Longitudinal decline in semantic versus letter fluency, but not their ratio, marks incident Alzheimer's disease in Latinx Spanish-speaking older individuals.

OBJECTIVE: To compare longitudinal verbal fluency performance among Latinx Spanish speakers who develop Alzheimer's disease to those who do not develop dementia in absolute number of words produced on each task and their ratio to combine both scores. METHOD: Participants included 833 Latinx Spanish-speaking older adults from a community-based prospective cohort in Manhattan. We performed growth curve modeling to investigate the trajectories of letter and semantic fluency, and their ratio (i.e., 'semantic index'), between individuals who developed Alzheimer's disease and those who did not (i.e., controls). The semantic index quantifies the proportion of words generated for semantic fluency in relation to the total verbal fluency performance. RESULTS: Letter fluency performance did not decline in controls; we observed a linear decline in those who developed Alzheimer's disease. Semantic fluency declined in both groups and showed an increased rate of change over time in the incident Alzheimer's disease group; in comparison, the control group had a linear and slower decline. There were no group differences in the longitudinal trajectory (intercept and slope) of the semantic index. CONCLUSION: A decline in letter fluency and a more rapid and accelerating decline over time in semantic fluency distinguished people who developed Alzheimer's disease from controls. Using the semantic index was not a superior marker of incident Alzheimer's disease compared to examining the two fluency scores individually. Results suggest the differential decline in verbal fluency tasks, when evaluated appropriately, may be useful for early identification of Alzheimer's disease in Latinx Spanish speakers, a historically understudied population.

Extrapyramidal signs and Alzheimer's disease prognosis in a multiethnic, community-based sample of demented elders.

INTRODUCTION: Extrapyramidal signs (EPS) are a common feature of Alzheimer's disease associated with worse outcomes in observational studies of dementia. Less research has been conducted on ethnic minority and non-clinic-based populations. METHODS: One hundred and forty-two multiethnic community-dwelling participants with dementia were selected. Adjusted Cox models were fitted for mortality, cognitive (Mini Mental State Examination ≤10), functional (Blessed Dementia Rating Scale ≥10), and dependency (needs full-time care) endpoints with baseline EPS as predictor. RESULTS: Thirty-seven participants (26.06%) had EPS at baseline. EPS predicted more rapid time to death (hazard ratio [HR] = 2.76, 95% confidence interval [CI] = 1.49, 5.42), and functional endpoint (HR = 3.88, 95% CI = 1.75, 8.62) but not cognitive and dependency endpoints. No evidence of interaction by ethnicity, age, sex, education, or apolipoprotein E ε4 polymorphism was found. DISCUSSION: Our results partially confirm previous studies on predominantly White, clinic-based samples. Further research is needed to better understand the etiological role of EPS in AD.

Costs During the Last Five Years of Life for Patients with Clinical and Pathological Confirmed Diagnosis of Lewy Body Dementia and Alzheimer's Disease.

BACKGROUND: Little is known regarding healthcare expenditures for patients with dementia with Lewy bodies (DLB) during the end of life. OBJECTIVE: This study estimated Medicare expenditures during the last 5 years of life in a decedent sample of patients who were clinically diagnosed with Alzheimer's disease (AD) or DLB and had autopsy confirmed diagnosis. METHODS: The study included 58 participants clinically diagnosed with mild dementia at study entry (AD: n = 44, DLB: n = 14) and also had autopsy-confirmed diagnoses of pure AD (n = 32), mixed AD+Lewy body (LB) (n = 5), or pure LB (n = 11). Total Medicare expenditures were compared by clinical and pathology confirmed diagnosis, adjusting for sex, age at death, and patient's cognition, function, comorbidities, and psychiatric and extrapyramidal symptoms. RESULTS: When pathology diagnoses were not considered, predicted annualized total Medicare expenditures during the last 5 years of life were similar between clinically diagnosed AD ($7,465±1,098) and DLB ($7,783±1,803). When clinical diagnoses were not considered, predicted expenditures were substantially higher in patients with pathology confirmed mixed AD+LB ($12,005±2,455) than either pure AD ($6,173±941) or pure LB ($4,629±1,968) cases. Considering clinical and pathology diagnosis together, expenditures for patients with clinical DLB and pathology mixed AD+LB ($23,592±3,679) dwarfed other groups. CONCLUSION: Medicare expenditures during the last 5 years of life were substantially higher in patients with mixed AD+LB pathology compared to those with pure-AD and pure-LB pathologies, particularly in those clinically diagnosed with DLB. Results highlight the importance of having both clinical and pathology diagnoses in examining healthcare costs.

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.

Clinical Trajectories at the End of Life in Autopsy-Confirmed Dementia Patients With Alzheimer Disease and Lewy Bodies Pathologies.

BACKGROUND AND OBJECTIVES: Evaluating and understanding the heterogeneity in dementia course has important implications for clinical practice, health care decision-making, and research. However, inconsistent findings have been reported with regard to the disease courses of the 2 most common dementias: Alzheimer disease (AD) and dementia with Lewy bodies (DLB). Using autopsy-confirmed diagnoses, we aimed to examine the disease trajectories in the years before death among patients with dementia with pure AD, pure DLB, or mixed (AD and DLB) pathologies. METHODS: The current retrospective longitudinal study included 62 participants with autopsy-confirmed diagnoses of pure AD (n = 34), mixed AD and DLB (AD + DLB; n = 17), or pure DLB (n = 11) from the Predictors 2 Cohort Study, a prospective, clinic-based, cohort of patients with dementia. Generalized estimating equation models, with time zero at death, were used to examine the trajectory of cognition (Folstein Mini-Mental State Examination [MMSE]), function (activities of daily living [ADL]), and Dependence Scale among patients with different autopsy-confirmed diagnosis (pure AD, AD + DLB, and pure DLB). The models were adjusted for age, sex, education, and baseline features including extrapyramidal signs, MMSE, ADL, and Dependence Scale. RESULTS: The participants on average received 9.4 ± 4.6 assessments at 6-month intervals during a mean 5.4 ± 2.9 years of follow-up. The 3 groups were similar in both cognition and function status at baseline. Cognition and function were highly correlated among patients with AD + DLB but not in pure AD or pure DLB at baseline. Patients of the 3 groups all declined in both cognition and function but had different trajectories of decline. More specifically, the patients with pure DLB experienced approximately double the rate of both cognitive decline and functional decline than the patients with pure AD, and the mixed pathology group showed double the rate of functional decline as compared to pure AD. DISCUSSION: In this longitudinal study, we found that among patients with dementia, those with Lewy body pathology experienced faster cognitive and functional decline than those with pure AD pathology.

Neuropsychological Predictors of Severe Functional Dependency in a Multiethnic Community Cohort of Individuals with Alzheimer's Disease.

To assess the predictive value of neuropsychological tests for severe dependency in Alzheimer's disease as defined by the Equivalent Institutional Care Rating Scale, in a multiethnic, community cohort. The sample included 146 elders from the Predictors 3 cohort. Cox proportional hazard models tested the predictive value of each neuropsychological test at baseline on relative risk of meeting severe dependency. Higher semantic processing and memory test scores at baseline were associated with lower risk of meeting severe dependency in the adjusted Cox models. The integrity of semantic processing and memory abilities in dementia appears to predict time to severe functional dependency.