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

Training studies typically investigate the cumulative rather than the analytically challenging immediate effect of exercise on cognitive outcomes. We investigated the dynamic interplay between single-session exercise intensity and time-locked recognition speed-accuracy scores in older adults with Alzheimer's dementia (N = 17) undergoing a 24-week dual-task regime. We specified a state-of-the-art hierarchical Bayesian continuous-time dynamic model with fully connected state variables to analyze the bi-directional effects between physical and recognition scores over time. Higher physical performance was dynamically linked to improved recognition (-1.335, SD = 0.201, 95% Bayesian credible interval [BCI] [-1.725, -0.954]). The effect was short-term, lasting up to 5 days (-0.368, SD = 0.05, 95% BCI [-0.479, -0.266]). Clinical scores supported the validity of the model and observed temporal dynamics. Higher physical performance predicted improved recognition speed accuracy in a day-by-day manner, providing a proof-of-concept for the feasibility of linking exercise training and recognition in patients with Alzheimer's dementia.

Highlights: Hierarchical Bayesian continuous-time dynamic modeling approachA total of 72 repeated physical exercise (PP) and integrated recognition speed-accuracy (IRSA) measurementsPP is dynamically linked to session-to-session variability of IRSAHigher PP improved IRSA in subsequent sessions in subjects with Alzheimer's dementiaShort-term effect: lasting up to 4 days after training session.

Introduction: We examined the relationship between sedentary behavior (SB), moderate-to-vigorous physical activity (MVPA), and white matter hyperintensity (WMH) volumes, a common magnetic resonance imaging (MRI) marker associated with risk of neurodegenerative disease in middle-aged to older adults.

Methods: We used data from the UK Biobank (n = 14,415; 45 to 81 years) that included accelerometer-derived measures of SB and MVPA, and WMH volumes from MRI.

Results: Both MVPA and SB were associated with WMH volumes (β_MVPA = -0.03 [-0.04, -0.01], p < 0.001; β_SB = 0.02 [0.01, 0.03], p = 0.007). There was a significant interaction between SB and MVPA on WMH volumes (β_SB×MVPA = -0.015 [-0.028, -0.001], p _SB×MVPA = 0.03) where SB was positively associated with WMHs at low MVPA, and MVPA was negatively associated with WMHs at high SB.

Discussion: While this study cannot establish causality, the results highlight the potential importance of considering both MVPA and SB in strategies aimed at reducing the accumulation of WMH volumes in middle-aged to older adults.

Highlights: SB is associated with greater WMH volumes and MVPA is associated with lower WMH volumes.Relationships between SB and WMH are strongest at low levels of MVPA.Associations between MVPA and WMH are strongest at high levels of SB.Considering both SB and MVPA may be effective strategies for reducing WMHs.

Introduction: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD). There are no effective treatments targeting these symptoms.

Methods: To facilitate identification of causative mechanistic pathways, we initiated an effort (NIH: U01AG079850) to collate, harmonize, and analyze all available NPS data (≈ 100,000 samples) of diverse ancestries with whole-genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP).

Results: This study will generate a genomic resource for Alzheimer's disease with both harmonized whole-genome sequencing and NPS phenotype data that will be publicly available through NIAGADS. Primary analyses will (1) identify novel genetic risk factors associated with NPS in AD, (2) characterize the shared genetic architecture of NPS in AD and primary psychiatric disorders, and (3) assess the role of ancestry effects in the etiology of NPS in AD.

Discussion: Expansion of the ADSP to harmonize and refine NPS phenotypes coupled with the proposed core analyses will lay the foundation to disentangle the molecular mechanisms underlying these detrimental symptoms in AD in diverse populations.

Highlights: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD).There are no effective treatments targeting NPS in AD.The current effort aims to collate, harmonize, and analyze all NPS data from the Alzheimer's Disease Sequencing Project.Core analyses will identify underlying genetic factors and mechanistic pathways.The harmonized genomic and phenotypic data from this initiative will be available through National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site.

Introduction: We aimed to determine the effect of years of schooling (YoS) and age on the Mexican adaptation of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-MX) scores in preclinical carriers group (PCG) and non-carriers group (NCG) of the APP _V717I mutation.

Methods: We included 39 first-degree Mexican relatives of APP _V717I carriers (PCG = 15; NCG = 24). We report eight CERAD-MX tasks: Mini-Mental State Examination (MMSE), Word List Learning (WLL), Delayed Recall (WLD) and Recognition (WLR), Constructional Praxis Copy (CPC) and Recall (CPR), Semantic Verbal Fluency (SVF), and Verbal Boston Naming (VBN), comparing both groups' performance and simulating new samples' random vectors by inverse transform sampling.

Results: PCG and NCG performed similarly on CERAD-MX. In both groups, YoS and age influence all z scores. A positive age effect resulted for PCG on CPC and SVF; for the NCG on MMSE, SVF, and VBN.

Discussion: All tasks are influenced by YoS. Higher YoS/younger age or YoS/older age interactions affected different tasks, suggesting that YoS confounds outcomes.

Highlights: Years of schooling (YoS) and age affect the Mexican adaptation of the Consortium to Establish a Registry for Alzheimer's Disease scores of APP _V717I preclinical carriers.Preclinical carriers underperformed non-carriers on Constructional Praxis Recall.Fewer YoS emerges as a confounding variable when detecting cognitive failures.Younger participants in both groups overperformed the older ones in the Memory tasks.Randomized data simulation increases statistical power when analyzing rare diseases.

Introduction: Poorer baseline functioning is associated with long-term cognitive decline among Hispanic older adults, but little is known about associations of these factors with Alzheimer's disease (AD) neuroimaging biomarkers.

Methods: A total of 461 Hispanic and White non-Hispanic (NHW) older adults who are cognitively normal (n = 76), had impaired cognition without mild cognitive impairment (MCI) (n = 41), or carried a diagnosis of MCI (n = 253) or dementia (n = 91) completed neuropsychological and functional assessment, genetic testing, and brain magnetic resonance imaging (MRI). Structural equation modeling (SEM) was used to examine predictive associations between functional and cognitive measures of AD neuroimaging biomarkers.

Results: MRI volumes significantly predicted functional limitations in both groups. Sex and amyloid load significantly predicted functional limitations among the Hispanic group only. Years of education and MRI regional volume were the strongest predictors of cognition among both groups.

Discussion: Results indicate that functional performance is associated with early AD biomarkers among Hispanic older adults. Clinical implications are discussed.

Highlights: The current study addresses health disparities in Alzheimer's disease (AD) and related dementia assessment among Hispanics by identifying measures sensitive to early AD biomarkers.Associations of functional measures with AD genetic and neuroimaging biomarkers revealed that similarities in these associations exist between Hispanic and White non-Hispanic individuals, but biological sex and amyloid load significantly predicted functional limitations among the Hispanic group only.These results have clinical implications for physicians who treat Hispanic AD patients and indicate that when compared to traditional diagnostic assessments, functional assessments may better aid in AD diagnostic precision among Hispanics.

Introduction: We tested associations between two retinal measures (optic disc pallor, peripapillary retinal nerve fiber layer [pRNFL] thickness) and four magnetic resonance imaging markers of cerebral small vessel disease (SVD; lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces [ePVSs]).

Methods: We used PallorMetrics to quantify optic disc pallor from fundus photographs, and pRNFL thickness from optical coherence tomography scans. Linear and logistic regression assessed relationships between retinal measures and SVD markers. Participants (N = 108, mean age 51.6) were from the PREVENT Dementia study.

Results: Global optic disc pallor was linked to ePVSs in the basal ganglia in both left (β = 0.12, standard error [SE] = 0.05, P < 0.05) and right eyes (β = 0.13, SE = 0.05, P < 0.05). Associations were also noted in different disc sectors. No pRNFL associations with SVD markers were found.

Discussion: Optic disc pallor correlated with ePVSs in the basal ganglia, suggesting retinal examination may be a useful method to study brain health changes related to SVD.

Highlights: Optic disc pallor is linked to enlarged perivascular spaces in basal ganglia.There is no association between peripapillary retinal nerve fiber layer thickness and cerebral small vessel disease markers.Optic disc examination could provide insights into brain health.The sample included 108 midlife adults from the PREVENT Dementia study.

Introduction: Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain.

Methods: We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (APOE) ε4 allele carriers). Cognitive decline was assessed annually across 6 years using modified Mini-Mental State Examination (3MSE) and Digital Symbol Substitution Test (DSST). Additionally, a subset of 3050 participants were followed for clinically adjudicated dementia.

Results: Higher plasma levels of sphingomyelin-d18:1/16:0 (SM-16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin-d18:1/22:0 (SM-22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM-16 (hazard ration [HR] = 1.24 [95% confidence interval [CI]: 1.08-1.44]) and ceramide-d18:1/16:0 (Cer-16) (HR = 1.26 [95% CI: 1.10-1.45]) were associated with higher risk of incident dementia.

Discussion: Several sphingolipid species appear to be involved in cognitive decline and dementia risk.

Highlights: Plasma levels of sphingolipids were associated with cognitive decline and dementia risk.Ceramides and sphingomyelins with palmitic acid were associated with faster annual cognitive decline and increased risk of dementia.The direction of association depended on the covalently bound saturated fatty acid chain length in analysis of cognitive decline.

Introduction: A subset of people with Parkinson's disease (PD) develop dementia faster than others. We aimed to profile PD cognitive subtypes at risk of dementia based on their rate of cognitive decline.

Method: Latent class mixed models stratified subtypes in Parkinson's Progression Markers Initiative (PPMI) (N = 770) and ICICLE-PD (N = 212) datasets based on their decline in the Montreal Cognitive Assessment over at least 4 years. Baseline demographic and cognitive data at diagnosis were compared between subtypes to determine their clinical profile.

Results: Four subtypes were identified: two with stable cognition, one with steady decline, and one with rapid decline. Performance on Judgement of Line Orientation, but not category fluency, was associated with a steady decline in the PPMI dataset, and deficits in category fluency, but not visuospatial function, were associated with a steady decline in the ICICLE-PD dataset.

Discussion: People with PD susceptible to cognitive decline demonstrate unique clinical profiles at diagnosis, although this differed between cohorts.

Highlights: Four cognitive subtypes were revealed in two Parkinson's disease samples.Unique profiles of cognitive impairment were related to cognitive decline.Judgement of Line Orientation/category fluency predictive of steady decline.Global deficits related to rapid cognitive decline and increased dementia risk.

Introduction: Depression and its components significantly impact dementia prediction and severity, necessitating reliable objective measures for quantification.

Methods: We investigated associations between emotion-based speech measures (valence, arousal, and dominance) during picture descriptions and depression dimensions derived from the geriatric depression scale (GDS, dysphoria, withdrawal-apathy-vigor (WAV), anxiety, hopelessness, and subjective memory complaint).

Results: Higher WAV was associated with more negative valence (estimate = -0.133, p = 0.030). While interactions of apolipoprotein E (APOE) 4 status with depression dimensions on emotional valence did not reach significance, there was a trend for more negative valence with higher dysphoria in those with at least one APOE4 allele (estimate = -0.404, p = 0.0846). Associations were similar irrespective of dementia severity.

Discussion: Our study underscores the potential utility of speech biomarkers in characterizing depression dimensions. In future research, using emotionally charged stimuli may enhance emotional measure elicitation. The role of APOE on the interaction of speech markers and depression dimensions warrants further exploration with greater sample sizes.

Highlights: Participants reporting higher apathy used more negative words to describe a neutral picture.Those with higher dysphoria and at least one APOE4 allele also tended to use more negative words.Our results suggest the potential use of speech biomarkers in characterizing depression dimensions.

Easily applied diagnostic tools such as digital biomarkers for Alzheimer's disease (AD) are urgently needed due to the recent approval of disease-modifying therapies. We aimed to determine the diagnostic performance of hand-held, quantitative light reflex pupillometry (qLRP) in patients with AD in a proof-of-concept, cross-sectional study. Participants underwent qLRP at a university memory clinic from August 2022 to October 2023. We fitted multivariable logistic regression models with qLRP, sex, and age as predictors evaluated with area under the receiver operating characteristics curve (AUROC). In total, 107 patients with AD, 44 patients with mixed AD and vascular cognitive dysfunction (VCD), 53 patients with dementia with Lewy bodies (DLB), and 50 healthy controls (HCs) were included. Our diagnostic models showed similar discriminatory ability (AUROC range 0.74-0.81) when distinguishing patients with AD from HCs and other dementias. The qLRP seems promising as a bedside digital biomarker to aid in diagnosing AD.

Highlights: We demonstrated the diagnostic performance of qLRP in Alzheimer's disease.The diagnostic models were robust in sensitivity analyses.qLRP may assist in the bedside diagnostic evaluation of Alzheimer's disease.