BACKGROUND: Plasma biomarkers of Alzheimer\'s disease and related dementias predict global cognitive performance and decline over time; it remains unclear how they associate with changes in different dementia syndromes affecting distinct cognitive domains.
METHODS: In a prospective study with repeated assessments of a randomly selected population-based cohort (n = 787, median age 73), we evaluated performance and decline in different cognitive domains over up to 8 years in relation to plasma concentrations of amyloid beta 42/40 (Aβ42/40) ratio, phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP).
RESULTS: Cross-sectionally, memory showed the strongest associations with p-tau181, and attention, executive, and visuospatial functions with NfL. Longitudinally, memory decline was distinguishable with all biomarker profiles dichotomized according to data-driven cutoffs, most efficiently with Aβ42/40. GFAP and Aβ42/40 were the best discriminators of decline patterns in language and visuospatial functions, respectively.
CONCLUSIONS: These relatively non-invasive tests may be beneficial for clinical screening after replication in other populations and validation through neuroimaging or cerebrospinal fluid analysis.
CONCLUSIONS: We performed a prospective study with up to 8 years of repeated domain-specific cognitive assessments and baseline plasma Alzheimer\'s disease and related dementias biomarker measurements in a randomly selected population-based cohort. We considered distinct growth curves of trajectories of different cognitive domains and survival bias induced by missing data by adding quadratic time and applying joint modeling technique. Cross-sectionally, memory showed the strongest associations with plasma phosphorylated tau181, while attention, executive, and visuospatial functions were most strongly associated with neurofilament light chain. Longitudinally, memory and visuospatial declines were most efficiently distinguished by dichotomized amyloid beta 42/40 profile among all plasma biomarkers, while language was by dichotomized glial fibrillary acidic protein. These relatively non-invasive tests may be beneficial for clinical screening; however, they will need replication in other populations and validation through neuroimaging and/or cerebrospinal fluid assessments.

UNASSIGNED: We investigated cognitive profiles among diverse, middle-aged and older Hispanic/Latino adults in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) cohort using a cross-sectional observational study design.
UNASSIGNED: Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.6%), and 38.4% reported less than a high school education. We used latent profile analysis of demographically adjusted z scores on SOL-INCA neurocognitive tests spanning domains of verbal memory, language, processing speed, and executive function.
UNASSIGNED: Statistical fit assessment indices combined with clinical interpretation suggested five profiles: (1) a Higher Global group performing in the average-to-high-average range across all cognitive and instrumental activity of daily living (IADL) tests (13.8%); (2) a Higher Memory group with relatively high performance on memory tests but average performance across all other cognitive/IADL tests (24.6%); (3) a Lower Memory group with relatively low performance on memory tests but average performance across all other cognitive/IADL tests (32.8%); (4) a Lower Executive Function group with relatively low performance on executive function and processing speed tests but average-to-low-average performance across all other cognitive/IADL tests (16.6%); and (5) a Lower Global group performing low-average-to-mildly impaired across all cognitive/IADL tests (12.1%).
UNASSIGNED: Our results provide evidence of heterogeneity in the cognitive profiles of a representative, community-dwelling sample of diverse Hispanic/Latino adults. Our analyses yielded cognitive profiles that may assist efforts to better understand the early cognitive changes that may portend Alzheimer\'s disease and related dementias among diverse Hispanics/Latinos.
UNASSIGNED: The present study characterized cognitive profiles among diverse middle-aged and older Hispanic/Latino adults.Latent profile analysis of neurocognitive test scores was the primary analysis conducted.The target population consists of middle-aged and older Hispanic/Latino adults enrolled in the Hispanic Community Health Study/Study of Latinos and ancillary Study of Latinos - Investigation of Neurocognitive Aging.

BACKGROUND: Dementia risk may be elevated in socioeconomically disadvantaged neighborhoods. Reasons for this remain unclear, and this elevation has yet to be shown at a national population level.
METHODS: We tested whether dementia was more prevalent in disadvantaged neighborhoods across the New Zealand population (N = 1.41 million analytic sample) over a 20-year observation. We then tested whether premorbid dementia risk factors and MRI-measured brain-structure antecedents were more prevalent among midlife residents of disadvantaged neighborhoods in a population-representative NZ-birth-cohort (N = 938 analytic sample).
RESULTS: People residing in disadvantaged neighborhoods were at greater risk of dementia (HR per-quintile-disadvantage-increase = 1.09, 95% confidence interval [CI]:1.08-1.10) and, decades before clinical endpoints typically emerge, evidenced elevated dementia-risk scores (CAIDE, LIBRA, Lancet, ANU-ADRI, DunedinARB; β\'s 0.31-0.39) and displayed dementia-associated brain structural deficits and cognitive difficulties/decline.
CONCLUSIONS: Disadvantaged neighborhoods have more residents with dementia, and decades before dementia is diagnosed, residents have more dementia-risk factors and brain-structure antecedents. Whether or not neighborhoods causally influence risk, they may offer scalable opportunities for primary dementia prevention.

BACKGROUND: This study examined lucid episodes among people living with late-stage Alzheimer\'s disease and related dementias (PLWD) and then developed a typology of these episodes to help characterize them.
METHODS: Family caregivers of PLWD provided information about witnessed episodes, including proximity to death, cognitive status, duration, communication quality, and circumstances prior to lucid episodes on up to two episodes (caregiver N = 151; episode N = 279). Latent class analysis was used to classify and characterize empirically distinct clusters of lucid episodes.
RESULTS: Four lucid episode types were identified. The most common type occurred during visits with family and among PLWD who lived > 6 months after the episode. The least common type coincided with family visits and occurred within 7 days of the PLWD\'s death.
CONCLUSIONS: Findings suggest that multiple types of lucid episodes exist; not all signal impending death; and some, but not all, are precipitated by external stimuli.

BACKGROUND: Limited evidence exists on the associations of discontinuing versus continuing long-term opioid therapy (LTOT) with pain intensity, physical function, and depression among patients with Alzheimer\'s disease and related dementias (ADRD).
METHODS: A cohort study among 138,059 older residents with mild-to-moderate ADRD and receipt of LTOT was conducted using a 100% Medicare nursing home sample. Discontinuation of LTOT was defined as no opioid refills for ≥ 60 days. Outcomes were worsening pain, physical function, and depression from baseline to quarterly assessments during 1- and 2-year follow-ups.
RESULTS: The adjusted odds of worsening pain and depressive symptoms were 29% and 5% lower at the 1-year follow-up and 35% and 9% lower at the 2-year follow-up for residents who discontinued versus continued LTOT, with no difference in physical function.
CONCLUSIONS: Discontinuing LTOT was associated with lower short- and long-term worsening pain and depressive symptoms than continuing LTOT among older residents with ADRD.
CONCLUSIONS: Discontinuing long-term opioid therapy (LTOT) was associated with lower short- and long-term worsening pain. Discontinuing LTOT was related to lower short- and long-term worsening depression. Discontinuing LTOT was not associated with short- and long-term physical function.

UNASSIGNED: To examine the associations between neighborhood resources (i.e., number of restaurants, recreation centers, or social services for seniors and persons with disability per land area) and cognitive decline among a community-dwelling long-term care population and whether they differ by baseline cognition status.
UNASSIGNED: Prospective longitudinal cohort study.
UNASSIGNED: We used a longitudinal dataset that assessed over a two-year period older adults receiving state-funded home- and community-based services in Michigan Metropolitan areas (N = 9,802) and applied nonlinear mixed models with a random intercept with Poisson distribution.
UNASSIGNED: Cognitively intact older adults were less likely to experience cognitive decline when they resided in resource-rich neighborhoods, compared to those cognitively intact but living in neighborhoods that lacked resources. But their cognitively impaired or dementia-diagnosed counterparts did not similarly benefit from living in neighborhoods with rich resources.
UNASSIGNED: Neighborhood resources may be an important aspect of intervention to mitigate cognitive decline before older adults become cognitively impaired.

BACKGROUND: Cancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer\'s disease and related dementias (ADRD).
METHODS: In the UK Biobank, we investigated associations between cancer history and five structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed-effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution of MRI markers.
RESULTS: Cancer history was associated with smaller mean hippocampal volume (b = -19 mm3 , 95% CI = -36, -1) and lower mean cortical thickness in the Alzheimer\'s disease signature region (b = -0.004 mm, 95% CI = -0.007, -0.000). Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.
CONCLUSIONS: Some brain MRI markers associated with ADRD risk were elevated in adults with a history of cancer. The magnitude of the adverse associations varied across quantiles of neuroimaging markers, and the pattern suggests possible harmful associations for individuals already at high ADRD risk.
CONCLUSIONS: We found no evidence of an inverse association between cancer history and ADRD-related neurodegeneration. Cancer history was associated with smaller mean hippocampal volume and lower mean cortical thickness in the Alzheimer\'s disease signature region. Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.

The National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer\'s Disease and Alzheimer\'s Related Dementia Clinical Trials (IMPACT) Collaboratory convened a Lived Experience Panel (LEP) to inform the development of research priorities and provide input on conducting embedded pragmatic clinical trials (ePCTs) of dementia care interventions. Given the importance of people with lived experience to dementia research, and the unique considerations of engaging people with dementia, we report on our process for the recruitment, selection, and initial convening of the IMPACT LEP.
The IMPACT Engaging Partners Team, in partnership with the Alzheimer\'s Association, sought nominations of individuals with mild cognitive impairment or early-stage dementia, care partners of other people living with dementia (PLWD), and proxy representatives for individuals with mid-to-late stage dementia. The 11-member LEP was composed of individuals with diverse personal experiences in part due to their age, race, ethnicity, gender, sexual orientation, geography, disability, or type of dementia. In its first year, the LEP met with IMPACT\'s Patient and Caregiver Relevant Outcomes Core and Ethics and Regulation Core.
LEP members provided valuable insights and nuanced discussion of issues relevant to ePCTs in dementia care from a broad range of personal experience. Panelists identified key research priorities and provided insight on outcomes often studied by researchers. The LEP also informed investigators\' approaches to waivers and modifications of written informed consent and evaluation of minimal risk. Summary reports of the LEP meetings with each Core are available on the IMPACT website. At the end of the first year, changes were made to the composition of the LEP, and opportunities were identified for expanding panelist engagement with IMPACT investigators, as were priorities and scope for future input.
The IMPACT LEP provides a model for engaging PLWD and care partners in the research process as collaborators.

BACKGROUND: There is evidence that health care utilization increases after incident dementia, particularly after dementia diagnosis and toward the end of life; however, less is known about utilization in the years before dementia identification.
METHODS: In this retrospective cohort study we obtained data on n = 5547 beneficiaries from the Health and Retirement Study (HRS)-Medicare linked sample (n = 1241 with and n = 4306 without dementia) to compare longitudinal trends in health care costs and utilization in the 6 years preceding dementia identification relative to a confounder-balanced reference group without dementia.
RESULTS: We found that persons with dementia had a greater prevalence of outpatient emergency department (ED), inpatient hospital, skilled nursing, and home health use, and total health care costs in the years preceding dementia identification compared to their similar counterparts without dementia across a comparable timespan in later life.
CONCLUSIONS: This study provides evidence to suggest greater healthcare burden may exist well before clinical manifestation and identification of dementia.
CONCLUSIONS: Several studies have documented the tremendous healthcare-related costs of living with dementia, particularly toward the end of life. Dementia is a progressive neurodegenerative disease, which, for some, includes a prolonged pre-clinical phase. However, health services research to date has seldom considered the time before incident dementia. This study documents that health care utilization and costs are significantly elevated in the years before incident dementia relative to a demographically-similar comparison group without dementia.

Alzheimer\'s disease and related dementias (ADRD) present a looming public health crisis, affecting roughly 5 million people and 11 % of older adults in the United States. Despite nationwide efforts for timely diagnosis of patients with ADRD, >50 % of them are not diagnosed and unaware of their disease. To address this challenge, we developed ADscreen, an innovative speech-processing based ADRD screening algorithm for the protective identification of patients with ADRD. ADscreen consists of five major components: (i) noise reduction for reducing background noises from the audio-recorded patient speech, (ii) modeling the patient\'s ability in phonetic motor planning using acoustic parameters of the patient\'s voice, (iii) modeling the patient\'s ability in semantic and syntactic levels of language organization using linguistic parameters of the patient speech, (iv) extracting vocal and semantic psycholinguistic cues from the patient speech, and (v) building and evaluating the screening algorithm. To identify important speech parameters (features) associated with ADRD, we used the Joint Mutual Information Maximization (JMIM), an effective feature selection method for high dimensional, small sample size datasets. Modeling the relationship between speech parameters and the outcome variable (presence/absence of ADRD) was conducted using three different machine learning (ML) architectures with the capability of joining informative acoustic and linguistic with contextual word embedding vectors obtained from the DistilBERT (Bidirectional Encoder Representations from Transformers). We evaluated the performance of the ADscreen on an audio-recorded patients\' speech (verbal description) for the Cookie-Theft picture description task, which is publicly available in the dementia databank. The joint fusion of acoustic and linguistic parameters with contextual word embedding vectors of DistilBERT achieved F1-score = 84.64 (standard deviation [std] = ±3.58) and AUC-ROC = 92.53 (std = ±3.34) for training dataset, and F1-score = 89.55 and AUC-ROC = 93.89 for the test dataset. In summary, ADscreen has a strong potential to be integrated with clinical workflow to address the need for an ADRD screening tool so that patients with cognitive impairment can receive appropriate and timely care.