Confronting Alzheimer's Disease Risk in Women: A Feasibility Study of Memory Screening as Part of the Annual Gynecological Well-Woman Visit.

Objective: Routine health care visits offer the opportunity to screen older adults for symptoms of Alzheimer's disease (AD). Many women see their gynecologist as their primary health care provider. Given this unique relationship, the Women's Preventive Services Initiative and the American College of Obstetrics and Gynecology advocate for integrated care of women at all ages. It is well-established that women are at increased risk for AD, and memory screening of older women should be paramount in this effort. Research is needed to determine the feasibility and value of memory screening among older women at the well-woman visit. Materials and Methods: Women aged 60 and above completed a 5-item subjective memory screener at their well-woman visit at the Columbia University Integrated Women's Health Program. Women who endorsed any item were considered to have a positive screen and were given the option to pursue clinical evaluation. Rates of positive screens, item endorsement, and referral preferences were examined. Results: Of the 530 women approached, 521 agreed to complete the screener. Of those, 17.5% (n = 91) were classified as positive. The most frequently endorsed item was difficulty with memory or thinking compared with others the same age. Among women with positive screens, 57.5% were interested in pursuing clinical referrals to a memory specialist. Conclusion: Results support the feasibility and potential value of including subjective memory screening as part of a comprehensive well-woman program. Early identification of memory loss will enable investigation into the cause of memory symptoms and longitudinal monitoring of cognitive change.

Baseline Depressive Symptoms as a Predictor of Incident Dementia in a Prospectively Followed Cohort of Elders with Essential Tremor.

BACKGROUND: Essential tremor (ET) patients may exhibit a variety of non-motor features, including cognitive decline and depressive symptoms. Studies of several neurodegenerative diseases link depression to cognitive decline, suggesting depression is an early marker of dementia. We examined whether baseline depressive symptoms predict incident dementia in elders with ET. METHODS: 141 ET cases age 70 or older at baseline, enrolled in a prospective study of cognitive performance, took part in evaluations at baseline, and at 18, 36, 54, and 72 months. Participants completed the Geriatric Depression Scale (GDS), a 30-item self-report measure of depressive symptoms, and a battery of neuropsychological tests and functional assessments, from which we derived cognitive diagnoses at each evaluation. We calculated Cox proportional hazards regression equations to determine incident dementia risk based on participants' baseline depression scores. RESULTS: Mean baseline age was 81.5 + 6.7 years. Higher baseline GDS scores were associated with increased risk of dementia in an unadjusted model (hazards ratio [HR] = 1.11, 95% confidence interval [CI] = 1.02 - 1.20, p = 0.01), and after controlling for baseline age, education, number of medications, and tremor onset age (HR = 1.13, 95% CI = 1.02 - 1.25, p = 0.02). CONCLUSION: Baseline depression scores predicted incident dementia in elders with ET. With each one-point increase in baseline depression score, there was a 13% increase in incident dementia risk. Given the published data that reported depression may be twice as high in elders with ET compared to controls,1 this association is particularly worrisome in the ET population.

Subjective Sleep Disturbance and Lewy Pathology: Data from a Cohort of Essential Tremor Brain Donors.

INTRODUCTION: Sleep disturbances have been associated with essential tremor (ET). However, their pathophysiological underpinnings remain unknown. In this exploratory study, we examined the association between subjective sleep disturbances and the presence of Lewy pathology (LP) on postmortem brain examination in ET cases. METHODS: Fifty-two ET cases enrolled in a prospective, longitudinal study were assessed over an average period of 42 months. Cases completed the Pittsburgh Sleep Quality Index (PSQI), which yields seven component scores (e.g., sleep quality, sleep latency). For each component score, we calculated the difference between the last score and the baseline score. Brains were harvested at death. Each had a complete neuropathological assessment, including extensive α-synuclein immunostaining. We examined the associations between baseline PSQI scores and the change in PSQI scores (last - first), and LP on postmortem brain examination. RESULTS: ET cases had a mean baseline age of 87.1 ± 4.8 years. LP was observed in 12 (23.1%) of 52 cases; in 7 of these 12, LP was observed in the locus coeruleus (LC). Change in time needed to fall asleep (last - first sleep latency component score) was associated with presence of LP on postmortem brain examination - greater increase in sleep latency was associated with higher odds of LP (odds ratio = 2.98, p = 0.02). The greatest increase in sleep latency was observed in cases with LP in the LC (p = 0.04). CONCLUSION: In ET cases, increases in sleep latency over time could be a marker of underlying LP, especially in the LC.

Summer of Translational Aging Research for Undergraduates (STAR U): Short-term outcomes of a training program to advance diversity in aging research.

Purpose: The Summer of Translational Aging Research for Undergraduates (STAR U) program, funded by the National Institute on Aging and the Alzheimer's Association, aims to advance diversity in aging research through undergraduate education. Here, we evaluate the effectiveness of the program in cultivating a diverse cohort of scientists from underrepresented backgrounds. Method: Forty-eight (96%) of 50 STAR U alumni completed a program evaluation survey between April and August 2023. The survey collected data on demographic characteristics of the alumni, educational/career goals, program experiences, and post-program outcomes, including information about continued education and scientific engagement. Results: Ninety-one percent of respondents indicated that STAR U was "extremely significant" or "very significant" in influencing them to pursue a career in science, and 93% found STAR U to be effective in influencing decisions to pursue a career in aging research specifically. Forty one percent of all respondents were already accepted or enrolled in science-related advanced degree programs, with half enrolled in doctoral degree programs. Of the students who were not enrolled in graduate school, 89% of respondents indicated they had plans to enroll in advanced degrees in the future. Respondents actively disseminated their research, with 10% of STAR U scholars reporting leading or co-authoring papers intended for publication in a peer-reviewed journal (10%). In fact, review of PubMed shows that to date, 22 students (44%) have a combined total of 44 publications in peer reviewed journals. Qualitative feedback underscored the program's impact on career exploration, as well as the impact of mentorship and the supportive environment provided by STAR U. Conclusions: The STAR U program shows promise as an impactful model for advancing diversity in the scientific workforce focused on aging research by strengthening scholars' goals for pursuing graduate education, careers in science, and research in aging in particular. Its individualized approach supports students in addressing challenges and fosters a supportive environment. STAR U serves as a catalyst for underrepresented students in STEM, showcasing the significance of tailored initiatives in promoting diversity and inclusion in aging research.

The Miami Framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology.

Increasing appreciation of the phenotypic and biological overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, alongside evolving biomarker evidence for a pre-symptomatic stage of disease and observations that this stage of disease might not always be clinically silent, is challenging traditional views of these disorders. These advances have highlighted the need to adapt ingrained notions of these clinical syndromes to include both the full phenotypic continuum - from clinically silent, to prodromal, to clinically manifest - and the expanded phenotypic spectrum that includes ALS, frontotemporal dementia and some movement disorders. The updated clinical paradigms should also align with our understanding of the biology of these disorders, reflected in measurable biomarkers. The Miami Framework, emerging from discussions at the Second International Pre-Symptomatic ALS Workshop in Miami (February 2023; a full list of attendees and their affiliations appears in the Supplementary Information) proposes a classification system built on: first, three parallel phenotypic axes - motor neuron, frontotemporal and extrapyramidal - rather than the unitary approach of combining all phenotypic elements into a single clinical entity; and second, biomarkers that reflect different aspects of the underlying pathology and biology of neurodegeneration. This framework decouples clinical syndromes from biomarker evidence of disease and builds on experiences from other neurodegenerative diseases to offer a unified approach to specifying the pleiotropic clinical manifestations of disease and describing the trajectory of emergent biomarkers.

Prevalence of and Annual Conversion Rates to Mild Cognitive Impairment and Dementia: Prospective, Longitudinal Study of an Essential Tremor Cohort.

OBJECTIVE: Despite recent attention to cognitive impairment in essential tremor, few studies examine rates of conversion to diagnoses of mild cognitive impairment and dementia. Development of dementia in essential tremor is associated with loss of functional ability and a doubling of mortality rate. This prospective, longitudinal study comprehensively reports the prevalence and incidence of, and the annual rates of conversion to, mild cognitive impairment and dementia in an essential tremor cohort. METHODS: Patients underwent detailed cognitive assessments and were assigned diagnoses of normal cognition, mild cognitive impairment, or dementia. There were 222 patients at baseline (mean age = 79.3 ± 9.7 years), and 177 patients participated in follow-up evaluations at 18, 36, 54, and 72 months (mean years of observation = 5.1 ± 1.7). Data were compared to those of historical controls and Parkinson disease patients. RESULTS: The cumulative prevalence of dementia and average annual conversion rate of mild cognitive impairment to dementia were 18.5% and 12.2%, nearly three times higher than rates in the general population, and approximately one half the magnitude of those reported for Parkinson disease patients. The cumulative prevalence of mild cognitive impairment (26.6%) was almost double that of the general population, but less than that in Parkinson disease populations. INTERPRETATION: We present the most complete exposition of the longitudinal trajectory of cognitive impairment in an essential tremor cohort yet presented. The prevalence of and conversion rates to dementia in essential tremor fall between those associated with the natural course of aging and the more pronounced rates observed in Parkinson disease. ANN NEUROL 2024;95:1193-1204.

Systemic inflammation in relation to exceptional memory in the Long Life Family Study (LLFS).

Background and objectives: We previously found a substantial familial aggregation of healthy aging phenotypes, including exceptional memory (EM) in long-lived persons. In the current study, we aim to assess whether long-lived families with EM and without EM (non-EM) differ in systemic inflammation status and trajectory. Methods: The current study included 4333 participants of the multi-center Long Life Family Study (LLFS). LLFS families were classified as EM (556 individuals from 28 families) or non-EM (3777 individuals from 416 families), with 2 or more offspring exhibiting exceptional memory performance (i.e. having baseline composite z-score representing immediate and delayed story memory being 1.5 SD above the mean in the nondemented offspring sample) considered as EM. Blood samples from baseline were used to measure inflammatory biomarkers including total white blood cell (WBC) and its subtypes (neutrophils, lymphocytes, monocytes) count, platelet count, high sensitivity C-reactive protein, and interleukin-6. Generalized linear models were used to examine cross-sectional differences in inflammatory biomarkers at baseline. In a sub-sample of 2227 participants (338 subjects from 24 EM families and 1889 from 328 non-EM families) with repeated measures of immune cell counts, we examined whether the rate of biomarker change differed between EM and non-EM families. All models were adjusted for family size, relatedness, age, sex, education, field center, APOE genotype, and body mass index. Results: LLFS participants from EM families had a marginally higher monocyte count at baseline (b = 0.028, SE = 0.0110, p = 0.010) after adjusting for age, sex, education, and field site, particularly in men (p < 0.0001) but not in women (p = 0.493) (p-interaction = 0.003). Over time, monocyte counts increased (p < 0.0001) in both EM and non-EM families, while lymphocytes and platelet counts decreased over time in the non-EM families (p < 0.0001) but not in the EM families. After adjusting for multiple variables, there was no significant difference in biomarker change over time between the EM and non-EM families. Discussion: Compared with non-EM families, EM families had significantly higher monocyte count at baseline but had similar change over time. Our study suggests that differences in monocyte counts may be a pathway through which EM emerges in some long-lived families, especially among men.

Whole genome-wide sequence analysis of long-lived families (Long-Life Family Study) identifies MTUS2 gene associated with late-onset Alzheimer's disease.

INTRODUCTION: Late-onset Alzheimer's disease (LOAD) has a strong genetic component. Participants in Long-Life Family Study (LLFS) exhibit delayed onset of dementia, offering a unique opportunity to investigate LOAD genetics. METHODS: We conducted a whole genome sequence analysis of 3475 LLFS members. Genetic associations were examined in six independent studies (N = 14,260) with a wide range of LOAD risk. Association analysis in a sub-sample of the LLFS cohort (N = 1739) evaluated the association of LOAD variants with beta amyloid (Aß) levels. RESULTS: We identified several single nucleotide polymorphisms (SNPs) in tight linkage disequilibrium within the MTUS2 gene associated with LOAD (rs73154407, p = 7.6 × 10-9). Association of MTUS2 variants with LOAD was observed in the five independent studies and was significantly stronger within high levels of Aß42/40 ratio compared to lower amyloid. DISCUSSION: MTUS2 encodes a microtubule associated protein implicated in the development and function of the nervous system, making it a plausible candidate to investigate LOAD biology. HIGHLIGHTS: Long-Life Family Study (LLFS) families may harbor late onset Alzheimer's dementia (LOAD) variants. LLFS whole genome sequence analysis identified MTUS2 gene variants associated with LOAD. The observed LLFS variants generalized to cohorts with wide range of LOAD risk. The association of MTUS2 with LOAD was stronger within high levels of beta amyloid. Our results provide evidence for MTUS2 gene as a novel LOAD candidate locus.

Sleep problems as predictors of cognitive decline in essential tremor: A prospective longitudinal cohort study.

BACKGROUND: There is growing evidence that essential tremor (ET) patients are at high risk of cognitive impairment. Predictors of cognitive impairment have not been studied extensively. There is evidence from cross-sectional studies that sleep dysregulation is associated with cognitive dysfunction in ET, but longitudinal studies of the impact of sleep disruption on cognitive change have not been conducted. We investigated the extent to which sleep problems predict cognitive change in patients with ET. METHODS: ET cases enrolled in a prospective, longitudinal study of cognitive performance. Sleep quality was assessed using the Pittsburg Sleep Quality Index (PSQI). Cognitive abilities across five domains (memory, executive function, attention, language, and visuospatial ability), and a global cognitive score (mean of the domains) were extracted from an extensive neuropsychological assessment. Generalized estimated equations were used to examine the association between baseline sleep problems and cognitive changes over three follow-up assessments each spaced 18 months apart. RESULTS: The 188 non-demented ET cases had a mean age of 77.7 ± 9.5 years. Longer sleep latency was associated with longitudinal decline in executive function (p = 0.038), and marginally with longitudinal decline in global cognitive performance (p = 0.075). After excluding 29 cases with mild cognitive impairment, results were similar. CONCLUSION: Cognitively healthy people with ET who have longer sleep latency had greater declines in executive function during prospective follow-up. Early detection of, and possibly intervention for, abnormal sleep latency may protect against certain aspects of cognitive decline in ET patients.

Changes in Digital Speech Measures in Asymptomatic Carriers of Pathogenic Variants Associated With Frontotemporal Degeneration.

BACKGROUND AND OBJECTIVES: Clinical trials developing therapeutics for frontotemporal degeneration (FTD) focus on pathogenic variant carriers at preclinical stages. Objective, quantitative clinical assessment tools are needed to track stability and delayed disease onset. Natural speech can serve as an accessible, cost-effective assessment tool. We aimed to identify early changes in the natural speech of FTD pathogenic variant carriers before they become symptomatic. METHODS: In this cohort study, speech samples of picture descriptions were collected longitudinally from healthy participants in observational studies at the University of Pennsylvania and Columbia University between 2007 and 2020. Participants were asymptomatic but at risk for familial FTD. Status as "carrier" or "noncarrier" was based on screening for known pathogenic variants in the participant's family. Thirty previously validated digital speech measures derived from automatic speech processing pipelines were selected a priori based on previous studies in patients with FTD and compared between asymptomatic carriers and noncarriers cross-sectionally and longitudinally. RESULTS: A total of 105 participants, all asymptomatic, included 41 carriers: 12 men [30%], mean age 43 ± 13 years; education, 16 ± 2 years; MMSE 29 ± 1; and 64 noncarriers: 27 men [42%]; mean age, 48 ± 14 years; education, 15 ± 3 years; MMSE 29 ± 1. We identified 4 speech measures that differed between carriers and noncarriers at baseline: mean speech segment duration (mean difference -0.28 seconds, 95% CI -0.55 to -0.02, p = 0.04); word frequency (mean difference 0.07, 95% CI 0.008-0.14, p = 0.03); word ambiguity (mean difference 0.02, 95% CI 0.0008-0.05, p = 0.04); and interjection count per 100 words (mean difference 0.33, 95% CI 0.07-0.59, p = 0.01). Three speech measures deteriorated over time in carriers only: particle count per 100 words per month (ß = -0.02, 95% CI -0.03 to -0.004, p = 0.009); total narrative production time in seconds per month (ß = -0.24, 95% CI -0.37 to -0.12, p < 0.001); and total number of words per month (ß = -0.48, 95% CI -0.78 to -0.19, p = 0.002) including in 3 carriers who later converted to symptomatic disease. DISCUSSION: Using automatic processing pipelines, we identified early changes in the natural speech of FTD pathogenic variant carriers in the presymptomatic stage. These findings highlight the potential utility of natural speech as a digital clinical outcome assessment tool in FTD, where objective and quantifiable measures for abnormal behavior and language are lacking.

Using digital assessment technology to detect neuropsychological problems in primary care settings.

Introduction: Screening for neurocognitive impairment and psychological distress in ambulatory primary and specialty care medical settings is an increasing necessity. The Core Cognitive Evaluation™ (CCE) is administered/scored using an iPad, requires approximately 8 min, assesses 3- word free recall and clock drawing to command and copy, asks questions about lifestyle and health, and queries for psychological distress. This information is linked with patients' self- reported concerns about memory and their cardiovascular risks. Methods: A total of 199 ambulatory patients were screened with the CCE as part of their routine medical care. The CCE provides several summary indices, and scores on 44 individual digital clock variables across command and copy tests conditions. Results: Subjective memory concerns were endorsed by 41% of participants. Approximately 31% of participants reported psychological distress involving loneliness, anxiety, or depression. Patients with self-reported memory concerns scored lower on a combined delay 3- word/ clock drawing index (p < 0.016), the total summary clock drawing command/ copy score (p < 0.050), and clock drawing to command Drawing Efficiency (p < 0.036) and Simple and Complex Motor (p < 0.029) indices. Patients treated for diabetes and atherosclerotic cardiovascular disease (ASCVD) scored lower on selected CCE outcome measures (p < 0.035). Factor analyses suggest that approximately 10 underlying variables can explain digital clock drawing performance. Discussion: The CCE is a powerful neurocognitive assessment tool that is sensitive to patient's subjective concerns about possible decline in memory, mood symptoms, possible cognitive impairment, and cardiovascular risk. iPad administration ensures total reliability for test administration and scoring. The CCE is easily deployable in outpatient ambulatory primary care settings.

Cognitive trajectories: exploring the predictive role of subjective cognitive decline and awareness of age-related changes for cognitive functioning.

Background: We investigated whether aspects of subjective cognitive aging, including awareness of age-related gains and losses in cognition (AARC-gains, AARC-losses) and subjective cognitive decline (SCD), predict change in objective cognitive function as measured by verbal reasoning (VR) and working memory (WM). Methods: We used longitudinal data for 3,299 cognitively healthy UK residents aged 65+. We used data on AARC and SCD assessed in 2019, and cognitive tasks assessed in 2019, 2020, and 2021. We used latent growth curve modeling, latent class growth analysis, and growth mixture modeling. Results: For VR, multiple growth trajectories were not evident. Mean VR at baseline was 37.45; this remained stable over time. Higher AARC-gains in cognition (mean intercept = -0.23; 95%CI: -0.31; -0.16), higher AARC-losses in cognition (mean intercept = -0.37; 95%CI: -0.46; -0.28), and lower SCD (mean intercept = 2.92; 95%CI: 2.58; 3.58) were associated with poorer VR at baseline. A three-class growth mixture model-class varying best represented trajectories of WM. In Class 1 (N = 182) mean WM at baseline was 31.20; this decreased by 2.48 points each year. In Class 2 (N = 119) mean WM at baseline was 23.12; this increased by 3.28 points each year. In Class 3 (N = 2,998) mean WM at baseline was 30.11; and it remained stable. Higher AARC-gains (Odds Ratio = 1.08; 95%CI: 1.03; 1.14) and AARC-losses (Odds Ratio = 1.10; 95%CI: 1.04; 1.16) in cognition predicted greater likelihood of being in Class 2 than Class 3. Conclusion: Although both higher AARC-gains and AARC-losses indicate poorer concurrent cognition, higher AARC-gains may be a resource that facilitates future cognitive improvement.

A prospective cohort study of familial versus sporadic essential tremor cases: Do clinical features evolve differently across time?

BACKGROUND: Although essential tremor (ET) is often divided into familial and sporadic cases, few data compare the evolution of clinical features in these groups over time. Leveraging data from a prospective, longitudinal study, we present analyses of the evolution of a broad range of cognitive, motor (i.e., tremor, tandem gait) and other features (e.g., disability) of ET. METHODS: Sixty-six familial and 23 sporadic ET cases completed in-home evaluations at baseline and 18, 36, and 54-month follow-ups. Assessments included detailed neuropsychological testing and videotaped neurological examinations. Analyses compared the longitudinal course of 16 clinical features in familial and sporadic cases. RESULTS: Baseline mean age was 75.2 ± 8.8 years and mean observation period was 4.7 ± 0.3 years. Tremor onset age was lower and childhood onset more common in familial than sporadic cases (p's = 0.02). Longitudinal analyses revealed no significant differences between clinical features displayed by familial and sporadic cases, or differences between the patterns of change in clinical features observed in these groups across time. Sporadic cases' daily activity skills declined significantly, whereas familial cases' did not, p's = 0.04 and 0.34, respectively; however, this finding was non-significant when controlling for false discovery rate. Several additional non-significant trends were noted. CONCLUSION: Familial and sporadic ET cases differed in onset age, and in the prevalence of childhood tremor onset. Although a number of interesting trends were observed, no significant differences in the evolution of clinical features over time in patients with and without a family history of ET were revealed.

Racial/Ethnic Disparities in Misidentification of Dementia in Medicare Claims: Results from the Washington Heights-Inwood Columbia Aging Project.

BACKGROUND: Misidentification of dementia in Medicare claims is quite common. OBJECTIVE: We examined potential race/ethnic disparities in misidentification of dementia in Medicare claims in a diverse cohort of older adults who underwent careful clinical assessment. METHODS: Participants were enrolled in the Washington Heights-Inwood Columbia Aging Project (WHICAP), a multiethnic, population-based, prospective study of cognitive aging in which dementia status was assessed using a rigorous clinical protocol. ICD-9-CM and ICD-10-CM diagnosis codes in all available Medicare claims (1999-2019) were compared to clinical dementia diagnosis and categorized into three mutually exclusive groups: 1) congruent-, 2) over-, and 3) under- identification during the study period. Multinomial logistic regression model was used to examine the relationship between race (White, African American/Black, other) and ethnicity (Hispanic/Latinx, non-Hispanic/Latinx) and congruency of dementia identification after controlling for clinical (cognition, function, comorbidities) and demographic characteristics (age, sex, education), and inpatient and outpatient utilization. RESULTS: Across all person-years, 88.4% had congruent identification of dementia compared to clinical diagnosis, in 4.1% of the times participants were over-identified with dementia, and 7.5% of the times the participants were under-identified. Rates of misidentification was higher in minority participants than in White, non-Hispanic participants. Multivariable estimation results showed that the probability of over-identification with dementia was 2.2% higher for African American/Black than White (p = 0.05) and 2.7% higher for Hispanic participants than non-Hispanics (p = 0.03) participants. Differences in under-identification by race/ethnicity were not statistically significant. CONCLUSIONS: African American/Black and Hispanic participants were more likely over-identified with dementia in Medicare claims.

Virtual Assessment as a Way to Reduce Help-seeking Barriers in Older Adults With Subjective Cognitive Decline.

Subjective cognitive decline (SCD), a potential early marker for neurodegenerative disease such as Alzheimer's disease, is common among older adults. Although it is often regarded as a personal health concern, most individuals with SCD do not seek help from a health care professional. Help-seeking (HS) is a complex, individualized process with significant life-course implications, and older adults often face several barriers to HS across personal, socioeconomic, and cultural domains. The pandemic exacerbated these barriers by imposing additional limitations on in-person care. In response, virtual assessment became a popular method to conduct remote care. We provide a narrative review of the challenges and triumphs that came with the transition from in-person, pen-paper cognitive assessments to virtual cognitive assessments. In addition, we address the impact virtual assessment had in tackling barriers that previously limited individuals with SCD from formal HS. We argue that virtual cognitive assessment helps alleviate health access barriers to HS (e.g., cost, transportation, and physician availability) and allows individuals with different coping styles to undergo assessment within more convenient environments. We hope the findings presented in this review inform health care practice, public education, and future research targeted towards the use of virtual assessment to facilitate HS in older adults with SCD.

Neuropsychiatric Symptoms and Trajectories of Dependence and Cognition in a Sample of Community-dwelling Older Adults with Dementia.

BACKGROUND AND OBJECTIVES: Neuropsychiatric symptoms (NPS), including psychotic symptoms (hallucinations, illusions, delusions), agitation/aggression, and depressed mood, are common in individuals with Alzheimer's disease (AD) and predict poorer outcomes, including faster disease progression. We aimed to evaluate associations between NPS and cognition and dependence in a multi-ethnic sample of community-dwelling older adults with AD. METHODS: Predictors 3 (P3) is a cohort study of AD disease courses recruiting older adults aged 65 and above residing in upper Manhattan. A total of 138 of 293 participants had probable AD at the study baseline. We fit linear mixed models to examine longitudinal associations of time-varying NPS (psychotic symptoms, agitation/aggression, and depressed mood) with dependence and cognition, adjusted for race-ethnicity, sex, education, age, clinical dementia rating score, APOE-ε4, and comorbidity burden; separate interaction models were fit for age, Hispanic ethnicity, and sex. RESULTS: Psychotic symptoms were associated with faster rates of increasing dependence and declining cognition over time, agitation/aggression with faster rates of declining cognition, and depressed mood with faster rates of increasing dependence. Among psychotic symptoms, delusions, but not hallucinations or illusions, were associated with worse outcome trajectories. Depressed mood predicted an accelerated increase in dependence in males but not females. CONCLUSION: Our results confirm and extend prior results in clinic-based samples. The presence of NPS was associated with worse trajectories of dependence and cognition in this muti-ethnic sample of older adults with AD. Importantly, sex modified the association between depressed mood and dependence. Our results on NPS as predictors of differential AD progression in a community-dwelling, ethnically diverse sample serve to better inform the clinical care of patients and the future development of AD therapies.

Education as a Moderator of Help Seeking Behavior in Subjective Cognitive Decline.

OBJECTIVE: Disparities in Alzheimer disease (AD) and differences in help seeking (HS) across sociodemographic groups warrant public health concern. Research addressing such disparities must shift toward the earliest clinical manifestations of AD to optimize diagnosis, intervention and care planning. Subjective cognitive decline (SCD), a risk state for AD, provides an important context in which to examine sociodemographic-related disparities in HS. PARTICIPANTS AND METHODS: One hundred sixty-seven cognitively healthy older adults (M age =73, M education =16) (26.4% Black, Asian, or "Other") completed SCD questionnaire, HS questions, and mood measures (depression and anxiety). Binary logistic adjusted regressions examined: (a) the association between SCD and HS; and (b) the extent to which education moderated the relationship between SCD and HS. SCD [b = 0.06, SE=0.13, P <0.001, odds ratio=1.06, 95% CI (1.03, 1.08)] and education [b=0.32, SE=0.09, P <0.001, odds ratio=1.37, 95% CI (1.15, 1.64)] were independently associated with HS, with significant interaction between education and SCD on HS [b=0.2, SE=0.01, P =0.01, odds ratio=1.02, 95% CI (1.00, 1.03)]. CONCLUSIONS: Findings elucidate the importance of tailoring SCD-related psychoeducational resources depending on educational background as a preliminary stepping-stone in encouraging HS among older adults who may be at particular risk for developing dementia.

Validation of a Multivariate Prediction Model of the Clinical Progression of Alzheimer's Disease in a Community-Dwelling Multiethnic Cohort.

BACKGROUND: The major aims of the three Predictors Studies have been to further our understanding of Alzheimer's disease (AD) progression sufficiently to predict the length of time from disease onset to major disease outcomes in individual patients with AD. OBJECTIVES: To validate a longitudinal Grade of Membership (L-GoM) prediction algorithm developed using clinic-based, mainly white patients from the Predictors 2 Study in a statistically representative community-based sample of Hispanic (N = 211) and non-Hispanic (N = 62) older adults (with 60 males and 213 females) from the Predictors 3 Study and extend the algorithm to mild cognitive impairment (MCI). METHODS: The L-GoM model was applied to data collected at the initial Predictors 3 visit for 150 subjects with AD and 123 with MCI. Participants were followed annually for up to seven years. Observed rates of survival and need for full-time care (FTC) were compared to those predicted by the algorithm. RESULTS: Initial MCI/AD severity in Predictors 3 was substantially higher than among clinic-based AD patients enrolled at the specialized Alzheimer's centers in Predictors 2. The observed survival and need for FTC followed the L-GoM model trajectories in individuals with MCI or AD, except for N = 32 subjects who were initially diagnosed with AD but reverted to a non-AD diagnosis on follow-up. CONCLUSION: These findings indicate that the L-GoM model is applicable to community-dwelling, multiethnic older adults with AD. They extend the use of the model to the prediction of outcomes for MCI. They also justify release of our L-GoM calculator at this time.

Association between cognitive diagnosis and a range of significant life events in an elderly essential tremor cohort: a longitudinal, prospective analysis.

Background: Although essential tremor (ET) patients have greater odds of mild cognitive impairment (MCI) and dementia than age-matched controls, the functional consequences of these enhanced odds are unknown. We examined associations between cognitive diagnosis and the occurrence of near falls, falls, use of a walking aid or a home health aide, non-independent living, or hospitalizations within a prospective, longitudinal study of ET patients. Methods: A total of 131 ET patients (mean baseline age = 76.4 ± 9.4 years) completed a battery of neuropsychological tests and questions about life events and were assigned diagnoses of normal cognition (NC), MCI, or dementia at the baseline and at 18-, 36-, and 54-month follow-ups. Kruskall-Wallis, chi-square, and Mantel-Haenszel tests assessed whether the diagnosis was associated with the occurrence of these life events. Results: Patients with final diagnoses of dementia were more often reported as living non-independently than NC or MCI patients and more often used walking aids than NC patients, with a p-value of <0.05. Patients with a final MCI or dementia diagnosis more often employed a home health aide than NC patients, with a p-value of <0.05. Moreover, Mantel-Haenzsel tests revealed linear associations between the occurrence of these outcomes and the level of cognitive impairment, with a p-value of <0.001 (i.e., dementia > MCI > NC). Conclusion: Cognitive diagnosis was associated with reported life events of ET patients, including the use of a mobility aid, employment of a home health aide, and removal from an independent living situation. These data provide rare insights into the important role cognitive decline plays in the experiences of ET patients.