Alzheimer's & Dementia最新文献

INTRODUCTION

Sharing clinical research data is essential for advancing Alzheimer's disease (AD) research, yet challenges in accessibility, standardization, documentation, usability, and reproducibility persist.

METHODS

We developed R data packages to streamline access to curated datasets from key AD studies. A4LEARN includes data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) randomized trial and its companion observational study, the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN). ADNIMERGE2 contains curated data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a longitudinal biomarker and imaging study.

RESULTS

These packages bundle data, documentation, and reproducible analysis vignettes into portable, analysis-ready formats that can be installed and used within R. We also introduce the alzverse package, which applies a common data standard to integrate study-specific packages and facilitate meta-analyses.

DISCUSSION

By promoting collaboration, transparency, and reproducibility, R data packages provide a scalable framework to accelerate AD clinical research.

Highlights

INTRODUCTION

Alzheimer's disease (AD) often co-occurs with depression, affecting cognitive function and quality of life. Understanding the neurobiological links between brain abnormalities and depressive symptoms is essential for effective treatment.

METHODS

We analyzed 2,722 participants from the National Alzheimer's Coordinating Center, including 886 AD patients and 1,836 cognitively normal controls. Neuroimaging assessed brain volumes, while depressive symptoms were measured using the Geriatric Depression Scale. Multiple linear regression and mediation analyses evaluated associations between brain structure, cognitive function, and depression.

RESULTS

AD patients had significantly higher rates of depressive symptoms (35.3% vs. 14.7%; p < 0.001) and cognitive impairments (mean Mini-Mental State Examination [MMSE]: 23.1 vs. 28.9; p < 0.001). Hippocampal atrophy mediated the relationship between depression and AD (indirect effect = −0.107; p < 0.001).

CONCLUSION

Hippocampal atrophy significantly mediates the relationship between depression and AD, suggesting targeted interventions may enhance patient outcomes.

INTRODUCTION

Little is known about genetic risk factors for dementia in South Asians. Examining genetic variants that occur at higher frequency in India compared to other ancestries (i.e., Indian enriched variants) may identify genetic associations with cognitive function that are potentially unique to the Indian population.

METHODS

We examined whether 3.43 million variants enriched in India compared to European (EA), East Asian (EAS), and African (AFR) ancestries were associated with seven measures of cognitive function in 2680 older adults from the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD).

RESULTS

Identified Indian-enriched variants were largely near loci previously associated with neuropsychiatric traits, N-acetyltaurine levels, educational attainment, and cardiovascular risk factors for dementia. Several variants near genes previously associated with intellectual disabilities and synaptic function exhibited sex-specific effects.

DISCUSSION

Indian-enriched variants may play a significant role in cognitive function in South Asians living in India.

Highlights

INTRODUCTION

Sleep–wake disturbances frequently occur at early stages of Alzheimer's disease (AD) and accelerate disease progression, but the underlying neural mechanisms are not fully understood.

METHODS

We examined sleep–wake behavior and locus coeruleus (LC) activity in young 5xFAD mice using electrophysiology and pharmacological approaches targeting adrenergic signaling and potassium channels.

RESULTS

5xFAD mice displayed dark phase–specific hyperarousal and impaired brain state transitions by 2 months of age. LC neurons exhibited increased tonic firing due to impaired Kv4 and Kv7 potassium channel conductance, resulting from soluble amyloid beta (Aβ)-induced disruption of α2A adrenergic receptor regulation. Pharmacological activation of α2A adrenergic receptors restored Kv4/7 function and normalized LC excitability. Local administration of guanfacine (α2A agonist) or retigabine (Kv7 modulator) significantly rescued sleep–wake disturbances.

DISCUSSION

These findings identify LC hyperexcitability as a mechanistic driver of early sleep disruption in AD and implicate α2A receptors and Kv7 channels as promising therapeutic targets for early intervention.

The development of non-pharmacological treatment approaches is supported by evidence that addressing key modifiable risk factors may prevent or delay up to 45% of dementia cases. The Charlie and Harriet Shaffer Cognitive Empowerment Program (CEP) was developed to address current gaps in access to, and evidence for, interventions that reduce lifestyle risk factors and improve quality of life in individuals with mild cognitive impairment (MCI). Co-designed with patients and families, clinicians, researchers, and industry professionals, the CEP is situated in a conceptual framework that guides assessments and interventions/supports to holistically address the experience of living with MCI. CEP comprises four cores (Therapeutic Programs, Technology, Built Environment, and Innovation Accelerator) that map to the conceptual framework. We contend that our approach provides an opportunity to contribute to the evidence base for multidomain lifestyle programs and gain a deeper understanding of MCI and how individuals can be empowered to manage it.

Highlights