-spectrum of disease status who were enrolled in the multisite Alzheimer's Disease Neuroimaging Initiative. Five of the 13 Alzheimer's Disease Assessment Scale-Cognitive items demonstrated noticeably higher loadings with respect to sensitivity to change. Attending to performance change on only these 5 items yielded a clearer picture of cognitive decline more consistent with theoretical expectations in comparison to the full 13-item scale. Items that show good psychometric properties in cross-sectional studies are not necessarily the best items at measuring change over time, such as cognitive decline. Applications of the methodological approach described and illustrated in this study can advance our understanding regarding the types of items that best detect fine-grained early pathological changes in cognition. (PsycINFO Database Record

Changes in pituitary-ovarian hormones across the menopausal transition have multiple physiological consequences. However, little is known about how the major types of postmenopausal hormone therapy (HT) affect pituitary-ovarian hormonal relationships. This study evaluated these relationships in recently menopausal women (52.45 ± 2.49 yr of age) in the Kronos Early Estrogen Prevention Study (KEEPS) who were compliant to randomized, double-blinded treatment with oral conjugated equine estrogen (o-CEE; n = 109), transdermal 17β-estradiol (t-E2; n = 107), or placebo ( n = 146). Androstenedione, testosterone, 17β-estradiol, estrone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum before (baseline) and 48 mo after randomization to treatment. Descriptive summaries of hormone levels were performed, and multiple regression analyses were used to examine the effects of o-CEE, t-E2, and placebo on these hormone levels at 48 mo, adjusting for baseline levels. A network analysis examined the covariance of changes in hormone levels over the 48 mo within treatment groups. As expected, at 48 mo of treatment, hormone levels differed between women in the two active treatment groups compared with placebo, and network analysis indicated stronger relationships among hormone levels in the t-E2 and o-CEE groups compared with placebo. Associations among testosterone, 17β-estradiol, FSH, and LH differed between the o-CEE group compared with t-E2 and placebo groups. Thus, two common HT regimens differentially alter pituitary-ovarian hormone levels, altering feedback cycles and interhormonal associations in recently menopausal women. These interactions provide the basis for future studies investigating the impact of hormonal modulation of aging, including cognitive decline in women.

Parkinson’s disease (PD) is an age-related neurodegenerative disease that produces changes in movement, cognition, sleep, and autonomic function. Motor learning involves acquisition of new motor skills through practice, and is affected by PD. The purpose of the present study was to evaluate regional differences in resting cerebral blood flow (rCBF), measured using arterial spin labeling (ASL) MRI, during a finger-typing task of motor skill acquisition in PD patients compared to age- and gender-matched controls. Voxel-wise multiple linear regression models were used to examine the relationship between rCBF and several task variables, including initial speed, proficiency gain, and accuracy. In these models, a task-by-disease group interaction term was included to investigate where the relationship between rCBF and task performance was influenced by PD. At baseline, perfusion was lower in PD subjects than controls in the right occipital cortex. The task-by-disease group interaction for initial speed was significantly related to rCBF (p

Importance In the US, dementia risk is higher in non-Hispanic Black individuals than in non-Hispanic White individuals. To evaluate progress toward reducing such disparities, tracking secular trends in racial disparities in dementia prevalence is essential. Objective To examine whether relative racial disparities in dementia prevalence or incidence have changed in the US from 2000 to 2016. Design, Settings, and Participants The Health and Retirement Study (HRS) is a nationally representative study of adults 50 years or older. New participants are recruited every 6 years, and study visits occur biennially. Approximately 17 000 to 22 000 respondents have been surveyed at each wave since 2000, achieving response rates of 81% to 89%. Data for this cohort study were obtained from non-Hispanic White and non-Hispanic Black participants aged 70 years and older from the 2000 to 2016 waves. For analyses of secular trends in racial disparities in dementia prevalence, each HRS wave was considered separately (range of participants meeting eligibility criteria in each wave, 6322-7579). For analyses of secular trends in racial disparities in dementia incidence, 7 subcohorts were created (range of participants meeting eligibility criteria in each subcohort, 5322-5961) following up people without dementia for 4 years from subcohort baseline visits in 2000, 2002, 2004, 2006, 2008, 2010, and 2012. Data were analyzed from October 2019 to August 2020. Exposures Race based on self-response to closed-ended survey questions. Main Outcomes and Measures Dementia status was determined using 3 algorithms with similar sensitivity and specificity across non-Hispanic White and Black participants. Disparities were characterized using ratio measures. Results In this study, the mean age and percentage of male participants eligible for inclusion in analyses of racial disparities in dementia prevalence increased over time among non-Hispanic White participants (from 78.2 years and 40% in 2000 to 78.7 years and 44% in 2016) but remained steady in non-Hispanic Black participants during the same period (from 78.0 years and 37% in 2000 to 77.9 years and 38% in 2016). Prevalence ratios comparing Black and White participants ranged from approximately 1.5 to 1.9 across algorithms and years, whereas hazard ratios ranged from approximately 1.4 to 1.8. Although results suggest stable or declining dementia risk overall, there was no evidence suggesting change in relative racial disparities in dementia prevalence or incidence during follow-up. Conclusions and Relevance This study did not find evidence to suggest that the ratio of dementia risk across Black and White individuals changed in the US between 2000 and 2016. Additional efforts to identify and mitigate the source of these disparities is warranted.

Despite the clear and compelling association between social connections and well-being, the underlying mechanisms that help stave off adverse health impacts are not well understood, particularly among older adults in disadvantaged groups. Social relationships in older age may be instrumental for exchanging and gaining knowledge that further influence health and help increase awareness about misconceptions and lifestyle behaviors known to delay or reduce cognitive decline. This study used cross-sectional survey data from 147(aged 58-90 years; 75% female) low-income African American homebound community dwellers to investigate heterogeneity in dementia literacy profiles and its association with social connectedness. Eleven items (false=0, true=1, don’t know=2) from a validated instrument were used to measure dementia literacy (DL). The Lubben’s social network scale was used for a social connectedness construct. We employed a 2-stage latent class modeling approach to examine heterogeneity in DL and estimate the regressions among the derived classes and the predictors (social connectedness, education level and age). A 3-class model produced a reasonable fit and classification (entropy=0.852) of “dementia literacy patterns” labeled as (high-literacy:37%), moderate-literacy:45.2%), low-literacy:17.8%)). Social connectedness was highly predictive of class membership. A high level of social relationships increased the probability of being in the “high-dementia-literacy” class compared to the “low-dementia-literacy” class (OR=2.189, p=0.016). For a unit increase in social connectedness, the odds of being in the “high-dementia-literacy” class compared to the “low-dementia-literacy” class increased by a factor of 2.2. Tailored and focused interventions to reduce social disconnectedness may also help increase dementia awareness and reduce barriers to early diagnosis.

Physical/functional limitations are known to lead to loneliness, but there is little research on protective factors that may mediate their adverse association, particularly in vulnerable populations. This study used cross-sectional survey data from 147 (aged 58-90 years; 75% females) predominantly low-income African American homebound community dwellers to investigate the role of resilience and social connectedness in mediating the effect of physical/functional limitations on loneliness. Items from validated instruments were used to measure four latent variables (physical/functional limitations, resilience, loneliness and social connectedness). Structural parallel mediator models estimated each path in the mediation analysis controlling for gender, education, and age. Confidence intervals for mediation effects were generated via bias-corrected bootstrapping with 10,000 replications. The total effect of physical/functional limitations on perceived loneliness was significant. Social connectedness and resilience fully and significantly mediated the relationship between physical/functional limitations and loneliness. The indirect effect (B =.143; 95% CI = .047, .280) for the physical/functional limitations-resilience-loneliness pathway indicated that the positive effect of physical/functional limitations on loneliness was approximately 0.143 points lower as mediated by higher resilience. The indirect path of physical/functional limitations on loneliness through the mediation of social connectedness (B =.077; 95% CI = .010, .168) yielded a reduction of .077 points. The total amount of variance in feelings of loneliness accounted for by the overall model, which included the proposed mediators and control variables, was 48.6%. Interventions to build resilience and social interactions may attenuate the effects of physical/functional disability and loneliness on health outcomes in individuals at risk.

Objective Although at increased risk for developing dementia compared with white patients, older African Americans are diagnosed later in the course of dementia. Using the common sense model (CSM) of illness perception, we sought to clarify processes promoting timely diagnosis of mild cognitive impairment (MCI) for African American patients. Design, Setting, Participants In-person, cross-sectional survey data were obtained from 187 African American (mean age: 60.44 years). Data were collected at social and health-focused community events in three southern Wisconsin cities. Measurements The survey represented a compilation of published surveys querying CSM constructs focused on early detection of memory disorders, and willingness to discuss concerns about memory loss with healthcare providers. Derived CSM variables measuring perceived causes, consequences, and controllability of MCI were included in a structural equation model predicting the primary outcome: Willingness to discuss symptoms of MCI with a provider. Results Two CSM factors influenced willingness to discuss symptoms of MCI with providers: Anticipation of beneficial consequences and perception of low harm associated with an MCI diagnosis predicted participants' willingness to discuss concerns about cognitive changes. No association was found between perceived controllability and causes of MCI, and willingness to discuss symptoms with providers. Conclusions These data suggest that allaying concerns about the deleterious effects of a diagnosis, and raising awareness of potential benefits, couldinfluence an African American patient's willingness to discuss symptoms of MCI with a provider. The findings offer guidance to designers of culturally congruent MCI education materials, and healthcare providers caring for older African Americans.

Background The immune response in Alzheimer’s disease (AD) involves activation of microglia which may remove β-amyloid. However, overproduction of inflammatory compounds may exacerbate neural damage in Alzheimer’s disease. AD pathology accumulates years before diagnosis, yet the extent to which neuroinflammation is involved in the earliest disease stages is unknown.

Introduction Physical activity (PA) is associated with brain health in older adults. However, it is unknown whether the current physical activity recommendations (PAR) impart substantive benefit. The objective of this study was to compare temporal lobe volumes between older adults who met PAR and those who did not. Methods Ninety‐one enrollees from the Wisconsin Registry for Alzheimer's Prevention wore an accelerometer for seven consecutive days to quantify their PA behaviors and underwent a T‐1 anatomic magnetic resonance imaging scan. Participants were categorized as either having met PAR or not based on the US Department of Health and Human Services recommendations of 150 minutes of moderate‐to‐vigorous physical activity per week. Results Participants who met PAR possessed significantly greater inferior (η2P = .050) and anterior (η2P = .055) temporal lobe volumes compared with those who did not (P