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

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.

Introduction: Psychosis in Alzheimer's disease (AD) is associated with worse outcomes, yet no established biomarkers exist for early diagnosis and intervention. We compared tau positron emission tomography (PET) burden across older individuals with and without psychotic symptoms.

Methods: [18F]AV1451 tau PET binding was compared between 32 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects with psychotic symptoms (delusions and/or hallucinations) and 32 ADNI subjects without psychotic symptoms, matched for age, sex, race/ethnicity, and clinical severity. Tau was assessed in a priori regions of interest (ROIs) and in voxelwise analyses, both corrected for amyloid PET burden.

Results: Tau was greater in individuals with psychotic symptoms in the amygdala, hippocampus, frontal cortex, and early, middle, and late Braak stage regions in primary analyses. When considering subgroups, tau binding was greatest in those with concurrent delusions.

Discussion: Greater than expected tau burden for age, clinical severity, and amyloid burden may be relevant for psychotic symptoms in older adults.

Highlights: Tau positron emission tomography (PET) was elevated in individuals with psychosisElevated tau was independent of Alzheimer's disease (AD) clinical severity and amyloid burdenThere was variability in the regional distribution depending on psychosis type.

Introduction: The rising prevalence of Alzheimer's disease and related dementias (ADRD) poses major public health concerns. Public knowledge about ADRD diverges from scientific consensus, and consequently, public stigma presents barriers to diagnosis and care.

Method: This study addresses ADRD stigma in the United States using the well-established vignette approach. A stratified quota sample of 1115 adults matching national demographics were randomly assigned to one of six vignettes. Symptoms of the vignette character mirrored the presentation of ADRD and were reviewed by geriatric neuropsychologists for accuracy.

Results: Apart from small vignette effects, stigma was shaped by respondent characteristics. Higher stigma was predicted by less knowledge, being male, non-White race, and living in counties with higher ADRD prevalence. Surprisingly, personal contact showed no effect.

Discussion: Rehumanizing individuals with ADRD and enhancing ADRD knowledge should be public health priorities. Stigma reduction efforts need to address informational deficits and narratives that perpetuate negative perceptions.

Introduction: Culturally appropriate scales are needed to efficiently assess stigma among Arabic-speaking communities. This study aimed to validate the Arabic version of the Dementia Diagnosis Attitude Scale (A-DDAS).

Methods: The translated A-DDAS underwent pre-testing with native speakers in Australia. The final version of the scale was tested with Arabic-speaking adults aged ≥ 18 residing in Australia. The sample (N = 266) was randomly split such that one half (n = 133) underwent exploratory factor analysis and the other half (n = 133) underwent confirmatory factor analysis. Internal consistency reliability was assessed via Cronbach α.

Results: The final 10-item scale consisted of two factors with five items each: "fear of labelling" (α = 0.88) and "fear of discrimination" (α = 0.85), with inter-factor correlation r = 0.51 and high reliability (α = 0.87).

Discussion: The A-DDAS yielded good validity and reliability scores, confirming its suitability for use with Arabic-speaking Australians in stigma studies, educational interventions, and clinical settings.

Introduction: Early detection of mild cognitive impairment (MCI) is critical for intervention and dementia prevention. Interpretable linguistic features may offer transparent, cross-linguistic markers yet remain underexplored in bilingual dataset contexts.

Methods: Using the TAUKADIAL Challenge dataset, which includes English and Chinese picture descriptions, we extracted 93 language-specific linguistic features with the Efficient Linguistic Feature Extraction for Natural Language Datasets (ELFEN) package and 141 language-agnostic linguistic features using the Comprehensive Handcrafted Linguistic Features (LFTK) toolkit. One-way ANOVA and Tukey's Honestly Significant Difference tests assessed associations with diagnosis, task, and language.

Results: Seven ELFEN and 33 LFTK features showed significant differences between diagnostic groups. MCI speech exhibited reduced lexical diversity, fewer pronouns, greater use of numerals and participles, and longer sentences across both languages. Task- and language-based analyses revealed structural and lexical variability, with greater variability in Chinese responses.

Discussion: These findings identify statistically significant, interpretable linguistic features associated with MCI, establishing a cross-linguistic foundation for developing transparent, multilingual tools for early cognitive assessment.

Highlights: Nintey-three language-specific and 141 language-agnostic features are analyzed from bilingual speech.Seven ELFEN and 33 LFTK features were identified as significantly linked to MCI diagnosis.MCI speakers used fewer pronouns, showed lower lexical diversity, and produced longer sentences.Findings reveal consistent cross-linguistic markers in English and Chinese picture descriptions.The study offers an interpretable, statistically validated foundation for multilingual MCI screening tools.

Introduction: In Alzheimer's disease (AD) and vascular dementia (VaD), comorbidities shape disease trajectories and care needs, yet their timing across the lifespan remains poorly understood.

Methods: We analyzed comorbidities using in-patient hospital International Classification of Diseases 10th Revision codes in 10,730 UK Biobank participants with AD or VaD, spanning 20 years before to 10 years after diagnosis. Logistic regression and Bayesian network analysis identified time- and subtype-specific risk patterns, validated against controls.

Results: Distinct comorbidities emerged decades before diagnosis. In AD, depressive episodes, osteoporosis, and type 1 diabetes appeared up to 20 years pre-diagnosis, while VaD was characterized by early cerebral infarctions, type 1 diabetes, intestinal disorders, and rheumatoid arthritis, absent in controls.

Discussion: Although restricted to severe populations captured in in-patient data, excluding primary care, these findings reveal time-dependent prodromal patterns in AD and VaD, highlighting opportunities for targeted screening, prevention, and early intervention.

Hearing and vision loss are considered independent modifiable risk factors for dementia; however, the impact of their dual impairment is not clear and is crucial for preventive strategies. We performed a systematic review and meta-analysis until July 23, 2024, to assess the association of dual sensory impairment (DSI) and dementia. Pooled hazard ratios (HRs) were calculated using random-effects models. Heterogeneity was assessed through subgroup analysis and meta-regression. Population attributable fractions (PAFs) for DSI were calculated. We included 11 studies. DSI was associated with a 52% increased hazard of developing all-cause dementia. Alzheimer's disease (AD) and vascular dementia subtypes showed larger HRs. Heterogeneity was only high for AD. Meta-regressions showed non-significant associations. Overall PAF for DSI was 2.77%. DSI significantly increases the risk of dementia among adults. Comprehensive sensory assessments and interventions targeting both hearing and vision impairments are essential for effective dementia prevention strategies.

Highlights: Dual sensory impairment (hearing and vision) increases dementia risk by 52%.Population attributable fraction of dual sensory impairment for dementia is 2.77%.Sensory assessments are crucial for dementia prevention strategies.

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.