Age and sex differences in the genetic architecture of measures of subjective health: Relationships with physical health, depressive symptoms, and episodic memory.

OBJECTIVES: Subjective health (SH) is not just an indicator of physical health, but also reflects active cognitive processing of information about one's own health and has been associated with emotional health measures, such as neuroticism and depression. Behavior genetic approaches investigate the genetic architecture of SH, i.e., genetic and environmental influences on individual differences in SH and associations with potential components such as physical, cognitive, and emotional health. Previous twin analyses have been limited by sex, sample size, age range, and focus on single covariates. METHODS: The current analysis used data from 24,173 adults ranging in age from 40-90 years from the international Interplay of Genes and Environment Across Multiple Studies (IGEMS) consortium to investigate the genetic architecture of three measures of SH: self-rated health, health compared to others, and impact of health on activities. Independent pathways model of SH included physical health, depressive symptoms, and episodic memory, with age, sex, and country included as covariates. RESULTS: Most or all of the genetic variance for SH measures was shared with physical health, depressive symptoms, and episodic memory. Genetic architecture of SH differed across measures, age groups (40-65, 66-90), and sexes. Age comparisons indicated stronger correlations with all 3 covariates in older adults, often resulting from greater shared genetic variance. DISCUSSION: The predictive value of SH has been amply demonstrated. The higher genetic contributions to associations between SH and its components in older adults support the increasing conceptualization with age of SH as an intuitive summation of one's vital reserve.

Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls.

BACKGROUND: Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults. METHODS: The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid ß (Aß) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls. RESULTS: The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aß, tau, or p-tau levels, or tau/Aß or p-tau/Aß ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (ß, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up. CONCLUSIONS: During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aß) changes or greater cognitive decline.

Elevated Amyloid-ß PET Scan and Cognitive and Functional Decline in Mild Cognitive Impairment and Dementia of Uncertain Etiology.

BACKGROUND: Elevated amyloid-ß (Aß) on positron emission tomography (PET) scan is used to aid diagnosis of Alzheimer's disease (AD), but many prior studies have focused on patients with a typical AD phenotype such as amnestic mild cognitive impairment (MCI). Little is known about whether elevated Aß on PET scan predicts rate of cognitive and functional decline among those with MCI or dementia that is clinically less typical of early AD, thus leading to etiologic uncertainty. OBJECTIVE: We aimed to investigate whether elevated Aß on PET scan predicts cognitive and functional decline over an 18-month period in those with MCI or dementia of uncertain etiology. METHODS: In 1,028 individuals with MCI or dementia of uncertain etiology, we evaluated the association between elevated Aß on PET scan and change on a telephone cognitive status measure administered to the participant and change in everyday function as reported by their care partner. RESULTS: Individuals with either MCI or dementia and elevated Aß (66.6% of the sample) showed greater cognitive decline compared to those without elevated Aß on PET scan, whose cognition was relatively stable over 18 months. Those with either MCI or dementia and elevated Aß were also reported to have greater functional decline compared to those without elevated Aß, even though the latter group showed significant care partner-reported functional decline over time. CONCLUSIONS: Elevated Aß on PET scan can be helpful in predicting rates of both cognitive and functional decline, even among cognitively impaired individuals with atypical presentations of AD.

Preventing cognitive decline by reducing BP target (PCOT): A randomized, pragmatic, multi-health systems clinical trial.

BACKGROUND: Growing evidence suggests that intensive lowering of systolic blood pressure (BP) may prevent mild cognitive impairment (MCI) and dementia. However, current guidelines provide inconsistent recommendations regarding optimal BP targets, citing safety concerns of excessive BP lowering in the diverse population of older adults. We are conducting a pragmatic trial to determine if an implementation strategy to reduce systolic BP to <130 and diastolic BP to <80 mmHg will safely slow cognitive decline in older adults with hypertension when compared to patients receiving usual care. METHODS: The Preventing Cognitive Decline by Reducing BP Target Trial (PCOT) is an embedded randomized pragmatic clinical trial in 4000 patients from two diverse health-systems who are age ≥ 70 years with BP >130/80 mmHg. Participants are randomized to the intervention arm or usual care using a permuted block randomization within each health system. The intervention is a combination of team-based care with clinical decision support to lower home BP to <130/80 mmHg. The primary outcome is cognitive decline as determined by the change in the modified Telephone Interview for Cognitive Status (TICS-m) scores from baseline. As a secondary outcome, patients who decline ≥3 points on the TICS-m will complete additional cognitive assessments and this information will be reviewed by an expert panel to determine if they meet criteria for MCI or dementia. CONCLUSION: The PCOT trial will address the effectiveness and safety of hypertension treatment in two large health systems to lower BP targets to reduce risk of cognitive decline in real-world settings.

Care partners experience of an oral health intervention for individuals with mild cognitive impairment and mild dementia using behavior change technique: A qualitative study.

Oral health declines in older adults with cognitive impairment. We aimed to improve oral hygiene outcomes for individuals with mild cognitive impairment (MCI) or mild dementia (MD) by fostering behavior changes among carepartners assisting them. We used qualitative data of verbatim transcripts of coaching sessions with carepartners (n = 17 dyads:10 dyads for MCI, 7 dyads for MD). Directed and emergent coding were used to understand behavior change techniques (BCTs). BCTs were compared with carepartners of participants with MCI and MD. Most frequently used BCTs in both groups: prompts and cues, instruction on how to perform the behavior, review behavioral goal, and problem solving. Different BCTs emerged in study: social support-unspecified of the MCI group and credible source for MD group. Findings clarified active intervention components, common BCTs used by carepartners, and different BCT approaches for both participants. Findings help to elucidate the mechanisms of changes in individuals' behaviors in these interventions.

Association between results of an amyloid PET scan and healthcare utilization in individuals with cognitive impairment.

BACKGROUND: The Imaging Dementia Evidence for Amyloid Scanning (IDEAS) study reports that amyloid PET scans help providers diagnose and manage Alzheimer's disease and related dementias (ADRD). Using CARE-IDEAS, an IDEAS supplemental study, we examined the association between amyloid PET scan result (elevated or non-elevated amyloid), patient characteristics, and participant healthcare utilization. METHODS: We linked respondents in CARE-IDEAS study to their Medicare fee-for-service records (n = 1333). We examined participants' cognitive impairment-related, outpatient, emergency department (ED), and inpatient encounters in the year before compared with the 2 years after the amyloid PET scan. RESULTS: Individuals with a non-elevated amyloid scan had more healthcare encounters throughout the overall study period than those with an elevated amyloid scan. Regardless of the amyloid scan result, cognitive impairment-related and outpatient encounters overall decreased, but ED and inpatient encounters increased in the 2 years after the scan compared with the year prior. There was minimal evidence of differences in healthcare utilization between participants with an elevated and non-elevated amyloid scan. CONCLUSIONS: There is no difference in change in healthcare utilization between people with scans showing elevated and non-elevated beta-amyloid.

An Early and Unequal Decline: Life Course Trajectories of Cognitive Aging in the United States.

Objectives: Cognitive aging is a lifelong process with implications for Alzheimer's disease and dementia. This study aims to fill major gaps in research on the natural history of and social disparities in aging-related cognitive decline over the life span. Methods: We conducted integrative data analysis of four large U.S. population-based longitudinal studies of individuals aged 12 to 105 followed over two decades and modeled age trajectories of cognitive function in multiple domains. Results: We found evidence for the onset of cognitive decline in the 4th decade of life, varying gender differences with age, and persistent disadvantage among non-Hispanic Blacks, Hispanics, and those without college education. We further found improvement in cognitive function across 20th century birth cohorts but widening social inequalities in more recent cohorts. Discussion: These findings advance an understanding of early life origins of dementia risk and invite future research on strategies for promoting cognitive health for all Americans.

Comparing the Experiences of Participants With Mild Cognitive Impairment and Mild Dementia During an Oral Health Intervention.

Background and Objectives: Cognitive impairment is associated with poor oral health outcomes. Oral hygiene tasks are an essential target of interventions aiming to improve oral health for older adults with cognitive impairment. We aimed to examine whether experiences in an oral health intervention based on the Adaptive Leadership Framework for Chronic Illness differed between individuals with mild cognitive impairment (MCI) or mild dementia (MD) and their respective care partners. Research Design and Methods: This was a secondary analysis using directed content analysis and then an interpretive-description approach to analyze the data from a theory-driven intervention study. We included 10 people with MCI and their care partners (n = 20) and 8 people with MD and their care partners (n = 16) in the treatment arm of the intervention. For each participant, we analyzed audio recordings of 4 intervention coaching sessions, each ranging between 30 and 45 min. We managed the data and coding using ATLAS.TI software. Results: Participants in both the MCI and MD groups experienced similar challenges in adapting to changes in oral hygiene techniques, and both groups worked on learning new oral hygiene techniques taught by the dental hygienist and meeting individualized goals developed with their care partner, interventionist, and hygienist. On the other hand, there were subtle differences in technical challenges between participants in MCI and MD groups; participants in the MCI group reacted more actively to dental hygienist suggestions than the MD group. Discussion and Implications: Study findings provide information about how researchers and clinicians might tailor interventions to meet the learning needs of individuals and care partners in each group.

Associations Between Traumatic Brain Injury and Cognitive Decline Among Older Male Veterans: A Twin Study.

BACKGROUND AND OBJECTIVES: Traumatic brain injuries (TBIs) are associated with increased risk of dementia, but whether lifetime TBI influences cognitive trajectories in later life is less clear. Cognitive interventions after TBI may improve cognitive trajectories and delay dementia. Because twins share many genes and environmental factors, we capitalize on the twin study design to examine the association between lifetime TBI and cognitive decline. METHODS: Participants were members of the National Academy of Sciences-National Research Council's Twin Registry of male veterans of World War II with self or proxy-reported history of TBI and with up to 4 observations over 12 years of the modified Telephone Interview for Cognitive Status (TICS-m). We used linear random-effects mixed models to analyze the association between TBI and TICS-m in the full sample and among co-twins discordant for TBI. Additional TBI predictor variables included number of TBIs, severity (loss of consciousness [LOC]), and age of first TBI (age <25 vs 25+ years [older age TBI]). Models were adjusted for age (centered at 70 years), age-squared, education, wave, twin pair, lifestyle behaviors, and medical conditions. RESULTS: Of 8,662 participants, 25% reported TBI. History of any TBI (ß = -0.56, 95% CI -0.73 to -0.39), TBI with LOC (ß = -0.51, 95% CI -0.71 to -0.31), and older age TBI (ß = -0.66, 95% CI -0.90 to -0.42) were associated with lower TICS-m scores at 70 years. TBI with LOC (ß = -0.03, 95% CI -0.05 to -0.001), more than one TBI (ß = -0.05, 95% CI -0.09 to -0.002,), and older age TBI (ß = -0.06, 95% CI -0.09 to -0.03) were associated with faster cognitive decline. Among monozygotic pairs discordant for TBI (589 pairs), history of any TBI (ß = -0.55, 95% CI -0.91 to -0.19) and older age TBI (ß = -0.74, 95% CI -1.22 to -0.26) were associated with lower TICS-m scores at 70 years. Those with more than one TBI (ß = -0.13, 95% CI -0.23 to -0.03) and older age TBI (ß = -0.07, 95% CI -0.13 to -0.002) showed greater cognitive decline compared with their co-twin without TBI. DISCUSSION: These findings support an association of the effect of TBI on cognitive score and the rapidity of cognitive decline in later life. The results in monozygotic pairs, who share all genes and many exposures, particularly in early life, provide additional evidence of a causal relationship between TBI and poorer late-life cognitive outcomes.

Patient Cognitive Status and Physician Recommendations for Cardiovascular Disease Treatment: Results of Two Nationwide, Randomized Survey Studies.

BACKGROUND: Clinical guidelines recommend that older patients (65+) with mild cognitive impairment (MCI) and early-stage dementia receive similar guideline-concordant care after cardiovascular disease (CVD) events as those with normal cognition (NC). However, older patients with MCI and dementia receive less care for CVD and other conditions than those with NC. Whether physician recommendations for guideline-concordant treatments after two common CVD events, acute myocardial infarction (AMI) and acute ischemic stroke (stroke), differ between older patients with NC, MCI, and early-stage dementia is unknown. OBJECTIVE: To test the influence of patient cognitive status (NC, MCI, early-stage dementia) on physicians' recommendations for guideline-concordant treatments for AMI and stroke. DESIGN: We conducted two parallel, randomized survey studies for AMI and stroke in the US using clinical vignettes where the hypothetical patient's cognitive status was randomized between physicians. PARTICIPANTS: The study included cardiologists, neurologists, and generalists who care for most patients hospitalized for AMI and stroke. MAIN MEASURES: The primary outcome was a composite quality score representing the number of five guideline-concordant treatments physicians recommended for a hypothetical patient after AMI or stroke. KEY RESULTS: 1,031 physicians completed the study (58.5% response rate). Of 1,031 respondents, 980 physicians had complete information. After adjusting for physician factors, physicians recommended similar treatments after AMI and stroke in hypothetical patients with pre-existing MCI (adjusted ratio of expected composite quality score, 0.98 [95% CI, 0.94, 1.02]; P = 0.36) as hypothetical patients with NC. Physicians recommended fewer treatments to hypothetical patients with pre-existing early-stage dementia than to hypothetical patients with NC (adjusted ratio of expected composite quality score, 0.90 [0.86, 0.94]; P < 0.001). CONCLUSION: In these randomized survey studies, physicians recommended fewer guideline-concordant AMI and stroke treatments to hypothetical patients with early-stage dementia than those with NC. We did not find evidence that physicians recommend fewer treatments to hypothetical patients with MCI than those with NC.

Remember This: Age Moderation of Genetic and Environmental Contributions to Verbal Episodic Memory from Midlife through Late Adulthood.

It is well documented that memory is heritable and that older adults tend to have poorer memory performance than younger adults. However, whether the magnitudes of genetic and environmental contributions to late-life verbal episodic memory ability differ from those at earlier ages remains unresolved. Twins from 12 studies participating in the Interplay of Genes and Environment in Multiple Studies (IGEMS) consortium constituted the analytic sample. Verbal episodic memory was assessed with immediate word list recall (N = 35,204 individuals; 21,792 twin pairs) and prose recall (N = 3,805 individuals; 2,028 twin pairs), with scores harmonized across studies. Average test performance was lower in successively older age groups for both measures. Twin models found significant age moderation for both measures, with total inter-individual variance increasing significantly with age, although it was not possible definitively to attribute the increase specifically to either genetic or environmental sources. Pooled results across all 12 studies were compared to results where we successively dropped each study (leave-one-out) to assure results were not due to an outlier. We conclude the models indicated an overall increase in variance for verbal episodic memory that was driven by a combination of increases in the genetic and nonshared environmental parameters that were not independently statistically significant. In contrast to reported results for other cognitive domains, differences in environmental exposures are comparatively important for verbal episodic memory, especially word list learning.

Prevalence and incidence of depressive symptoms and diagnosis of depression as associated with elevated amyloid among Medicare beneficiaries with cognitive impairment.

BACKGROUND: Depression and cognitive impairment commonly co-occur, and it has been hypothesized that the two share pathological processes. Our objective for this study was to determine the relationship between elevated ß-amyloid level and the prevalence and incidence of depressive symptoms and diagnosed depression over two years among fee-for-service Medicare beneficiaries with cognitive impairment. METHODS: We utilized data from the CARE-IDEAS cohort study (N = 2078) including two measures of depressive symptoms (PHQ-2) and administrative claims data to identify pre-scan and incident depression diagnosis in subsample of fee-for-service Medicare beneficiaries (N = 1443). We used descriptive statistics and Poisson regression models with robust covariance. RESULTS: Beneficiaries whose scan results indicated not-elevated ß-amyloid were significantly more likely to have been diagnosed with depression pre-scan (46.4 % vs. 33.1 %). There was no significant association between elevated amyloid and the incidence of depressive symptoms or diagnosed depression. LIMITATIONS: The sample was limited to Medicare beneficiaries with cognitive impairment. Race/ethnic composition and education levels were not representative of the general population and there was substantial loss to follow-up. Mixed depressive / anxious episodes were captured as diagnoses of depression, potentially overestimating depression in this population. CONCLUSIONS: There was a high prevalence and incidence of diagnosed depression in this cohort of Medicare beneficiaries, but the incidence of depressive symptoms and diagnosed depression was not associated with elevated ß-amyloid.

Influence of mild cognitive impairment on patient and care partner decision-making for acute ischemic stroke.

GOALS: Evidence suggests that patients with mild cognitive impairment (MCI) receive fewer treatments for acute ischemic stroke and other cardiovascular diseases than patients with normal cognition. Little is known about how patient and care partner preferences for ischemic stroke treatment differ between the patient population with MCI and the population with normal cognition. This study aimed to understand how patient MCI diagnosis influences patient and care partner decision-making for acute ischemic stroke treatments. METHODS: Multi-center qualitative study using in-person semi-structured interviews with 20 MCI and normal cognition patient-care partner dyads using a standard guide. The present study reports results on patient and care partner preferences for a clinical vignette patient to receive three non-invasive treatments (intravenous tissue plasminogen activator, inpatient rehabilitation, and secondary preventive medications) and two invasive treatments (feeding tube and carotid endarterectomy) after acute ischemic stroke. We used qualitative content analysis to identify themes. FINDINGS: We identified three major themes: (1) Patients with MCI desired non-invasive treatments after stroke, similar to patients with normal cognition and for similar reasons; (2) Patients with MCI expressed different preferences than patients with normal cognition for two invasive treatments after stroke: carotid endarterectomy and feeding tube placement; and (3) Patients with MCI expressed more skepticism of the stroke treatment options and less decisiveness in decision-making than patients with normal cognition. CONCLUSIONS: These results suggest that patient MCI diagnosis may contribute to differences in patient and care partner preferences for invasive treatments after stroke, but not for non-invasive treatments.

Systematic Review, Meta-Analysis, and Population Attributable Risk of Dementia Associated with Traumatic Brain Injury in Civilians and Veterans.

Traumatic brain injury (TBI) is an established risk factor for dementia. However, the magnitude of risk is highly variable across studies. Identification of sub-populations at highest risk, with careful consideration of potential sources of bias, is urgently needed to guide public health policy and research into mechanisms and treatments. We conducted a systematic review and meta-analysis of risk of all-cause dementia after all-severity TBI. We assessed for effect of participant age and sex, veteran status, research methods, and region. The search window covered January 1990 to January 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Thirty-two studies met inclusion criteria. Data were pooled using random effects models. Population attributable risk (PAR) of dementia due to TBI in the U.S. was calculated by sex and veteran status. Pooled risk ratio (RR) for dementia after TBI was 1.66 (95% confidence interval 1.42-1.93). Younger age, male sex, and studies from Asia were associated with significantly higher risk; veteran status was not. Risk of dementia associated with "head injury/trauma" was not significantly different from that associated with "TBI" diagnosis specifically. PAR of dementia due to TBI among U.S. veterans was twice that of the general U.S. population, largely due to the high prevalence of TBI exposure in the majority male veteran population. This meta-analysis found that TBI is associated with nearly 70% increased risk of dementia. Risk may be highest among younger adults, men, and cohorts in Asia. Efforts to prevent TBI and also to prevent post-TBI dementia are of high importance. Additionally, improved methods for diagnosing and tracking TBI on a public health level, such as national registries, may improve the quality and generalizability of future epidemiological studies investigating the association between TBI and dementia.

The Preventing Alzheimer's with Cognitive Training (PACT) randomized clinical trial.

BACKGROUND: To address the rising prevalence of Alzheimer's disease and related dementias, effective interventions that can be widely disseminated are warranted. The Preventing Alzheimer's with Cognitive Training study (PACT) investigates a commercially available computerized cognitive training program targeting improved Useful Field of View Training (UFOVT) performance. The primary goal is to test the effectiveness of UFOVT to reduce incidence of clinically defined mild cognitive impairment (MCI) or dementia with a secondary objective to examine if effects are moderated by plasma ß-amyloid level or apolipoprotein E e4 (APOE e4) allele status. METHODS/DESIGN: This multisite study utilizes a randomized, controlled experimental design with blinded assessors and investigators. Individuals who are 65 years of age and older are recruited from the community. Eligible participants who demonstrate intact cognitive status (Montreal Cognitive Assessment score > 25) are randomized and asked to complete 45 sessions of either a commercially available computerized-cognitive training program (UFOVT) or computerized games across 2.5 years. After three years, participants are screened for cognitive decline. For those demonstrating decline or who are part of a random subsample, a comprehensive neuropsychological assessment is completed. Those who perform below a pre-specified level are asked to complete a clinical evaluation, including an MRI, to ascertain clinical diagnosis of normal cognition, MCI, or dementia. Participants are asked to provide blood samples for analyses of Alzheimer's disease related biomarkers. DISCUSSION: The PACT study addresses the rapidly increasing prevalence of dementia. Computerized cognitive training may provide a non-pharmaceutical option for reducing incidence of MCI or dementia to improve public health. REGISTRATION: The PACT study is registered at http://Clinicaltrials.govNCT03848312.

Advance directives among cognitively impaired persons who had an amyloid PET scan and their care partners: a mixed-methods study.

BACKGROUND: Little research exists on the role of ß-amyloid PET scans as part of Alzheimer's diagnostic tests and documentation of end-of-life preferences for persons with cognitive impairment. The study objectives were to examine the association of amyloid PET scan results (elevated vs. not elevated amyloid levels) and diagnostic category (mild cognitive impairment vs. dementia) with the likelihood of having an advance directive (reported a median of 4.5 months post-scan); to explore perceptions of PET scan results and their influence on planning for the future among persons with cognitive impairment and their care partners. METHODS: Sequential, explanatory mixed-methods design using data from dyads in the CARE-IDEAS study: advance directives as a factor of diagnostic category and scan result using multivariable logistic regression models; thematic analysis of semi-structured interviews with persons with cognitive impairment and care partners to explore how scan results influenced documentation of future healthcare preferences. Participants included 1784 persons with cognitive impairment and care partners from the CARE-IDEAS study, and a subsample of 100 semi-structured telephone interviews. RESULTS: 81.6% of dyads reported an advance directive. Non-Hispanic, White participants had higher rates of advance directives. There was no significant association between having an advance directive and scan results. Qualitative analysis provided insight into perceived urgency to have advance directives, evolving healthcare preferences, and the context of completing advance directives. CONCLUSIONS: Although amyloid PET scans prompted persons with cognitive impairment and care partners to consider progressive cognitive impairment as part of evolving healthcare preferences, we found substantial variability in the perceived urgency of documentation.

Amyloid-ß PET Scan Results Disclosure and Care-Partner Emotional Well-Being Over Time.

BACKGROUND: Diagnostic tests, such as amyloid-ß positron emission tomography (PET) scans, can increase appropriate therapeutic management for the underlying causes of cognitive decline. To evaluate the full utility of this diagnostic tool, information is needed on whether results from amyloid-ß PET scans influence care-partner outcomes. OBJECTIVE: This study examines the extent to which previous disclosure of elevated amyloid (suggestive of Alzheimer's disease (AD) etiology) versus not-elevated amyloid (not suggestive of AD etiology) is associated with changes in care-partner wellbeing. METHODS: The study used data derived from a national longitudinal survey of Medicare beneficiaries (n = 921) with mild cognitive impairment (MCI) or dementia and their care-partners. Care-partner wellbeing outcomes included depressive symptoms (PHQ-8), subjective burden (4-item Zarit burden score), and a 3-item measure of loneliness. Change was measured between 4 (Time 1) and 18 (Time 2) months after receiving the scan results. Adjusted linear regression models regressed change (Time 2-Time 1) in each outcome on scan result. RESULTS: Care-partners were primarily white, non-Hispanic, college-educated, and married to the care recipient. Elevated amyloid was not associated with statistically significant Time 1 differences in outcomes or with statistically significant changes in depressive symptoms 0.22 (-0.18, 0.61), subjective burden 0.36 (-0.01, 0.73), or loneliness 0.15 (-0.01, 0.32) for care-partners from one time point to another. CONCLUSION: Given advances in AD biomarker testing, future research in more diverse samples is needed to understand the influence of scan results on care-partner wellbeing across populations.

Lifecourse Traumatic Events and Cognitive Aging in the Health and Retirement Study.

INTRODUCTION: Much of the heterogeneity in the rate of cognitive decline and the age of dementia onset remains unexplained, and there is compelling data supporting psychosocial stressors as important risk factors. However, the literature has yet to come to a consensus on whether there is a causal relationship and, if there is, its direction and strength. This study estimates the relationship between lifecourse traumatic events and cognitive trajectories and predicted dementia incidence. METHODS: Using data on 7,785 participants aged ≥65 years from the Health and Retirement Study, this study estimated the association between lifecourse experience of 10 traumatic events (e.g., losing a child) and trajectories of Telephone Interview for Cognitive Status from 2006 to 2016 using linear mixed-effects models and predicted incident dementia from 2006 to 2014 using cumulative incidence functions (data analysis was in 2020-2022). Inverse probability weights accounted for loss to follow-up and confounding by sex, education, race/ethnicity, and age. RESULTS: Experiencing 1 or more traumatic events over the lifecourse was associated with accelerated decline compared with experiencing no events (e.g., ß= -0.05 [95% CI= -0.07, -0.02] Health and Retirement Study-Telephone Interview for Cognitive Status units/year; 1 vs 0 events). In contrast, experiencing traumatic events was associated with better cognitive function cross-sectionally. Furthermore, the impact of trauma on cognitive decline was of greater magnitude when it occurred after the age of 64 years. However, the magnitude and direction of association varied by the specific traumatic event. There were no associations with predicted incident dementia. CONCLUSIONS: These results suggest that researchers and clinicians should not aggregate traumatic events for understanding the risk of accelerated cognitive decline.

Nutrition state of science and dementia prevention: recommendations of the Nutrition for Dementia Prevention Working Group.

Observational studies suggest that nutritional factors have a potential cognitive benefit. However, systematic reviews of randomised trials of dietary and nutritional supplements have reported largely null effects on cognitive outcomes and have highlighted study inconsistencies and other limitations. In this Personal View, the Nutrition for Dementia Prevention Working Group presents what we consider to be limitations in the existing nutrition clinical trials for dementia prevention. On the basis of this evidence, we propose recommendations for incorporating dietary patterns and the use of genetic, and nutrition assessment tools, biomarkers, and novel clinical trial designs to guide future trial developments. Nutrition-based research has unique challenges that could require testing both more personalised interventions in targeted risk subgroups, identified by nutritional and other biomarkers, and large-scale and pragmatic study designs for more generalisable public health interventions across diverse populations.

"Now at least we have something to call it": Patient and care partner experiences receiving an amyloid PET scan.

BACKGROUND: The primary objective of this paper was to examine perspectives and experiences of individuals with cognitive impairment who received an amyloid PET scan and their care partners, with regard to the process, logistics, and decision-making associated with receiving an amyloid PET scan and its results. METHODS: Structured telephone interviews were conducted with 200 randomly sampled scan recipient/care partner dyads from the CARE IDEAS study. The audio-recorded, transcribed responses were analyzed using an inductive qualitative content analytic approach. RESULTS: Participating individuals and care partners described their experiences in seeking a diagnosis for memory issues, including decision-making and logistics involved with receiving an amyloid PET scan. Participants discussed the factors contributing to their decision to seek a diagnosis for their memory issues and their hopes and expectations in completing the scan. Participants also described the trajectory of this process, and although some described relatively straightforward trajectories, others described problems associated with identifying appropriate providers and coordinating care across numerous providers to obtain a diagnosis for their memory issues. Participants described an additional challenge of physicians attributing cognitive decline to normal aging, rather than signs of a neurodegenerative disorder. CONCLUSIONS: Findings shed light on the barriers and delays that individuals and care partners experience in connecting with physicians and obtaining a comprehensive evaluation for cognitive problems. Results from this study have implications for physicians who provide care to older adults, and specifically highlight the need for greater care coordination and clearer communication with and systems of referral for patients.