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IntroductionWith Alzheimer's disease and related dementias (ADRD) representing an enormous public health challenge, there is a need to support individuals in learning about and addressing their modifiable risk factors (e.g., diet, sleep, and physical activity) to prevent or delay dementia onset. However, there is limited availability for evidence-informed tools that deliver both quality education and support for positive behavior change such as by increasing self-efficacy and personalizing goal setting. Tools that address the needs of Latino/a, at higher risk for ADRD, are even more scarce.MethodsWe established a multidisciplinary team to develop the Healthy Actions and Lifestyles to Avoid Dementia or Hispanos y el ALTo a la Demencia (HALT-AD) program, a bilingual online personalized platform to educate and motivate participants to modify their risk factors for dementia. Grounded in social cognitive theory and following a cultural adaptation framework with guidance from a community advisory board, we developed HALT-AD iteratively through several cycles of rapid prototype development, user-centered evaluation through pilot testing and community feedback, and refinement.ResultsUsing this iterative approach allowed for more than 100 improvements in the content, features, and design of HALT-AD to improve the program's usability and alignment with the interests and educational/behavior change support needs of its target audience. Illustrative examples of how pilot data and community feedback informed improvements are provided.DiscussionDeveloping HALT-AD iteratively required learning through trial and error and flexibility in workflows, contrary to traditional program development methods that rely on rigid, pre-set requirements. In addition to efficacy trials, studies are needed to identify mechanisms for effective behavior change, which might be culturally specific. Flexible and personalized educational offerings are likely to be important in modifying risk trajectories in ADRD.

ObjectiveSubjective cognitive decline (SCD) is a potential early risk marker for Alzheimer's disease (AD), but its utility may vary across individuals. We investigated the relationship of SCD severity with memory function and cerebral blood flow (CBF) in areas of the middle temporal lobe (MTL) in a cognitively normal and overall healthy sample of older adults. Exploratory analyses examined if the association of SCD severity with memory and MTL CBF was different in those with lower and higher cardiovascular disease (CVD) risk status.MethodsFifty-two community-dwelling older adults underwent magnetic resonance imaging, neuropsychological testing, and were administered the Everyday Cognition Scale (ECog) to measure SCD. Regression models investigated whether ECog scores were associated with memory performance and MTL CBF, followed by similar exploratory regressions stratified by CVD risk status (i.e., lower vs higher stroke risk).ResultsHigher ECog scores were associated with lower objective memory performance and lower entorhinal cortex CBF after adjusting for demographics and mood. In exploratory stratified analyses, these associations remained significant in the higher stroke risk group only.ConclusionsOur preliminary findings suggest that SCD severity is associated with cognition and brain markers of preclinical AD in otherwise healthy older adults with overall low CVD burden and that this relationship may be stronger for individuals with higher stroke risk, although larger studies with more diverse samples are needed to confirm these findings. Our results shed light on individual characteristics that may increase the utility of SCD as an early risk marker of cognitive decline.

ObjectivesPhysical activity (PA) may help maintain brain structure and function in aging. Since the intensity of PA needed to effect cognition and cerebrovascular health remains unknown, we examined associations between PA and cognition, regional white matter hyperintensities (WMH), and regional cerebral blood flow (CBF) in older adults.MethodForty-three older adults without cognitive impairment underwent magnetic resonance imaging (MRI) and comprehensive neuropsychological assessment. Waist-worn accelerometers objectively measured PA for approximately one week.ResultsHigher time spent in moderate to vigorous PA (MVPA) was uniquely associated with better memory and executive functioning after adjusting for all light PA. Higher MVPA was also uniquely associated with lower frontal WMH volume although the finding was no longer significant after additionally adjusting for age and accelerometer wear time. MVPA was not associated with CBF. Higher time spent in all light PA was uniquely associated with higher CBF but not with cognitive performance or WMH volume.ConclusionsEngaging in PA may be beneficial for cerebrovascular health, and MVPA in particular may help preserve memory and executive function in otherwise cognitively healthy older adults. There may be differential effects of engaging in lighter PA and MVPA on MRI markers of cerebrovascular health although this needs to be confirmed in future studies with larger samples. Future randomized controlled trials that increase PA are needed to elucidate cause-effect associations between PA and cerebrovascular health.

BackgroundExtensive research suggests that physical activity (PA) is important for brain and cognitive health and may help to delay or prevent Alzheimer's disease and related dementias. Most PA interventions designed to improve brain health in older adults have been conducted in laboratory, gym, or group settings that require extensive resources and travel to the study site or group sessions. Research is needed to develop novel interventions that leverage mobile health (mHealth) technologies to help older adults increase their engagement in PA in free-living environments, reducing participant burden and increasing generalizability of research findings. Moreover, promoting engagement in moderate-to-vigorous PA (MVPA) may be most beneficial to brain health; thus, using mHealth to help older adults increase time spent in MVPA in free-living environments may help to offset the burden of Alzheimer's disease and related dementias and improve quality of life in older age.ObjectiveWe developed a novel PA intervention that leverages mHealth to help older adults achieve more minutes of MVPA independently. This pilot study was a 12-week randomized controlled trial to investigate the feasibility of providing just-in-time (JIT) feedback about PA intensity during free-living exercise sessions to help older adults meet current PA recommendations (150 minutes per week of MVPA).MethodsParticipants were eligible if they were cognitively healthy English speakers aged between 65 and 80 years without major cardiovascular, neurologic, or mental health conditions; could ambulate independently; and undergo magnetic resonance imaging. Enrollment occurred from October 2017 to March 2020. Participants randomized to the PA condition received an individualized exercise prescription and an mHealth device that provided heart rate-based JIT feedback on PA intensity, allowing them to adjust their behavior in real time to maintain MVPA during exercise sessions. Participants assigned to the healthy aging education condition received a reading prescription consisting of healthy aging topics and completed weekly quizzes based on the materials.ResultsIn total, 44 participants were randomized to the intervention. A follow-up manuscript will describe the results of the intervention as well as discuss screening, recruitment, adverse events, and participants' opinions regarding their participation in the intervention.ConclusionsThe long-term goal of this intervention is to better understand how MVPA affects brain and cognitive health in the real world and extend laboratory findings to everyday life. This pilot randomized controlled trial was conducted to determine the feasibility of using JIT heart rate zone feedback to help older adults independently increase time spent in MVPA while collecting data on the plausible mechanisms of change (frontal and medial temporal cerebral blood flow and cardiorespiratory fitness) that may affect cognition (memory and executive function) to help refine a planned stage 2 behavioral trial.Trial registrationClinicalTrials.gov NCT03058146; https://clinicaltrials.gov/ct2/show/NCT03058146.International registered report identifier (irrid)DERR1-10.2196/42980.

ObjectivesDerive latent profiles of accelerometry-measured moderate-vigorous physical activity (MVPA) for Hispanic/Latino adults, examine associations between latent MVPA profiles and neurocognition, and describe profiles via self-reported MVPA.MethodsComplex survey design methods were applied to cross-sectional data from 7,672 adults ages 45-74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008-2011). MVPA was measured via hip-worn accelerometers. Latent profile analysis was applied to derive latent MVPA profiles (minutes/day of week). Neurocognition was assessed with the Brief-Spanish English Verbal Learning Test (B-SEVLT) Sum, B-SEVLT Recall, Controlled Oral Word Association Test (word fluency), and Digit Symbol Substitution (DSS) test. All tests were z-scored, and a global neurocognition score was generated by averaging across scores. Survey linear regression models were used to examine associations between latent MVPA profiles and neurocognitive measures. Self-reported MVPA domains were estimated (occupational, transportation, and recreational) for each latent profile.ResultsFour latent MVPA profiles from the overall adult target population (18-74 years) were derived and putatively labeled: No MVPA, low, moderate, and high. Only the high MVPA profile (compared to moderate) was associated with lower global neurocognition. Sensitivity analyses using latent MVPA profiles with only participants aged 45-74 years showed similar profiles, but no associations between latent MVPA profiles and neurocognition. The occupational MVPA domain led in all latent MVPA profiles.DiscussionWe found no consistent evidence to link accelerometry-measured MVPA profiles to neurocognitive function. Research to better characterize the role of high occupational MVPA in relation to neurocognition among Hispanic/Latino adults are needed.

ObjectiveWe recently demonstrated that relative to consensus-based methods, actuarial methods may improve diagnostic accuracy across the continuum of cognitively normal (CN), mild cognitive impairment (MCI), and dementia in the overall National Alzheimer's Coordinating Center (NACC) cohort. However, the generalizability and comparative utility of current methods of diagnosing MCI and dementia due to Alzheimer's disease and related disorders (ADRD) are significantly understudied in non-Hispanic Black (NHB) older adults. Thus, we extended our previous investigation to more specifically explore the utility of consensus-based and actuarial diagnostic methods in NHB older adults.Method: We compared baseline consensus and actuarial diagnostic rates, and associations of ratings of functioning with neuropsychological performance and diagnostic outcomes, in NHB (n = 963) and non-Hispanic White (NHW; n = 4577) older adults in the NACC cohort.Results: 60.0% of the NHB subsample, versus 29.2% of the NHW subsample, included participants who met actuarial criteria for MCI despite being classified as CN or impaired-not-MCI per consensus. Additionally, associations between ratings of functioning and neuropsychological performance were less consistent in NHB participants than in NHW participants.Conclusions: Our results provide evidence of differential degrees of association between reported functioning and neuropsychological performance in NHB and NHW older adults, which may contribute to racial group differences in diagnostic rates, and prompt consideration of the strengths and weaknesses of consensus-based and actuarial diagnostic approaches in assessing neurocognitive functioning in NHB older adults.

IntroductionDespite increased risk of cognitive decline in Hispanics/Latinos, research on early risk markers of Alzheimer's disease in this group is lacking. Subjective cognitive decline (SCD) may be an early risk marker of pathological aging. We investigated associations of SCD with objective cognition among a diverse sample of Hispanics/Latinos living in the United States.MethodsSCD was measured with the Everyday Cognition Short Form (ECog-12) and cognitive performance with a standardized battery in 6125 adults aged ≥ 50 years without mild cognitive impairment or dementia (x̄age  = 63.2 years, 54.5% women). Regression models interrogated associations of SCD with objective global, memory, and executive function scores.ResultsHigher SCD was associated with lower objective global (B = -0.16, SE = 0.01), memory (B = -0.13, SE = 0.02), and executive (B = -0.13, SE = 0.02, p's

BackgroundResearch suggests that physical activity (PA) has both acute and chronic beneficial effects on cognitive function in laboratory settings and under supervised conditions. Mobile health technologies make it possible to reliably measure PA and cognition in free-living environments, thus increasing generalizability and reach. Research is needed to determine whether the benefits of PA on cognitive function extend from the laboratory to real-world contexts.ObjectiveThis observational study aims to examine the association between daily fluctuations in PA and cognitive performance using mobile health technologies in free-living environments.MethodsA total of 90 adults (mean age 59, SD 6.3 years; 65/90, 72% men) with various comorbidities (eg, cardiovascular risk and HIV) and different levels of baseline cognition (ranging from cognitively normal to impaired) completed ecological momentary cognitive tests (EMCTs) on a smartphone twice daily while wearing an accelerometer to capture PA levels for 14 days. Linear mixed-effects models examined the daily associations of PA with executive function and verbal learning EMCTs. Moderation analyses investigated whether the relationship between daily PA and daily performance on EMCTs changed as a function of baseline cognition, cardiovascular risk, and functional status (independent vs dependent).ResultsDays with greater PA were associated with better (faster) performance on an executive function EMCT after covariate adjustment (estimate -0.013; β=-.16; P=.04). Moderation analyses (estimate 0.048; β=.58; P=.001) indicated that days with greater PA were associated with better (faster) executive function performance in individuals who were functionally dependent (effect size -0.53; P

IntroductionAlthough subjective cognitive decline (SCD) may be an early risk marker of Alzheimer's Disease (AD), research on SCD among Hispanics/Latinos/as/x (henceforth Latinos/as) living in the U.S. is lacking. We investigated if the cross-sectional relationship of self-reported SCD with objective cognition varies as a function of ethnic background (Latinos/as versus Non-Hispanic Whites [NHWs]). Secondary analyses conducted solely within the Latino/a group investigated if informant reported SCD is associated with objective cognition and whether self-reported SCD is related to markers of brain health in a sub-sample of Latinos/as with available MRI data.MethodsEighty-three participants (≥60 years of age) without dementia (35 Latinos/as; 48 NHWs) completed the Mattis Dementia Rating Scale (MDRS) and the Subjective Cognitive Decline-Questionnaire (SCD-Q). Additionally, 22 Latino/a informants completed the informant-version of the SCD-Q. Hierarchical regression models investigated if ethnicity moderates the association of MDRS and SCD-Q scores after adjusting for demographics and depressive symptoms. Correlational analyses within the Latino/a group investigated self- and informant-reported associations of SCD-Q scores with objective cognition, and associations of self-reported SCD-Q scores with medial temporal lobe volume and thickness.ResultsLatinos/as had lower education and MDRS scores than NHWs. Higher SCD-Q scores were associated with lower MDRS scores only in Latinos/as. Within the Latino/a group, self, but not informant reported SCD was related to objective cognition. Medium to large effect sizes were found whereby higher self-reported SCD was associated with lower entorhinal cortex thickness and left hippocampal volume in Latinos/as.ConclusionsThe association of SCD and concurrent objectively measured global cognition varied by ethnic background and was only significant in Latinos/as. Self-reported SCD may be an indicator of cognitive and brain health in Latinos/as without dementia, prompting clinicians to monitor cognition. Future studies should explore if SCD predicts objective cognitive decline in diverse groups of Latinos/as living in the U.S.

ObjectiveThe utility of informant-based measures of cognitive decline to accurately describe objective cognitive performance in Parkinson's disease (PD) without dementia is uncertain. Due to the clinical relevance of this information, the purpose of this study was to examine the relationship between informant-based reports of patient cognitive decline via the Informant Questionnaire of Cognitive Decline in the Elderly (IQCODE) and objective cognition in non-demented PD controlling for cognitive status (i.e., mild cognitive impairment; PD-MCI and normal cognition; PD-NC).MethodOne-hundred and thirty-nine non-demented PD participants (PD-MCI n = 38; PD-NC n = 101) were administered measures of language, executive function, attention, learning, delayed recall, visuospatial function, mood, and motor function. Each participant identified an informant to complete the IQCODE and a mood questionnaire.ResultsGreater levels of informant-based responses of patient cognitive decline on the IQCODE were significantly associated with worse objective performance on measures of global cognition, attention, learning, delayed recall, and executive function in the overall sample, above and beyond covariates and cognitive status. However, the IQCODE was not significantly associated with language or visuospatial function.ConclusionsResults indicate that informant responses, as measured by the IQCODE, may provide adequate information on a wide range of cognitive abilities in non-demented PD, including those with MCI and normal cognition. Findings have important clinical implications for the utility of the IQCODE in the identification of PD patients in need of further evaluation, monitoring, and treatment.

This study employed novel GPS methods to assess the effect of a multilevel physical activity (PA) intervention on device-measured walking locations in 305 community dwelling older adults, ages 65+ (mean age = 83, 73% women). Retirement communities were randomized to a 1-year PA intervention that encouraged neighborhood walking, or to a healthy aging control condition. Total time and time spent walking in four life-space domains were assessed using GPS and accelerometer devices. The intervention increased the time spent walking as a proportion of total time spent in the Campus, Neighborhood and Beyond Neighborhood domains. Intervention effects on walking location were observed in both genders and across physical and cognitive functioning groups. Results demonstrate that an intervention providing individual, social and environmental support for walking can increase PA in larger life-space domains for a broad spectrum of older adults.

IntroductionEpisodic learning and memory performance are crucial components of cognitive assessment. To meet the needs of a diverse Hispanic/Latino population, we aimed to provide normative data on the Brief Spanish-English Verbal Learning Test (B-SEVLT).MethodsThe target population for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) included individuals 45+ years old from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds. Average age was 56.5 years ± 9.92, 54.5% were female, and mean education was 11.0 years ± 5.6 (unweighted n = 9309). Participants were administered the B-SEVLT in their preferred language (Spanish or English). Hispanic/Latino background adjusted B-SEVLT scores and percentile cut-points were created using survey-adjusted regression models.ResultsHigher educational attainment, younger age, and being female were associated with higher learning and memory performance. Hispanic/Latino background groups differed in B-SEVLT performance.DiscussionRepresentative learning and memory norms for Hispanic/Latinos of diverse backgrounds will improve cognitive assessment and accuracy of neurocognitive disorder diagnosis.

Background: Healthy aging is critically important for several reasons, including economic impact and quality of life. As the population of older adults rapidly increases, identifying acceptable ways to promote healthy aging is a priority. Technologies that can facilitate health promotion and risk reduction behaviors may be a solution, but only if these mobile health (mHealth) tools can be used by the older adult population. Within the context of a physical activity intervention, this study gathered participant's opinions about the use of an mHealth device to learn about acceptance and to identify areas for improvement. Methods: The Independent Walking for Brain Health study (NCT03058146) was designed to evaluate the effectiveness of a wearable mHealth technology in facilitating adherence to a physical activity prescription among participants in free-living environments. An Exit Survey was conducted following intervention completion to gauge participant's perceptions and solicit feedback regarding the overall study design, including exercise promotion strategies and concerns specific to the technology (e.g., privacy), that could inform more acceptable mHealth interventions in the future. The Digital Health Checklist and Framework was used to guide the analysis focusing on the domains of Privacy, Access and Usability, and Data Management. Results: Participants (n = 41) were in their early 70's (mean = 71.6) and were predominantly female (75.6%) and White (92.7%). Most were college educated (16.9 years) and enjoyed using technology in their everyday life (85.4%). Key challenges included privacy concerns, device accuracy, usability, and data access. Specifically, participants want to know what is being learned about them and want control over how their identifiable data may be used. Overall, participants were able to use the device despite the design challenges. Conclusions: Understanding participant's perceptions of the challenges and concerns introduced by mHealth is important, as acceptance will influence adoption and adherence to the study protocol. While this study learned from participants at studycompletion, we recommend that researchers consider what might influence participant acceptance of the technology (access, data management, privacy, risks) and build these into the mHealth study design process. We provide recommendations for future mHealth studies with older adults.

The ε4 allele of the apolipoprotein E (APOE) gene, a risk factor for cognitive decline, is associated with alterations in medial temporal lobe (MTL) structure and function, yet little research has been dedicated to understanding how these alterations might interact to negatively impact cognition. To bridge this gap, the present study employed linear regression models to determine the extent to which APOE genotype (ε4+, ε4-) modifies interactive effects of baseline arterial spin labeling MRI-measured cerebral blood flow (CBF) and FreeSurfer-derived cortical thickness/volume (CT/Vo) in two MTL regions of interest (entorhinal cortex, hippocampus) on memory change in 98 older adults who were cognitively normal at baseline. Baseline entorhinal CBF was positively associated with memory change, but only among ε4 carriers with lower entorhinal CT. Similarly, baseline entorhinal CT was positively associated with memory change, but only among ε4 carriers with lower entorhinal CBF. Findings suggest that APOE ε4 carriers may experience concomitant alterations in neurovascular function and morphology in the MTL that interact to negatively affect cognition prior to the onset of overt clinical symptoms. Results also suggest the presence of distinct multimodal neural signatures in the entorhinal cortex that may signal relative risk for cognitive decline among this group, perhaps reflecting different stages of cerebrovascular compensation (early effective vs. later ineffective).

Recent stroke studies have shown that the ipsi-lesional thalamus longitudinally and significantly decreases after stroke in the acute and subacute stages. However, additional considerations in the chronic stages of stroke require exploration including time since stroke, gender, intracortical volume, aging, and lesion volume to better characterize thalamic differences after cortical infarct. This cross-sectional retrospective study quantified the ipsilesional and contralesional thalamus volume from 69 chronic stroke subjects' anatomical MRI data (age 35-92) and related the thalamus volume to time since stroke, gender, intracortical volume, age, and lesion volume. The ipsi-lesional thalamus volume was significantly smaller than the contra-lesional thalamus volume (t(68) = 13.89, p

OBJECTIVE:The ε4 allele of the apolipoprotein E (APOE) gene increases risk for cognitive decline in normal and pathologic aging. However, precisely how APOE ε4 exerts its negative impact on cognition is poorly understood. The present study aimed to determine whether APOE genotype (ε4+ vs. ε4-) modifies the interaction of medial temporal lobe (MTL) resting cerebral blood flow (CBF) and brain structure (cortical thickness [CT], volume [Vo]) on verbal memory performance. METHODS:Multiple linear regression models were employed to investigate relationships between APOE genotype, arterial spin labeling MRI-measured CBF and FreeSurfer-based CT and Vo in four MTL regions of interest (left and right entorhinal cortex and hippocampus), and verbal memory performance among a sample of 117 cognitively normal older adults (41 ε4+, 76 ε4-) between the ages of 64 and 89 (mean age ​= ​73). RESULTS:Results indicated that APOE genotype modified the interaction of CBF and CT on memory in the left entorhinal cortex, such that the relationship between entorhinal CBF and memory was negative (lower CBF was associated with better memory) in non-carriers with higher entorhinal CT, positive (higher CBF was associated with better memory) in non-carriers with lower entorhinal CT, and negative (higher CBF was associated with worse memory) in ε4 carriers with lower entorhinal CT. CONCLUSIONS:Findings suggest that older adult APOE ε4 carriers may experience vascular dysregulation and concomitant morphological alterations in the MTL that interact to negatively affect memory even in the absence overt clinical symptoms, providing potential insight into the mechanistic link between APOE ε4 and detriments in cognition. Moreover, findings suggest a distinct multimodal neural signature in ε4 carriers (higher CBF and lower CT in the entorhinal cortex) that could aid in the identification of candidates for future clinical trials aimed at preventing or slowing cognitive decline. Differential findings with respect to ε4 carriers and non-carriers are discussed in the context of neurovascular compensation.

ObjectiveThe authors investigated if the physical activity increases observed in the Multilevel Intervention for Physical Activity in Retirement Communities (MIPARC) improved cognitive functions in older adults. The authors also examined if within-person changes in moderate to vigorous physical activity (MVPA), as opposed to low-light and high-light physical activity, were related to cognitive improvements in the entire sample.MethodsThis was a cluster randomized control trial set in retirement communities in San Diego County, CA. A total of 307 older adults without a formal diagnosis of dementia (mean age: 83 years; age range: 67-100; standard deviation: 6.4 years; 72% women) were assigned to the physical activity (N = 151) or healthy education control (N = 156) groups. Interventions were led by study staff for the first 6 months and sustained by peer leaders for the next 6 months. Components included individual counseling and self-monitoring with pedometers, group education sessions, and printed materials. Measurements occurred at baseline, 6 months, and 12 months. Triaxial accelerometers measured physical activity for 1 week. The Trail Making Test (TMT) Parts A and B and a Symbol Search Test measured cognitive functions.ResultsThere were no significant differences in cognitive functions between the MIPARC intervention and control groups at 6 or 12 months. Within-person increases in MVPA, and not low-light or high-light physical activity, were associated with improvements in TMT Parts B, B-A, and Symbol Search scores in the entire sample.ConclusionFindings suggest that MVPA may have a stronger impact on cognitive functions than lower intensity physical activity within retirement community samples of highly educated older adults without dementia.

IntroductionAge-related decreases in cerebral blood flow (CBF) may lead to cognitive decline, while physical activity (PA) can maintain CBF and cognition in aging. The intensity of PA needed to affect CBF in aging, and the independent effects of sedentary time on CBF are currently unknown. Moreover, research conducted in free-living environments with objective measures of PA (e.g., accelerometry) is lacking.MethodsThis cross-sectional study used accelerometry to objectively measure sedentary time, all light PA [AllLightPA], moderate-to-vigorous PA [MVPA], and total activity counts [TAC] in 52 cognitively healthy older adults. Robust linear regressions investigated the association of CBF (using arterial spin labeling magnetic resonance imaging) in frontal and medial temporal regions, with each PA intensity and sedentary time.ResultsGreater sedentary time was significantly associated with lower CBF in lateral and medial frontal regions after adjusting for MVPA, while higher AllLightPA (adjusted for MVPA), MVPA (adjusted for AllLightPA), and TAC were associated with greater CBF in lateral and medial frontal regions.DiscussionLighter activities, as well as MVPA, are beneficial to CBF in brain regions typically affected by the aging process and malleable to exercise interventions (i.e., the frontal lobes), whereas sedentary time is an independent risk factor for neurovascular dysregulation in normal aging.

ObjectiveEvidence suggests that famous face naming may be a cognitive ability especially sensitive to the early pathological processes of Alzheimer's disease (AD) and that those at risk for AD may demonstrate a Ribot temporal gradient (RTG), characterized by better performance for naming remote famous faces than for naming recent famous faces. Reductions in cerebral blood flow (CBF) and gray matter volume (GMV) have been implicated in the neuropathological cascade of AD and show utility as biomarkers of AD risk. We examined whether a RTG during famous face naming was associated with lower CBF and/or GMV among a group of cognitively normal older adults.MethodsVoxel-wise independent samples t-tests were employed to contrast resting CBF values between those who exhibited a RTG (RTG+) during a famous face naming task and those who did not (RTG-) among a sample of 52 cognitively normal older adults (25 RTG-, 27 RTG+; mean age = 73). Groups were also compared on GMV using a voxel-wise general linear model.ResultsSignificant group differences in CBF and GMV were found, whereby the RTG+ group demonstrated reduced CBF and GMV within medial temporal lobe regions (hippocampus, parahippocampal gyrus), relative to the RTG- group.ConclusionsThis represents the first study to show that cognitively intact older adults who demonstrate a RTG during famous face naming exhibit vascular dysregulation and structural changes similar to that seen in AD risk. Findings suggest that famous face naming ability may be particularly sensitive to the very early brain changes associated with AD.

Cerebral blood flow (CBF) alterations and amyloid-β (Aβ) accumulation have been independently linked to cognitive deficits in older adults at risk for dementia. Less is known about how CBF and Aβ may interact to affect cognition in cognitively normal older adults. Therefore, we examined potential statistical interactions between CBF and Aβ status in regions typically affected in Alzheimer's disease (AD) within a sample of older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Sixty-two cognitively normal participants (mean age = 72 years) underwent neuroimaging and memory testing. Arterial spin labeling magnetic resonance imaging was used to quantify CBF and florbetapir PET amyloid imaging was used to measure Aβ deposition. Aβ status (i.e., positivity versus negativity) was determined based on established cutoffs (Landau et al., 2013). The Rey Auditory Verbal Learning Test was used to assess memory. Linear regression models adjusted for age, education, and sex, demonstrated significant interactions between CBF and Aβ status on memory performance. Among Aβ positive older adults, there were significant negative associations between higher CBF in hippocampus, posterior cingulate, and precuneus and poorer memory performance. In contrast, among Aβ negative older adults, there were no significant associations between CBF and cognition. Our findings extend previous CBF studies of dementia risk by reporting interactions between Aβ status and CBF on memory performance in a sample of well-characterized, cognitively normal older adults. Results suggest that differential CBF-cognition associations can be identified in healthy, asymptomatic Aβ positive older adults relative to Aβ negative individuals. Associations between higherCBF and poorer memory among Aβ positive older adults may reflect a cellular and/or vascular compensatory response to pathologic processes whereby higher CBF is needed to maintain normal memory abilities. Findings indicate that CBF and its associations with cognition may have utility as a reliable marker of brain function early in the AD process when interventions are likely to be beneficial.

Age-related changes in cerebral blood flow (CBF), which carries necessary nutrients to the brain, are associated with increased risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Whether the association between CBF and cognition is moderated by apolipoprotein E (ApoE) ε4 genotype, a known risk factor for AD, remains understudied, with most research focusing on exploring brain regions in which there are diagnostic group differences in CBF (i.e., cognitively normal vs. MCI vs. AD). This study measured resting CBF via arterial spin labeling (ASL) magnetic resonance imaging (MRI) and verbal memory functions using a composite score in 59 older adults with normal cognition (38 ε3; 21 ε4). Linear mixed effect models were employed to investigate if the voxel-wise relationship between verbal memory performance and resting CBF was modified by ApoE genotype. Results indicated that carriers of the ApoE ε4 allele display negative associations between verbal memory functions and CBF in medial frontal cortex, medial and lateral temporal cortex, parietal regions, insula, and the basal ganglia. Contrarily, ε3 carriers exhibited positive associations between verbal memory functions and CBF in medial frontal cortex, thalamus, insula, and basal ganglia. Findings suggest that higher CBF was associated with worse verbal memory functions in cognitively normal ε4 carriers, perhaps reflecting dysregulation within the neurovascular unit, which is no longer supportive of cognition. Results are discussed within the context of the vascular theory of AD risk.

Psychological and psychosocial resources, including resilience and social support, have traditionally been studied in the context of the stress paradigm and, more recently, in the context of successful aging. This study used moderated mediation analyses to examine the role of perceived stress in the relationships between physical and mental health functioning and self-rated successful aging (SRSA) and whether differences between people in level of resilience and social support changes the role of perceived stress in these relationships. A cross-sectional study of 1,006 older adults (mean age: 77 years) completed scales addressing SRSA, physical and mental health functioning, perceived stress, resilience, and social support. Results indicated that the strength of relationships between both physical and mental health functioning and SRSA were reduced after accounting for variation in level of perceived stress. The role of perceived stress in the association between mental health functioning and SRSA was found to be stronger among participants with the highest levels of resilience, and the influence of perceived stress on the degree of relationship between physical health functioning and SRSA was stronger among those with greatest social support. These findings suggest that interventions to reduce perceived stress may help break the link between disability and poor well-being in older adults. The findings further suggest that the impact of such interventions might differ depending on psychological resources (i.e., resilience) for mental health disabilities and external resources (i.e., social support) for those with physical health problems. The complex interplay of these factors should be taken into account in clinical settings.

ObjectiveWhether subjective cognitive complaints are suggestive of depression or concurrent cognitive impairment in older adults without dementia remains unclear. The current study examined this question in a large (N = 1000), randomly selected, community-based sample of adults aged 51 to 99 years without a formal diagnosis of dementia (Successful AGing Evaluation [SAGE] study).MethodsThe modified Telephone Interview for Cognitive Status (TICS-m) measured objective cognitive function, the Cognitive Failures Questionnaire (CFQ) measured subjective cognitive complaints, and the 9-item Patient Health Questionnaire (PHQ-9) measured depression. Spearman ρ correlations and linear regression models were conducted to examine the relationship among variables in the baseline SAGE sample.ResultsThere was a weak association between TICS-m and CFQ scores (ρ = -.12); however, a moderate to large association was observed for CFQ and PHQ-9 (ρ = .44). Scores on the CFQ were not associated with TICS-m scores (β = -.03, P = .42) after controlling for PHQ-9 and variables of interest, such as age, gender, ethnicity, and physical functioning, while PHQ-9 was significantly associated with CFQ scores (β = .46, P < .001) after controlling for variables of interest.ConclusionsSubjective cognitive complaints are more likely related to symptoms of depression rather than concurrent cognitive impairment in a large cross-section of community-dwelling adults without a formal diagnosis of dementia.

Resting cerebral blood flow (CBF) decreases with age; however regulatory increases in hippocampal CBF have been associated with genetic risk (Apolipoprotein E [APOE] ε4 carriers) for Alzheimer's disease (AD). Although physical activity exerts beneficial effects on CBF in healthy elderly, the effects of sedentary behaviors on CBF remain unknown. We measured resting hippocampal CBF (via arterial spin labeling magnetic resonance imaging) and sedentary time/physical activity (via accelerometry) on 33 cognitively healthy adults (ages 52-81), 9 of which were APOE ε4 carriers. Results indicate that the relationship between sedentary time and CBF in the left hippocampus differs by APOE status, whereby APOE ε4 carriers show higher CBF as a function of longer sedentary time (B = 10.8, SE = 3.17, β = 0.74, t = 3.41, p < 0.01) compared to noncarriers (B = 1.4, SE = 2.7, β = 0.096, t = 0.51, p = 0.61), possibly suggesting a CBF regulatory response to compensate for metabolic alterations in dementia risk. These preliminary data suggest that the relationship between CBF and sedentary time is different in APOE ε4 carriers and noncarriers and that sedentary time may act as a behavioral risk factor for CBF dysregulation in those at genetic risk for developing AD. More research is needed to further understand the role of sedentary behaviors and physical activity on CBF, especially in individuals at genetic risk of developing AD.

Vascular risk factors and cerebral blood flow (CBF) reduction have been linked to increased risk of cognitive impairment and Alzheimer's disease (AD); however the possible moderating effects of age and vascular risk burden on CBF in late life remain understudied. We examined the relationships among elevated vascular risk burden, age, CBF, and cognition. Seventy-one non-demented older adults completed an arterial spin labeling MR scan, neuropsychological assessment, and medical history interview. Relationships among vascular risk burden, age, and CBF were examined in a priori regions of interest (ROIs) previously implicated in aging and AD. Interaction effects indicated that, among older adults with elevated vascular risk burden (i.e., multiple vascular risk factors), advancing age was significantly associated with reduced cortical CBF whereas there was no such relationship for those with low vascular risk burden (i.e., no or one vascular risk factor). This pattern was observed in cortical ROIs including medial temporal (hippocampus, parahippocampal gyrus, uncus), inferior parietal (supramarginal gyrus, inferior parietal lobule, angular gyrus), and frontal (anterior cingulate, middle frontal gyrus, medial frontal gyrus) cortices. Furthermore, among those with elevated vascular risk, reduced CBF was associated with poorer cognitive performance. Such findings suggest that older adults with elevated vascular risk burden may be particularly vulnerable to cognitive change as a function of CBF reductions. Findings support the use of CBF as a potential biomarker in preclinical AD and suggest that vascular risk burden and regionally-specific CBF changes may contribute to differential age-related cognitive declines.

Neurocognitive impairment and metabolic syndrome (MetS) are prevalent in persons with HIV (PWH). We examined disparities in HIV-associated neurocognitive function between Hispanic and non-Hispanic White older PWH, and the role of MetS in explaining these disparities. Participants included 116 community-dwelling PWH aged 50–75 years enrolled in a cohort study in southern California [58 Hispanic (53% Spanish speaking) and 58 age-comparable non-Hispanic White; overall group: age: M = 57.9, standard deviation (SD) = 5.7; education (years): M = 13, SD = 3.4; 83% male, 58% AIDS, 94% on antiretroviral therapy]. Global neurocognition was derived from T-scores adjusted for demographics (age, education, sex, ethnicity, language) on a battery of 10 cognitive tests. MetS was ascertained via standard criteria that considered central obesity, and fasting elevated triglycerides, low high-density lipoprotein cholesterol and elevated glucose, or medical treatment for these conditions. Covariates examined included sociodemographic, psychiatric, substance use and HIV disease characteristics. Compared with non-Hispanic Whites, Hispanics showed worse global neurocognitive function (Cohen's d = 0.56, p < 0.05) and had higher rates of MetS (38% vs. 56%, p < 0.05). A stepwise regression model including ethnicity and significant covariates showed Hispanic ethnicity was the sole significant predictor of worse global neurocognition (B = −3.82, SE = 1.27, p < 0.01). A model also including MetS showed that both Hispanic ethnicity (B = −3.39, SE = 1.31, p = 0.01) and MetS (B = −2.73, SE = 1.31, p = 0.04) were independently associated with worse neurocognition. In conclusion, findings indicate that increased MetS is associated with worse neurocognitive function in both Hispanic and non-Hispanic White older PWH, but does not explain neurocognitive disparities. MetS remains an important target for intervention efforts to ameliorate neurocognitive dysfunction among diverse older PWH. [ABSTRACT FROM AUTHOR]

Objective: Emotional functioning is linked to HIV-associated neurocognitive impairment, yet research on this association among diverse people with HIV (PWH) is scant. We examined emotional health and its association with neurocognition in Hispanic and White PWH. Methods: Participants included 107 Hispanic (41% primarily Spanish-speakers; 80% Mexican heritage/origin) and 216 White PWH (Overall age: M = 53.62, SD = 12.19; 86% male; 63% AIDS; 92% on antiretroviral therapy). Emotional health was assessed via the National Institute of Health Toolbox (NIHTB)-Emotion Battery, which yields T-scores for three factor-based summary scores (negative affect, social satisfaction, and psychological well-being) and 13 individual component scales. Neurocognition was measured via demographically adjusted fluid cognition T-scores from the NIHTB-cognition battery. Results: 27%–39% of the sample had problematic socioemotional summary scores. Hispanic PWH showed less loneliness, better social satisfaction, higher meaning and purpose, and better psychological well-being than Whites (ps <.05). Within Hispanics, Spanish-speakers showed better meaning and purpose, higher psychological well-being summary score, less anger hostility, but greater fear affect than English speakers. Only in Whites, worse negative affect (fear affect, perceived stress, and sadness) was associated with worse neurocognition (p <.05); and in both groups, worse social satisfaction (emotional support, friendship, and perceived rejection) was linked with worse neurocognition (p <.05). Conclusion: Adverse emotional health is common among PWH, with subgroups of Hispanics showing relative strengths in some domains. Aspects of emotional health differentially relate to neurocogntition among PWH and cross-culturally. Understanding these varying associations is an important step towards the development of culturally relevant interventions that promote neurocognitive health among Hispanic PWH. [ABSTRACT FROM AUTHOR]

Background: Extensive research suggests that physical activity (PA) is important for brain and cognitive health and may help to delay or prevent Alzheimer's disease and related dementias. Most PA interventions designed to improve brain health in older adults have been conducted in laboratory, gym, or group settings that require extensive resources and travel to the study site or group sessions. Research is needed to develop novel interventions that leverage mobile health (mHealth) technologies to help older adults increase their engagement in PA in free-living environments, reducing participant burden and increasing generalizability of research findings. Moreover, promoting engagement in moderate-to-vigorous PA (MVPA) may be most beneficial to brain health; thus, using mHealth to help older adults increase time spent in MVPA in free-living environments may help to offset the burden of Alzheimer's disease and related dementias and improve quality of life in older age. Objective: We developed a novel PA intervention that leverages mHealth to help older adults achieve more minutes of MVPA independently. This pilot study was a 12-week randomized controlled trial to investigate the feasibility of providing just-in-time (JIT) feedback about PA intensity during free-living exercise sessions to help older adults meet current PA recommendations (150 minutes per week of MVPA). Methods: Participants were eligible if they were cognitively healthy English speakers aged between 65 and 80 years without major cardiovascular, neurologic, or mental health conditions; could ambulate independently; and undergo magnetic resonance imaging. Enrollment occurred from October 2017 to March 2020. Participants randomized to the PA condition received an individualized exercise prescription and an mHealth device that provided heart rate-based JIT feedback on PA intensity, allowing them to adjust their behavior in real time to maintain MVPA during exercise sessions. Participants assigned to the healthy aging education condition received a reading prescription consisting of healthy aging topics and completed weekly quizzes based on the materials. Results: In total, 44 participants were randomized to the intervention. A follow-up manuscript will describe the results of the intervention as well as discuss screening, recruitment, adverse events, and participants' opinions regarding their participation in the intervention. Conclusions: The long-term goal of this intervention is to better understand how MVPA affects brain and cognitive health in the real world and extend laboratory findings to everyday life. This pilot randomized controlled trial was conducted to determine the feasibility of using JIT heart rate zone feedback to help older adults independently increase time spent in MVPA while collecting data on the plausible mechanisms of change (frontal and medial temporal cerebral blood flow and cardiorespiratory fitness) that may affect cognition (memory and executive function) to help refine a planned stage 2 behavioral trial. [ABSTRACT FROM AUTHOR]

Evidence suggests the ɛ4 allele of the apolipoprotein E (APOE) gene may accelerate an age-related process of cortical thickening and cerebral blood flow (CBF) reduction in the anterior cingulate cortex (ACC). Although the neural basis of this association remains unclear, evidence suggests it might reflect early neurodegenerative processes. However, to date, associations between cerebrospinal fluid (CSF) biomarkers of neurodegeneration, such as CSF tau, and APOE-related alterations in ACC cortical thickness (CTH) and CBF have yet to be explored. The current study explored the interaction of CSF tau and APOE genotype (ɛ4+, ɛ4-) on FreeSurfer-derived CTH and arterial spin labeling MRI-measured resting CBF in the ACC (caudal ACC [cACC] and rostral ACC [rACC]) among a sample of 45 cognitively normal older adults. Secondary analyses also examined associations between APOE, CTH/CBF, and cognitive performance. In the cACC, higher CSF tau was associated with higher CTH and lower CBF in ɛ4+, whereas these relationships were not evident in ɛ4-. In the rACC, higher CSF tau was associated with higher CTH for both ɛ4+ and ɛ4-, and with lower CBF only in ɛ4+. Significant interactions of CSF tau and APOE on CTH/CBF were not observed in two posterior reference regions implicated in Alzheimer's disease. Secondary analyses revealed a negative relationship between cACC CTH and executive functioning in ɛ4+ and a positive relationship in ɛ4-. Findings suggest the presence of an ɛ4-related pattern of increased CTH and reduced CBF in the ACC that is associated with biomarkers of neurodegeneration and subtle decrements in cognition. [ABSTRACT FROM AUTHOR]