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

Introduction: White matter hypointensities (WMHs) are associated with cognitive decline and dementia. However, it remains unknown how race, ethnicity, and depression influence WMHs. This study examined the interactive effects of race/ethnicity and depression on WMHs and cognition.

Methods: Data from the National Alzheimer's Coordinating Center included 2411 older adults (773 Whites with and 1360 Whites without depression and 89 Blacks with and 189 Blacks without depression). Linear regressions assessed WMH differences across race/ethnicity and depression groups and the associations between WMH burden and cognition.

Results: Black older adults with depression showed greater global and regional WMH burden than Black older adults without depression, and depression significantly influenced the relationship between WMHs and cognitive impairment. Similar results were observed for Hispanic older adults; however, these findings were not observed in White older adults.

Discussion: These findings suggest that race and depression may jointly influence cerebrovascular disease burden as well as its associations with cognition in aging and dementia.

Alzheimer's disease manifests differently across ancestral groups, with African populations showing distinct fluid biomarker levels, neuroimaging patterns, and post mortem pathology. These differences may compromise diagnostic accuracy and exacerbate health disparities. This systematic review, examined studies published from 2015 to 2025 assessing amyloid-β and tau via fluid assays and neuroimaging. Findings reveal ancestry-linked variation where African populations exhibit lower cerebrospinal fluid/plasma Aβ42/Aβ40 and p-tau181 ratios, with neuroimaging showing broadly similar reduced positron emission tomography patterns but slightly elevated amyloid and reduced tau signals. Limited post mortem data suggest reduced plaque and tangle densities despite comparable dementia severity. Genetic, environmental, and sociocultural factors contribute to these disparities. Diagnostic thresholds derived from non-African cohorts risk underdiagnosing AD in African individuals. There is an urgent need to recalibrate and validate biomarker protocols to ensure equitable and accurate dementia diagnosis across diverse populations.

Introduction: Cardiorespiratory fitness (CRF) is linked to dementia risk, but moderating factors remain unclear. This study examined how and when CRF in adulthood is associated with late-onset dementia (> 65 years) and whether sex, civil status, or education moderate this association.

Methods: In a cohort of 370,980 dementia-free individuals followed for a mean of 11.9 (standard deviation 6.0) years, CRF was estimated via a submaximal cycle test, with dementia incidence obtained from Swedish National Healthcare Registries.

Results: Results showed that high CRF was associated with lower dementia risk in those under age 55 (hazard ratio [HR]: 0.58, 95% confidence interval [CI] 0.36-0.92) and those > 55 (HR: 0.75, 95% CI 0.63-0.89) at CRF assessment. Medium education levels moderate the association in individuals < 55 years.

Discussion: These findings underscore the role of maintaining a high CRF in dementia prevention, emphasizing education level as a critical moderating factor.

Highlights: High cardiorespiratory fitness (CRF) is longitudinally associated with a lower risk of late-onset dementia.The association was evident in those both under and over age 55 at CRF assessment.Higher education levels moderated the relationship in those < 55 years.Sex and civil status did not moderate the association.

Introduction: Establishing interchangeability between blood biomarkers and amyloid-positron emission tomography (PET) could help identify patients who would benefit from novel amyloid-targeting therapies for Alzheimer's disease.

Methods: Adult participants from the Global Alzheimer's Platform Foundation's Bio-Hermes study with clinical diagnosis of mild cognitive impairment/mild dementia and available amyloid-PET evaluations and Aβ42/40-based PrecivityAD^® (by C2N Diagnostics) and/or phosphorylated tau at threonine 217 (p-Tau217 (research use Meso Scale Discovery, Lilly) were included. Interchangeability between plasma-based tests (per pre-established thresholds) and amyloid-PET stratifications was evaluated.

Results: PrecivityAD (N = 537) and p-Tau217 (N = 531) plasma-based tests had high agreement with florbetapir-PET (overall percent agreement: 80.7% and 90.1%, respectively) and accurately selected patients identified as florbetapir-PET-positive (positive predictive value: 86.0% and 88.0%, respectively). Further, they were non-inferior to quantitative florbetapir-PET (at 37 Centiloids) for identifying positive florbetapir-PET visual reads.

Discussion: Results support the hypothesis that blood biomarkers may be interchangeable with amyloid-PET criteria for selecting patients who may benefit from treatment with novel amyloid-targeting therapies.

Highlights: Interchangeability of plasma-based tests and amyloid-PET stratifications was demonstrated.Non-inferiority of plasma-based biomarkers to amyloid-PET for identifying patients with AD pathology was observed.High agreement between plasma-based test stratification and florbetapir-PET expert visual read was observed.

Background: Biomarkers and Alzheimer's disease (AD) risk disclosure may help reduce disparities in dementia diagnosis and care in Indigenous communities.

Methods: Semi-structured interviews assessed beliefs about the causes of dementia, and interest in and perceived benefits and risks of obtaining AD risk information, including biomarkers.

Results: Thirty-two Indigenous and 26 non-Hispanic White individuals participated in the study. The Indigenous cohort endorsed divergent beliefs about the causes of dementia relative to the non-Hispanic White cohort. Eighty-one percent of the Indigenous cohort and 100% of the non-Hispanic White cohort endorsed interest in learning their AD risk primarily to improve health behaviors, gain health knowledge, and engage in treatments or clinical trials. Indigenous participants more frequently endorsed concerns about burdening family and limited access to health care.

Discussion: Incorporating discussions about causes of dementia, caregiver burden, and family involvement into return-of-results procedures may support informed, collective decision making.

Introduction: This study aimed to compare the willingness to use Alzheimer's disease (AD) predictive-diagnostic procedures between Mapuche (Indigenous) and non-Indigenous older adults in Chile.

Methods: We conducted a cross-sectional study including Mapuche (n = 167) and non-Indigenous (n = 248) older adults. Willingness to undergo five predictive-diagnostic procedures (AD risk test, neuropsychological assessment, blood test, brain imaging, and cerebrospinal fluid analysis) was evaluated. Logistic regression models were used to identify factors associated with willingness.

Results: Overall willingness was high, except for cerebrospinal fluid testing (39.1%). In fully adjusted models, Mapuche participants were significantly less willing to undergo neuropsychological assessment (77.8% vs. 92.3%), blood testing (68.3% vs. 89.9%), and brain imaging (73.1% vs. 84.3%). Key determinants of willingness varied by ethnic group and included age, sex, AD-related worry, social determinants, and number of dementia risk factors.

Discussion: Despite high overall willingness, ethnic identity and psychosocial factors significantly influenced receptiveness to AD predictive-diagnostic procedures.

Highlights: Indigenous populations in high-income countries face a higher risk of dementia, making Alzheimer's disease (AD) biomarker and diagnostic research a critical priority in these groups.Despite this, Indigenous and Latin American populations remain among the most underrepresented in dementia research.In a sample of Indigenous (Mapuche) and non-Indigenous older adults in Chile, most participants reported willingness to use AD biomarkers and diagnostic procedures.In fully adjusted models, Mapuche individuals were significantly less willing to undergo neuropsychological testing, blood tests, and brain imaging for AD risk prediction.Willingness to use AD biomarkers varied by ethnic identity and was influenced by age, social determinants, and attitudes toward AD.

Introduction: We examine how non-expert humans (young adults unfamiliar with dementia) and large language models (LLMs) perceive dementia in transcribed texts-recognizing signs that may indicate cognitive decline. Human perception is important, as it is often the driver for seeking medical evaluation. LLM perception is equally interesting given their potential as screening tools.

Methods: Humans and LLMs intuitively judged whether transcribed picture descriptions came from dementia patients or healthy controls. We represented texts using high-level, expert-guided features and used logistic regression to model perceptions and analyze coefficients.

Results: Human judgments are inconsistent, relying on a narrow and sometimes misleading set of cues. LLMs use a richer, more clinically aligned feature set. Both groups show a tendency toward false negatives.

Discussion: This work highlights the need to educate humans and LLMs to recognize a broader range of dementia-related linguistic signals. It also underscores the value of interpretability in dementia research.

Highlights: Explainable artificial intelligence (AI) uncovers linguistic cues that humans and large language models (LLMs) associate with dementia.LLMs allow scalable extraction of expert-defined features on picture descriptions.LLMs use broader cues than humans to detect dementia and better align with diagnoses.Humans and LLMs exhibit false negatives; LLMs view fluency as cognitive health.Understanding non-expert perceptions can guide education and improve early awareness.

Foundation models (FMs) are entering Alzheimer's disease and related dementias (ADRD), yet bedside impact remains limited. We analyze the interpretability and reliability gaps that impede adoption, including opaque inference, hallucinations in generative models, and weak causal grounding. We argue for hybrid artificial intelligence (AI) that pairs statistical learning with computable clinical knowledge and clinician oversight. We propose a three-level framework for hybrid AI integration: (1) knowledge retrieval with linked citations; (2) contextualized decision support that combines predictive models with actionable plans derived from expert rules; and (3) adaptive optimization through continuous feedback. We demonstrate the potential of hybrid AI using clinical examples, including individual-specific interpretation of novel biomarkers, integration of multimodal data including speech and text, as well as patient-centered digital therapeutics. Finally, we outline pragmatic evaluation aligned with reporting standards, prioritizing adoption, safety, equity, workload, and patient outcomes. This roadmap aims to convert benchmark gains into accountable, interpretable tools for ADRD care.

Highlights: Map artificial intelligence (AI) applications across clinical fields and reveal key findings in current literature.Identify how AI supports and advances next-generation technologies in dementia care.Present real-world cases where AI assists clinicians in context-specific scenarios.Examine major challenges and future opportunities in clinical AI adoption.

Introduction: The relationship between biological sex, considered a risk factor for Alzheimer's disease (AD), and bilingualism, a resilience factor, is unclear. We assessed this relationship in 335 individuals with mild cognitive impairment (MCI) in a Canadian cohort.

Methods: We used univariate analysis and structural equation modelling to study the relationship between female sex and bilingualism. We created a resilience index (RI) for each participant using the residual approach. Logistic and linear regressions predicted cognitive and brain health in relation to RI.

Results: Overall, bilingual males had increased RI. Higher RI was associated with less risk of AD and less neuropathology and glial activation as indexed by plasma p-tau181, neurofilament light, and glial fibrillary acidic protein.

Discussion: In MCI, the combination of elevated estradiol levels due to aromatization and bilingualism may provide synergistic protection for verbal memory, making old bilingual males more resilient.

Highlights: Sex steroids influence verbal memoryIn a structural equation modeling (SEM) model, verbal memory mediates cognitive declineElevated estradiol from aromatization makes old bilinguals more resilient.

Introduction: Overlaps in symptom presentation limits the capacity to predict functional impairment and future care needs in younger-onset dementia syndromes.

Methods: A general additive model (GAM) was applied to cross-sectional retrospective data from 375 participants with younger-onset dementia; 152 behavioral-variant frontotemporal dementia (bvFTD), 118 Alzheimer's disease (AD), 66 semantic dementia, and 39 progressive nonfluent aphasia (PNFA). This GAM aimed to explore the dynamic interrelationships between established measures of global cognition, apathy, and functional impairment.

Results: Our GAM significantly predicted functional impairment in all syndromes with a high explained variance (59.5%). Cognition and apathy emerged as significant predictors of functional impairment in each syndrome (p-values < .015). These relationships were consistently linear in AD, non-linear in SD, and mixed in bvFTD and PNFA (i.e., cognition linear and apathy non-linear).

Discussion: Our study shows the potential prognostic utility of GAMs for identifying syndrome-specific transition periods across group-level staging's of functional impairment.

Highlights: First study to apply a general additive model to functional impairment in younger-onset dementia.Studied 375 individuals with younger-onset Alzheimer's disease or frontotemporal dementia.Apathy and cognition were significant predictors of functional impairment in all syndromes.This modeling has significant implications for syndrome-specific prognosis and management.