Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring最新文献

Introduction: Evidence suggests that autonomic symptoms in frontotemporal dementia (FTD) may relate to hypothalamic pathology. We investigated (1) autonomic symptoms in FTD, primary psychiatric disorders (PPD), and controls; (2) hypothalamic volumes; and (3) their associations.

Methods: Autonomic Symptoms Questionnaire (ASQ) data were collected from FTD (n = 31), PPD (n = 30), and controls (n = 30). MRI data from these and additional participants (FTD n = 259, PPD n = 44, controls n = 62) were analyzed using a deep learning approach.

Results: FTD and PPD groups reported more cardiovascular symptoms than controls (p = 0.020; p = 0.049). FTD patients showed greater thermodysregulation (vs. PPD p = 0.026; vs. controls p = 0.012) and altered pain perception (FTD 13%, PPD 2%, controls 1%; p < 0.001). FTD showed smaller hypothalamic subregions, except the left inferior-tubular area. In FTD, autonomic symptoms correlated with subregional hypothalamic volumes.

Discussion: FTD patients exhibit increased autonomic symptoms across several domains compared to PPD and controls; moreover, FTD is associated with smaller regional hypothalamic volume.

Introduction: This study examined whether performance on the web-based Latin American Spanish Face-Name Associative Memory Exam (LAS-FNAME), an associative memory test, is associated with plasma biomarkers in autosomal dominant Alzheimer's disease (ADAD).

Methods: One hundred sixty-one members from the Colombian kindred with presenilin-1 (PSEN1) E280A mutation (61 cognitively unimpaired carriers, 22 cognitively impaired carriers, and 78 non-carriers), completed the web-based LAS-FNAME and provided blood samples for biomarker analysis. Analysis of covariance was used to compare LAS-FNAME performance among groups and Spearman correlations to examine its associations with levels of plasma phosphorylated tau (p-tau)217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP).

Results: Carriers had lower LAS-FNAME performance (P < 0.001) and higher p-tau217 (P < 0.001), NfL (P = 0.013), and GFAP (P < 0.001) levels than non-carriers. Higher p-tau217, NfL, and GFAP were associated with worse LAS-FNAME performance, controlling for age, sex, and education.

Discussion: The web-based LAS-FNAME is a promising tool for detecting early memory decline in AD, warranting future studies to evaluate its longitudinal utility.

Highlights: The web-based Latin American Spanish Face-Name Associative Memory Exam (LAS-FNAME) detects memory decline in presenilin 1 (PSEN1) mutation carriers.LAS-FNAME scores correlate with blood biomarkers in PSEN1 carriers.The web-based format enables remote assessment via participants' personal devices.The study was conducted in Spanish-speaking adults at risk for dementia.Findings support combined use of digital cognitive tools and blood biomarkers.

Introduction: We examined whether bilingualism was associated with a cognitive advantage among older urban- or rural-dwelling Mexican adults.

Methods: Participants were from the Mexican Health and Aging Study Ancillary Study on Cognitive Aging (Mex-Cog) from urban (N = 1063, 12% Spanish-English bilingual adults) and rural (N = 814, 19% Spanish-Indigenous bilingual adults) areas. Memory, language, and executive functioning were assessed. Weighted linear models stratified by locality evaluated effects of bilingualism on cognitive domains, adjusting for sociodemographic factors.

Results: In urban settings, Spanish-English bilingualism was not associated with cognition in any domain (all Ps > 0.05). In rural settings, Spanish-Indigenous bilingual adults had lower scores across all domains (Ps < 0.01).

Discussion: There was no evidence of a cognitive advantage among older bilingual adults in Mexico. Indigenous bilingual adults performed worse cognitively compared to Spanish-monolingual peers. Further work is needed to understand the linguistic and sociocultural characterization of older Mexican adults to better evaluate bilingualism and cognitive aging.

Introduction: Lecanemab, an anti-amyloid-beta antibody, is approved in over 40 countries. Patient demographic data exist for the US but are limited elsewhere. This study examined early real-world lecanemab use in Japan.

Methods: Using claims data from 18 municipalities, we identified patients prescribed lecanemab between December 2023 and September 2024. The study outcome was the discontinuation rate, with discontinuation defined as a ≥42-day prescription gap. Covariates included age, sex, long-term care certification, municipality size, comorbidities, Mini-Mental State Examination (MMSE) score, and Clinical Dementia Rating (CDR).

Results: We identified 123 lecanemab recipients (median age: 76 years, interquartile range: 73-79 years; women: 73.2%). Most had mild impairment: 60.9% with MMSE ≥24 and 79.3% with CDR 0.5. The discontinuation rate was 1.04/100 person-months, with most occurring within 1.5 months.

Discussion: In this first Asian report, lecanemab was mainly prescribed to older women with milder cognitive impairment. Early discontinuation may reflect cautious adoption in Japan.

For people living with Parkinson's disease (PD), cognitive impairment is a salient concern. The cumulative risk of mild cognitive impairment and dementia increases as the disease progresses, which contributes to loss of functional independence and increased institutionalization at late stages of PD. Yet, due to scarcity of time and resources, cognition is often an overlooked topic in busy neurology clinics. There are few opportunities for cognitive evaluation during clinical consults, and where it does occur, assessment methods are varied and unstandardized. Diagnostic and post-diagnostic care pathways for cognitive decline vary across clinical services, leaving people with PD falling through the resonant cracks of our healthcare systems. This perspective article highlights current gaps and inconsistencies in the diagnosis, evaluation, and management of cognitive disorders in PD. In doing so, we explore ways in which some of these issues may be rectified through best practice guidelines and critically analyze those that are more difficult to address.

Introduction: Neuropsychiatric symptoms and changes in everyday functioning emerge early in Alzheimer's disease, but the relationships among these signs are rarely considered. We aimed to examine associations between neuropsychiatric symptoms and daily functioning in cognitively unimpaired older adults.

Methods: 178 participants (70.4 ± 6.1 years; 62% female) and their study partners completed the Mild Behavioral Impairment Checklist (MBI-C) and Alzheimer's Disease Cooperative Study Activities of Daily Living Prevention Instrument (ADCS ADL-PI). We investigated associations between self- and study partner-reported MBI-C and ADCS ADL-PI.

Results: Higher study partner-reported MBI-C scores were associated with lower participant-reported (estimate [B] = -0.51, 95% confidence interval [CI] [-0.68, -0.34]) and study partner-reported (B = -0.50, 95% CI [-0.66, -0.34]) ADCS ADL-PI scores. Similar associations were apparent between participant-reported MBI-C and participant- and study partner-reported ADCS ADL-PI.

Discussion: Neuropsychiatric symptoms relate to daily functioning in cognitively unimpaired older adults. Early detection and management of these symptoms may improve the quality of life and sensitivity of clinical trial outcomes.

Highlights: Neuropsychiatric symptoms relate to worse daily function in unimpaired older adults.Difficulties with motivation and emotional regulation were the strongest predictors.Associations were seen with both self-reported and study partner-reported measures.

Introduction: Variables predicting Alzheimer's disease (AD) are not limited to individual-level risk factors. The purpose of this investigation is to assess multilevel predictors of AD prevalence.

Methods: US county-level datasets incorporating 45 predictor variables were analyzed cross-sectionally using artificial intelligence analytical methods. A Light Gradient-Boosting Machine model was trained to predict county-level AD after which model performance and feature importance were evaluated.

Results: The final model retained 20 features and explained 75% (R ² = 0.75) of the variance in AD prevalence. Racial and ethnic minority status showed the highest importance value (0.848), far exceeding all other features (e.g., poor sleep ranked second with importance value of 0.153).

Discussion: This study confirmed upstream factors as being significant predictors of AD prevalence and racial and ethnic minority status as being the most important. From a policy perspective, efforts to reduce population levels of AD prevalence should consider addressing racial and ethnic disparities.

Introduction: Human immunodeficiency virus (HIV) therapies now support survival into advanced ages by suppressing HIV replication and preserving immune function. Alzheimer's disease (AD), the most common neurologic degenerative condition, may now be treated with anti-amyloid therapies (AAT). HIV was an exclusionary criterion in clinical trials for AAT, leaving the safety and efficacy of these medications unknown in this setting.

Methods: We report the development of AD supported by careful evaluations and biomarkers over a 10-year period in a person living with well-controlled HIV infection.

Results: AD was diagnosed with consistent clinical and biomarker evidence. AAT was successfully administered without complications. HIV therapy remained effective.

Discussion: This report provides early evidence that AAT can be safely administered without detrimental effects on HIV therapy. The rapidly enlarging elderly HIV population will include an increasing number of individuals with AD who may benefit from this knowledge.

Introduction: Electroencephalography (EEG) provides a temporally precise index of neural dysfunction, capturing changes in oscillatory activity, connectivity, and network organization. While spectral slowing is well documented in Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), less is known about how these alterations extend to large-scale networks.

Methods: We studied 173 participants: 56 AD, 59 FTD, 26 DLB, and 32 healthy controls (HC). Resting-state EEG was analyzed to quantify spectral power and amplitude-envelope correlation-based connectivity across frequency bands.

Results: AD showed canonical slowing with delta/theta increases and posterior alpha loss. FTD exhibited preserved alpha but frontal beta reductions, while DLB displayed delta/theta excess, posterior alpha attenuation, and uniquely reduced gamma. Connectivity analyses revealed syndrome-specific patterns of network reorganization with distinct frequency-dependent signatures.

Discussion: EEG network metrics capture distinct disease signatures and may inform mechanistic models of dementia.

Background: Blood-based biomarkers offer a less invasive and more scalable alternative to cerebrospinal fluid (CSF) analysis and amyloid-positron emission tomography (PET) for the biological diagnosis of Alzheimer's disease (AD). Among blood-based biomarkers (BBMs), plasma phosphorylated tau217 (p-tau217) has shown the highest accuracy, although intermediate ("gray zone") values remain challenging to interpret.

Methods: In this study, 401 individuals across the Alzheimer's Disease (AD) continuum (Subjective Cognitive Decline, Mild Cognitive Impairment, and AD dementia) underwent clinical and biomarker assessment. Plasma p-tau217, p-tau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured. Core1 status was defined through CSF or amyloid-PET.

Results: Plasma p-tau217 demonstrated the strongest discrimination of Core1 positivity (area under the curve [AUC] = 0.95) and showed the steepest increase with disease progression. A two-cutoff strategy improved diagnostic accuracy (94%), though 18% of patients fell into the gray zone. Within this subgroup, p-tau181 was the only predictor of Core1 status and correctly reclassified 77.4% of indeterminate cases.

Discussion: These findings support a sequential plasma biomarkers approach for reliable AD detection.