Cerebral arteriolosclerosis, lacunar infarcts, and cognition in older Black adults.

INTRODUCTION: Older Black adults are at risk of cerebral small vessel disease (CSVD), which contributes to dementia risk. Two subtypes of CSVD, arteriolosclerosis and ischemic lacunar infarcts, have been independently linked to lower cognition and higher dementia risk, but their combined effects on cognition in older Black adults are unclear. METHODS: Mixed models were used to examine the associations of in vivo measures of arteriolosclerosis (ARTS) and ischemic lacunar infarcts to cognitive level and change in 370 older Black adults without dementia.  RESULTS: Modeled together, higher ARTS load accounted for lower levels of global cognition, episodic memory, semantic memory, and perceptual speed, whereas higher infarct load accounted for lower levels of working memory. There were no associations with rate of cognitive change. DISCUSSION: Both arteriolosclerosis and ischemic infarcts impact the cognitive health of older Black adults, but arteriolosclerosis affects cognition more broadly and offers promise as an in vivo biomarker of dementia risk. HIGHLIGHTS: Older Black adults are at risk of cerebral small vessel disease (CSVD) and dementia. Examined magnetic resonance imaging-derived measure of arteriolosclerosis (ARTS), infarcts, and cognition. ARTS load was widely associated with lower cognition after adjusting for infarct load. Infarct load was specifically associated with lower complex attention. More within-Black in vivo studies of CSVD subtypes and cognition are needed.

Factors Associated With Healthcare and Financial Decision Making Among Older Black Adults Without Dementia.

OBJECTIVES: The study aims to identify factors associated with health care and financial decision-making among older Black adults without dementia. METHODS: Participants (N = 326) underwent assessments of decision-making and completed measurements of factors from four categories: cognitive, contextual, psychosocial, and personality. We performed separate linear regression models to examine the association between each factor and decision-making and created a fully adjusted model. RESULTS: Higher global cognition (estimate = 1.92, SE = 0.21, p < .0001) was associated with better decision-making. Contextual factors including higher current annual income (estimate = 0.23, SE = 0.05, p < .0001), higher childhood socioeconomic status (estimate = 0.48, SE = 0.18, p = .006), higher health and financial literacy (estimate = 0.08, SE = 0.01, p < .0001), and lower financial stress (estimate = -0.19, SE = 0.07, p = .01) were associated with better decision-making. More psychological well-being (estimate = 0.07, SE = 0.22, p = .001), a psychosocial factor, and less neuroticism (estimate = -0.06, SE = 0.02, p = .002), a personality factor, were associated with better decision-making. In the fully adjusted model, two factors, higher global cognition and higher literacy (health and financial), remained associated with better decision-making. CONCLUSIONS: Cognitive and contextual factors serve as drivers of decision-making among older Black adults. CLINICAL IMPLICATIONS: Clinicians may implement strategies to bolster cognition and improve health and financial literacy to facilitate optimal decision-making among older Black adults.

Central autonomic network dysfunction and plasma Alzheimer's disease biomarkers in older adults.

BACKGROUND: Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer's disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults. METHODS: Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aß42, Aß40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed. RESULTS: All autonomic networks were positively associated with Aß42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected. CONCLUSION: The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aß42/40, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.

Ethical, legal, and policy challenges in field-based neuroimaging research using emerging portable MRI technologies: guidance for investigators and for oversight.

Researchers are rapidly developing and deploying highly portable MRI technology to conduct field-based research. The new technology will widen access to include new investigators in remote and unconventional settings and will facilitate greater inclusion of rural, economically disadvantaged, and historically underrepresented populations. To address the ethical, legal, and societal issues raised by highly accessible and portable MRI, an interdisciplinary Working Group (WG) engaged in a multi-year structured process of analysis and consensus building, informed by empirical research on the perspectives of experts and the general public. This article presents the WG's consensus recommendations. These recommendations address technology quality control, design and oversight of research, including safety of research participants and others in the scanning environment, engagement of diverse participants, therapeutic misconception, use of artificial intelligence algorithms to acquire and analyze MRI data, data privacy and security, return of results and managing incidental findings, and research participant data access and control.

Procrastination, depressive symptomatology, and loneliness in later life.

OBJECTIVES: Procrastination is an almost universal behaviour and yet little research to date has focused on procrastination among older adults. The purpose of this study was to explore the potential association between age and procrastination, and the potential mediating roles of depressive symptomatology and loneliness. METHOD: Structural equation modelling was applied to data from 1309 participants (aged 29-92) from two waves United States Health and Retirement Study (2016-2020). Within the model, sex, education, marital status, and job status were added as covariates. RESULTS: There was no statistically significant direct effect between age and procrastination (ß = 0.06, p = 0.106). However, an indirect effect was present via depressive symptomatology (ß = -0.40, p < 0.001). No mediating effect of loneliness was observed (ß = - 0.01, p = 0.371). Subsequent analysis revealed that the symptoms, fatigue, loneliness, and lack of motivation significantly predicted procrastination. CONCLUSION: While age was not directly associated with procrastination, increasing age was associated with a decreased likelihood of depressive symptomatology, which was in turn associated with an increased likelihood of procrastination. Such findings indicates that age demonstrates no association with procrastination because of the suppressing effect of depressive symptomatology.

Subjective Age Moderates the Relationship Between Global Cognition and Susceptibility to Scams.

This study examined the interactive effect of subjective age on the relationship between global cognition and susceptibility to scams. Sixty-five participants underwent an assessment of global cognition (Mini Mental State Examination; MMSE), reported their perceived age (i.e., subjective age), and responded to a self-report questionnaire assessing scam susceptibility. A main effect of global cognition on scam susceptibility was found (p = .028); there was no main effect of subjective age (p = .819). An interaction between global cognition and subjective age was found (p = .016). Examination of conditional effects demonstrated that the relationship between cognition and scam susceptibility was not significant amongst those with subjective ages below one standard deviation of the mean, but was significant for those whose subjective ages fell around or above the mean. Findings suggest that individuals with older subjective ages may be particularly vulnerable to the negative effects of lower cognition on scam susceptibility.

Relationship of Decisional Conflict About Driving Habits Between Older Adult Drivers and Their Family Members and Close Friends.

This study examines the relationship of decisional conflict about driving habits between older adult drivers (≥70 years old) and their family members and close friends. This secondary analysis utilizes data originating from a multi-site randomized controlled trial assessing the effect of a driving decision aid (DDA) intervention. Decisional conflict about stopping or changing driving habits for drivers was measured with the Decisional Conflict Scale (DCS). Dyadic associations between drivers' and study partners' (SPs') DCS scores were analyzed using an actor-partner interdependence model. Among 228 driver-SP dyads, Dyadic DCS was correlated at baseline (r = .18, p < .01), and pre-intervention DCS was associated with post-intervention DCS (p < .001 for SPs [ß = .73] and drivers [ß = .73]). Drivers' baseline DCS and SPs' post-intervention DCS were slighly correlated (ß = .10; p = .036). Higher decisional conflict about driving among older drivers is frequently shared by their SPs. Shared decisional conflict may persist beyond intervening to support decision-making about driving cessation.

Comprehensive Older Adult and Caregiver Help (COACH): A person-centered caregiver intervention prevents elder mistreatment.

BACKGROUND: Elder mistreatment (EM) harms individuals, families, communities, and society as a whole. Yet research on interventions is lagging, and no rigorous studies demonstrating effective prevention have been published. This pilot study examines whether a first-of-its-kind coaching intervention reduced the experience of EM among older adults with chronic health conditions, including dementia. METHODS: We used a double-blind, randomized controlled trial to test a strengths-based person-centered caregiver support intervention, developed from evidence-based approaches used in other types of family violence. Participants (n = 80), family caregivers of older adults who were members of Kaiser Permanente, completed surveys at baseline, post-test, and 3-month follow-up. The primary outcome was caregiver-reported EM; additional proximal outcomes were caregiver burden, quality-of-life, anxiety, and depression. Nonparametric tests (Mann-Whitney U, Fisher's Exact, Wilcoxon Signed Rank, and McNemar's) were used to make comparisons between treatment and control groups and across time points. RESULTS: The treatment group had no EM after intervention completion (assessed at 3-month follow-up), a significantly lower rate than the control group (treatment = 0%, control = 23.1%, p = 0.010). CONCLUSIONS: In this pilot study, we found that the COACH caregiver support intervention successfully reduced EM of persons living with chronic illness, including dementia. Next steps will include: (1) testing the intervention's mechanism in a fully powered RCT and (2) scaling the intervention for testing in a variety of care delivery systems.

Financial Risk Aversion Among Older Black and White Adults.

OBJECTIVES: Risk aversion has a substantial impact on decision making and is associated with key demographic characteristics. However, few studies have investigated whether risk aversion varies by race. METHODS: We investigated racial differences in financial risk aversion in 684 older Black and White adults without dementia in the Minority Aging Research Study and Rush Memory and Aging Project matched for age, education, sex, and cognition using Mahalanobis distance. We also investigated whether select contextual factors (self-reported discrimination, socioeconomic status, and literacy) mediated or affective factors (trust, loneliness, and neuroticism) moderated any observed racial differences. RESULTS: In regression models adjusted for age, education, sex, and cognitive function, older Black adults were more risk averse than older White adults (Beta = 0.1264, standard error = 0.0227, p value ≤ .00001). None of the contextual or affective factors mediated or moderated this association. DISCUSSION: Older Black adults are more financially risk averse than older White adults. Because risk aversion may be associated with important financial and health outcomes in older age, more research is needed to investigate the reasons for this difference.

CogDrisk, ANU-ADRI, CAIDE, and LIBRA Risk Scores for Estimating Dementia Risk.

Importance: While the Australian National University-Alzheimer Disease Risk Index (ANU-ADRI), Cardiovascular Risk Factors, Aging, and Dementia (CAIDE), and Lifestyle for Brain Health (LIBRA) dementia risk tools have been widely used, a large body of new evidence has emerged since their publication. Recently, Cognitive Health and Dementia Risk Index (CogDrisk) and CogDrisk for Alzheimer disease (CogDrisk-AD) risk tools have been developed for the assessment of dementia and AD risk, respectively, using contemporary evidence; comparison of the relative performance of these risk tools is limited. Objective: To evaluate the performance of CogDrisk, ANU-ADRI, CAIDE, LIBRA, and modified LIBRA (LIBRA with age and sex estimates from ANU-ADRI) in estimating dementia and AD risks (with CogDrisk-AD and ANU-ADRI). Design, Setting, and Participants: This population-based cohort study obtained data from the Rush Memory and Aging Project (MAP), the Cardiovascular Health Study Cognition Study (CHS-CS), and the Health and Retirement Study-Aging, Demographics and Memory Study (HRS-ADAMS). Participants who were free of dementia at baseline were included. The factors were component variables in the risk tools that included self-reported baseline demographics, medical risk factors, and lifestyle habits. The study was conducted between November 2021 and March 2023, and statistical analysis was performed from January to June 2023. Main outcomes and measures: Risk scores were calculated based on available factors in each of these cohorts. Area under the receiver operating characteristic curve (AUC) was calculated to measure the performance of each risk score. Multiple imputation was used to assess whether missing data may have affected estimates for dementia risk. Results: Among the 6107 participants in 3 validation cohorts included for this study, 2184 participants without dementia at baseline were available from MAP (mean [SD] age, 80.0 [7.6] years; 1606 [73.5%] female), 548 participants without dementia at baseline were available from HRS-ADAMS (mean [SD] age, 79.5 [6.3] years; 288 [52.5%] female), and 3375 participants without dementia at baseline were available from CHS-CS (mean [SD] age, 74.8 [4.9] years; 1994 [59.1%] female). In all 3 cohorts, a similar AUC for dementia was obtained using CogDrisk, ANU-ADRI, and modified LIBRA (MAP cohort: CogDrisk AUC, 0.65 [95% CI, 0.61-0.69]; ANU-ADRI AUC, 0.65 [95% CI, 0.61-0.69]; modified LIBRA AUC, 0.65 [95% CI, 0.61-0.69]; HRS-ADAMS cohort: CogDrisk AUC, 0.75 [95% CI, 0.71-0.79]; ANU-ADRI AUC, 0.74 [95% CI, 0.70-0.78]; modified LIBRA AUC, 0.75 [95% CI, 0.71-0.79]; CHS-CS cohort: CogDrisk AUC, 0.70 [95% CI, 0.67-0.72]; ANU-ADRI AUC, 0.69 [95% CI, 0.66-0.72]; modified LIBRA AUC, 0.70 [95% CI, 0.68-0.73]). The CAIDE and LIBRA also provided similar but lower AUCs than the 3 aforementioned tools (eg, MAP cohort: CAIDE AUC, 0.50 [95% CI, 0.46-0.54]; LIBRA AUC, 0.53 [95% CI, 0.48-0.57]). The performance of CogDrisk-AD and ANU-ADRI in estimating AD risks was also similar. Conclusions and relevance: CogDrisk and CogDrisk-AD performed similarly to ANU-ADRI in estimating dementia and AD risks. These results suggest that CogDrisk and CogDrisk-AD, with a greater range of modifiable risk factors compared with other risk tools in this study, may be more informative for risk reduction.

Quantification of race/ethnicity representation in Alzheimer's disease neuroimaging research in the USA: a systematic review.

BACKGROUND: Racial and ethnic minoritized groups are disproportionately at risk for Alzheimer's Disease (AD), but are not sufficiently recruited in AD neuroimaging research in the United States. This is important as sample composition impacts generalizability of findings, biomarker cutoffs, and treatment effects. No studies have quantified the breadth of race/ethnicity representation in the AD literature. METHODS: This review identified median race/ethnicity composition of AD neuroimaging US-based research samples available as free full-text articles on PubMed. Two types of published studies were analyzed: studies that directly report race/ethnicity data (i.e., direct studies), and studies that do not report race/ethnicity but used data from a cohort study/database that does report this information (i.e., indirect studies). RESULTS: Direct studies (n = 719) have median representation of 88.9% white or 87.4% Non-Hispanic white, 7.3% Black/African American, and 3.4% Hispanic/Latino ethnicity, with 0% Asian American, Native Hawaiian/Pacific Islander, and American Indian/Alaska Native, Multiracial, and Other Race participants. Cohort studies/databases (n = 44) from which indirect studies (n = 1745) derived are more diverse, with median representation of 84.2% white, 83.7% Non-Hispanic white, 11.6% Black/African American, 4.7% Hispanic/Latino, and 1.75% Asian American participants. Notably, 94% of indirect studies derive from just 10 cohort studies/databases. Comparisons of two time periods using a median split for publication year, 1994-2017 and 2018-2022, indicate that sample diversity has improved recently, particularly for Black/African American participants (3.39% from 1994-2017 and 8.29% from 2018-2022). CONCLUSIONS: There is still underrepresentation of all minoritized groups relative to Census data, especially for Hispanic/Latino and Asian American individuals. The AD neuroimaging literature will benefit from increased representative recruitment of ethnic/racial minorities. More transparent reporting of race/ethnicity data is needed.

Members of some racial and ethnic minority groups in the USA are more likely to develop Alzheimer's Disease than white people. However, they are often not included in research studies of Alzheimer's Disease. We looked at the race/ethnicity composition of people evaluated in papers published describing Alzheimer's Disease research studies based in the USA that used images of the brain. We found that all racial/ethnic minority groups were underrepresented in Alzheimer's Disease research studies, especially Hispanic/Latino and Asian American individuals. It is important that studies include representatives of all populations both for the health of those populations and improved understanding of Alzheimer's Disease in all people. Such studies should also improve efforts to understand and address racial/ethnic disparities in Alzheimer's Disease diagnosis and treatment.

Mild Cognitive Impairment is Associated with Poorer Everyday Decision Making.

BACKGROUND: Older adults are faced with many unique and highly consequential decisions such as those related to finances, healthcare, and everyday functioning (e.g., driving cessation). Given the significant impact of these decisions on independence, wellbeing, and safety, an understanding of how cognitive impairment may impact decision making in older age is important. OBJECTIVE: To examine the impact of mild cognitive impairment (MCI) on responses to a modified version of the Short Portable Assessment of Capacity for Everyday Decision making (SPACED). METHODS: Participants were community-dwelling, actively driving older adults (N = 301; M age = 77.1 years, SD = 5.1; 69.4% with a college degree or higher; 51.2% female; 95.3% White) enrolled in the Advancing Understanding of Transportation Options (AUTO) study. A generalized linear model adjusted for age, education, sex, randomization group, cognitive assessment method, and study site was used to examine the relationship between MCI status and decision making. RESULTS: MCI status was associated with poorer decision making; participants with MCI missed an average of 2.17 times more points on the SPACED than those without MCI (adjusted mean ratio: 2.17, 95% CI: 1.02, 4.61, p = 0.044). CONCLUSION: This finding supports the idea that older adults with MCI exhibit poorer decision-making abilities than cognitively normal older adults. It also suggests that older adults with MCI may exhibit poorer decision making across a wide range of decision contexts.

Late-life depressive symptoms and white matter structural integrity within older Black adults.

Introduction: Older Black adults experience a high burden of depressive symptoms and cerebrovascular disease but the specific neurobiological substrates underlying the association between late-life depressive symptoms and brain integrity are understudied, particularly in within-group designs. Methods: Using the Center for Epidemiologic Studies Depression Scale and diffusion-tensor imaging, within-Black variation in the association between late-life depressive symptoms and white matter structural integrity was examined in 297 older Black participants without dementia that were enrolled across three epidemiological studies of aging and dementia. Linear regression models were used to test associations with DTI metrics (fractional anisotropy, trace of the diffusion tensor) as the outcomes and depressive symptoms as the predictor, while adjusting for age, sex, education, scanner, serotonin-reuptake inhibitor use, total volume of white-matter hyperintensities normalized by intracranial volume, and presence of white-matter hyperintensities at the voxel level. Results: Higher level of self-reported late-life depressive symptoms was associated with greater diffusion-tensor trace (reduced white matter integrity) in connections between commissural pathways and contralateral prefrontal regions (superior and middle frontal/dorsolateral prefrontal cortex), association pathways connecting dorsolateral prefrontal cortex with insular, striatal and thalamic regions, and association pathways connecting the parietal, temporal and occipital lobes and the thalamus. Discussion: This study demonstrated a discernable pattern of compromised white matter structural integrity underlying late-life depressive symptoms within older Black adults.

The Cognitive Correlates of Financial Literacy in Older Adults.

OBJECTIVES: This study examined the cognitive correlates of financial literacy using a comprehensive neuropsychological battery, and whether education modifies the relationship between cognition and financial literacy. METHODS: Sixty-six participants completed sociodemographic questionnaires, an assessment of financial literacy, and a neuropsychological assessment. Multiple linear regression models that controlled for age, sex, and education examined the main effects of cognitive measures that showed a significant bivariate association with financial literacy. RESULTS: After correcting for multiple comparisons, the Crystallized Composite score (p = .002) and the Picture Vocabulary test (p = .002) from the NIH Toolbox, and the Multilingual Naming Test (p > .001) from the Uniform Data Set 3 were associated with financial literacy. Contrary to our hypothesis, education did not interact with cognitive measures when considering financial literacy scores. CONCLUSIONS: Findings suggest that vocabulary knowledge and semantic memory may play an important role in financial literacy in older age. CLINICAL IMPLICATIONS: Assessing vocabulary knowledge and semantic processes may help to identify older adults with lower financial literacy skills. Additionally, financial literacy interventions may consider targeting individuals with lower vocabulary knowledge and semantic processing skills.

The small HDL particle hypothesis of Alzheimer's disease.

We propose the hypothesis that small high-density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. Concentrations of small HDLs in cerebrospinal fluid (CSF) and plasma were measured in 180 individuals ≥60 years of age using ion mobility methodology. Small HDL concentrations in CSF were positively associated with performance in three domains of cognitive function independent of apolipoprotein E (APOE) ε4 status, age, sex, and years of education. Moreover, there was a significant correlation between levels of small HDLs in CSF and plasma. Further studies will be aimed at determining whether specific components of small HDL exchange across the blood, brain, and CSF barriers, and developing approaches to exploit small HDLs for therapeutic purposes.

Interpersonal dysfunction predicts subsequent financial exploitation vulnerability in a sample of adults over 50: a prospective observational study.

OBJECTIVES: The goal of this study was to test whether interpersonal dysfunction, characterized by loneliness and/or dissatisfaction with relationships, is an imminent predictor of financial exploitation vulnerability (FEV) among adults age 50+ within a 6-month observation period. This study also tests whether FEV prospectively predicts interpersonal dysfunction. METHODS: Twenty-six adults aged 50 or older completed a study involving baseline data collection and 13 follow-ups over 6 months. Linear mixed models were used for primary analyses. RESULTS: After adjustment for demographic, psychological and cognitive covariates, there were between-person effects of FEV and interpersonal dysfunction across follow-ups, suggesting that those with generally higher interpersonal dysfunction compared to other participants also reported greater FEV (B(SE) = 1.09(.33), p = .003). There was a within-person effect (B(SE) = .08(.03), p = .007) of elevated interpersonal dysfunction predicting greater FEV two weeks later across all follow-ups. Within-person effect of FEV was not predictive of interpersonal dysfunction (B(SE) = .25(.15), p = .10). There was also a significant effect of age (B(SE) = -.06(.02), p = .007), such that older individuals had lower FEV throughout follow-ups. CONCLUSION: Among adults age 50+, individuals with higher interpersonal dysfunction relative to others in the study reported greater FEV throughout the 6-month observation period. Increased loneliness and social dissatisfaction, relative to one's average level, predicts subsequent increases in FEV, and may be an imminent risk factor for exploitation.

Rapid olfactory decline during aging predicts dementia and GMV loss in AD brain regions.

INTRODUCTION: Longitudinal multivariable analyses are needed to determine if the rate of olfactory decline during normal cognition predicts subsequent Alzheimer's disease (AD) diagnoses and brain dysmorphology. METHODS: Older adults (n = 515) were assessed annually for odor identification, cognitive function and dementia clinical diagnosis (max follow-up 18 years). Regional gray matter volumes (GMV) were quantified (3T MRI) in a cross-sectional subsample (n = 121). Regression models were adjusted for APOE-ε4 genotype, dementia risk factors and demographics. RESULTS: Faster olfactory decline during periods of normal cognition predicted higher incidence of subsequent MCI or dementia (OR 1.89, 95% CI: 1.26, 2.90, p < 0.01; comparable to carrying an APOE-ε4 allele) and smaller GMV in AD and olfactory regions (ß = -0.11, 95% CI -0.21, -0.00). DISCUSSION: Rapid olfactory decline during normal cognition, using repeated olfactory measurement, predicted subsequent cognitive impairment, dementia, and smaller GMVs, highlighting its potential as a simple biomarker for early AD detection. HIGHLIGHTS: Rate of olfactory decline was calculated from olfactory testing over ≥3 time points. Rapid olfactory decline predicted impaired cognition and higher risk of dementia. Neurodegeneration on 3T magnetic resonance imaging was identical in those with olfactory decline and Alzheimer's disease.