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

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.

Introduction: The incidence of Alzheimer's disease (AD) in Down syndrome (DS) exceeds 90%. Approximately 50% of people with DS have congenital heart disease (CHD). Having CHD increases risk for early-onset AD in populations without DS, but it is unclear if CHD influences AD in DS.

Methods: Data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) were used. Participants with CHD (n = 82, mean age = 39.9 ± 8.5 years, 97.6% White race) were age- and sex-matched to participants without CHD (n = 82, mean age = 40.5 ± 8.1 years, 98.8% White race). Cognitive assessments and Centiloid load (CL) (positron emission tomography) were compared by CHD status.

Results: People with CHD scored lower for visuospatial ability (β = -3.515, p = 0.022) but had higher CL (29.8 ± 12.8 vs. 39.8 ± 12.8, β = 8.00, p = 0.036) and were projected to hit Aβ positivity at a younger age (37.6 and 42.1 years).

Discussion: Presence of CHD may influence AD progression in DS.

Highlights: In adults with Down syndrome (DS), those with congenital heart disease (CHD) had higher amyloid beta and reached the threshold for an amyloid positivity at a younger age than those without CHDNo differences in cognition were seen in the age- and sex-matched sample based on CHD status; however, the average age of the sample may be too young to see cognitive changesCHDs may influence the timing of Alzheimer's disease (AD) in adults with DS.

Introduction: Lecanemab is a monoclonal antibody targeting amyloid plaques that has been approved for the treatment of early symptomatic Alzheimer's disease. Here, we report on the clinical history and outcomes of the first 70 patients at the University of Utah to receive amyloid-removal therapy.

Methods: This is a retrospective analysis of patients treated with lecanemab over a 26-month period. We extracted patient data from charts and analyzed demographics, health history, and clinical details with outcomes on lecanemab treatment.

Results: In total, we observed 14 cases (20%) of amyloid-related imaging abnormalities (ARIAs), which was significantly associated with apolipoprotein E ε4 homozygosity. Zero cases of ARIAs were symptomatic, and there was no association between distance from clinic and adverse effects.

Discussion: Our study examined the safety and tolerability of centrally managed lecanemab administration across a widely distributed region and suggests that use of distributed infusion sites increases access to disease-modifying treatment without significant increase in risk.

Highlights: Lecanemab therapy can be safely administered to patients across a broadly distributed area through a single clinical center.In our first 70 treated patients, 14 developed amyloid-related imaging abnormalities (ARIAs)-a rate of 20%, which is consistent with clinical trials of lecanemab.No patients experienced symptomatic ARIAs.ARIA incidence was significantly associated with apolipoprotein E genotype, but not other demographic factors, comorbid conditions, or baseline clinical details.

Introduction: Factors underlying discordant visual and quantitative amyloid beta-positron emission tomography (Aβ-PET) results and their clinical implications are not well understood.

Methods: Participants from the 1Florida Alzheimer's Disease Research Center (1FLADRC) underwent Aβ-PET, blood draw, brain magnetic resonance imaging (MRI), and neuropsychological testing. We evaluated differences in demographics, apolipoprotein E (APOE) status, biomarkers, and cognition among older adults with concordant and discordant visual-quantitative Aβ-PET. Discordance was defined as positive visual read (V) of Aβ-PET with below-threshold Centiloid quantification (Q; CL <25; V+/Q-) or negative visual read with CL ≥25 (V-/Q+).

Results: We studied 386 participants (mean age ± SD: 70.7 ± 7.8, 55.2% female, 44.6% Hispanic White). Compared to V+/Q-, V-/Q+ had a higher frequency of APOE ε4 carriers (40%). Black/African American participants were overrepresented in V-/Q+ (40.9%). Both discordant groups had higher plasma phosphorylated tau 217 (p-tau217) and glial fibrillary acidic protein (GFAP) than V-/Q- but lower than V+/Q+. Discordant groups had greater gray matter volume and better cognitive performance than V+/Q+.

Discussion: Discordant Aβ-PET findings likely hold clinical significance and may reflect early stages of neuropathological progression.

Highlights: Groups with concordant/discordant visual-quantitative amyloid beta-positron emission tomography (Aβ-PET) results were compared.Visual-/quant+ were more likely than visual+/quant- to be apolipoprotein E (APOE) ε4 carriers and Black/African American.Discordant groups had higher plasma phosphorylated tau 217 (p-tau217) and glial fibrillary acidic protein (GFAP) than concordant negative.Discordant groups had less atrophy and better cognition than concordant positive.Centiloid quantification should supplement visual reads in clinical settings.