Accurate identification of individuals at risk for cognitive decline is critical for treatment planning and trial enrichment strategies. We evaluated the combined utility of plasma phosphorylated tau at threonine 217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in predicting domain-specific cognitive decline.

Comorbidities may influence Alzheimer's disease (AD) plasma biomarkers. This study aimed to investigate how medical conditions impact AD plasma biomarkers and whether comorbidity-adjusted models enhance their diagnostic performance.

Longitudinal data on risk factors at different ages across the lifecourse are essential for gaining important insights into how the timing and accumulation of exposure to risk factors influence the risk of Alzheimer's disease and related dementias (dementia). With increased interest in the exposome and lifecourse research questions, there have been commensurate increases in data sources and methodological approaches for answering these questions using empirical data. Methodological approaches developed within specific disciplines have largely remained within disciplinary silos, despite their potential for broader applications. By enumerating these approaches in a single place, we aim to expand discovery in lifecourse dementia research and help investigators align their research questions with appropriate analytic methods. In doing so, we seek to guide methodological decision-making and ensure that researchers use appropriate statistical tools to answer important questions about the exposome and lifecourse risk factors for dementia. HIGHLIGHTS: Longitudinal exposure data are valuable for exposome and lifecourse research on dementia. Multiple methodological approaches exist to analyze such data, with different assumptions, advantages, and disadvantages. Some methodological approaches have been used predominantly in specific disciplines but may have wider utility. Additional research is needed to integrate added complexity from the co-occurrence of multiple exposures into existing methods. Comparisons between methods help researchers make informed decisions on the appropriate method for a specific research question.

Pretangle tau inclusions from the locus coeruleus (LC) are hypothesized to propagate to the entorhinal cortex (EC) via neuron-to-neuron transmission along its projections. The lower integrity of the LC-EC pathway accompanying Alzheimer's disease (AD) pathology is supported by post mortem studies, but in vivo evidence remains limited.

Cerebrovascular injury is common in Alzheimer's disease (AD), but its timing in relation to Aβ and tau pathology and cognitive decline remains unclear.

We examined skeletal muscle adiposity (myosteatosis), a risk factor for cardiometabolic diseases, and 5-year cognitive change in White and Black middle-aged men (n = 1080; 41.9% Black) and women (n = 1432; 49.0% Black).

Core 1 biomarkers, such as amyloid positron emission tomography, capture the earliest biological changes leading to Alzheimer's disease (AD). While APOE is a major genetic factor, the contribution of other variants to Core 1 biomarkers remains unclear. The goal of this study was to determine whether genetic regulators of Core 1 biomarker levels predicted AD pathology better than genetic regulators of clinical AD.

Alzheimer's disease (AD) primarily affects episodic memory, which relies on the medial temporal lobe, including the hippocampus and lateral entorhinal cortex (LEC). However, it remains unclear whether memory deficits in AD reflect disrupted encoding of new experiences or impaired retrieval of previously stored information.

Recent studies have highlighted retinal optical coherence tomography (OCT) imaging as a promising biomarker for the early detection of Alzheimer's disease (AD). This review connects AD brain pathology - particularly amyloid beta (Aβ), tau, and vascular changes - with corresponding retinal changes. Evidence suggests that abnormal Aβ and tau deposits in the retina may reflect brain pathology, though their formation mechanisms remain unclear. Retinal vascular changes may also mirror brain pathology, with recent data emerging on other co-pathologies. Retinal thickness changes, especially in acetylcholine-producing layers, can differentiate AD from controls, although not in early AD; however, emerging high-resolution OCT techniques may enhance early detection. We find that correlations between retinal thickness and brain structures are often weak, and retinal vascular imaging shows promise in estimating cerebrovascular disease markers from retinal vascular changes. Novel imaging modalities (e.g., hyperspectral imaging) for detecting retinal Aβ deposits may improve early AD screening when combined with other biomarkers. HIGHLIGHTS: Retinal Aβ/tau is equivocal; peripheral retinal p-tau shows diagnostic promise. OCT retinal/choroid thickness diagnostic/prognostic AUC is small to medium. Hyperspectral imaging and electroretinography may aid early diagnosis. OCTA may differentiate MCI from controls, but preclinical studies are needed. The added value of retinal biomarkers for risk stratification remains uncertain.

Despite their value for public health, research, and care, population-based registries for Alzheimer's disease and related dementias (ADRD) remain limited. We conducted a scoping review of dementia registry studies through December 2023 and identified population-based dementia registries in Organisation for Economic Co-operation and Development countries. We characterized their structure and scope, assessed key themes, and developed recommendations for registry development. We identified 21 population-based dementia registries from a review of 235 publications. These registries help fill gaps in dementia research by providing longitudinal data, improving case identification, and standardizing outcomes for clinical and policy use. However, many registries lack data on healthcare use and caregiving and have limited geographical coverage, thereby reducing their ability to inform research and public health efforts to address dementia burden in an era of rapidly evolving dementia diagnostics and treatments. As dementia cases rise and advancements in prevention, detection, and treatment accelerate, population-based registries are essential for generating real-world evidence to improve dementia care, policy, and outcomes. HIGHLIGHTS: This scoping review identified 21 population-based dementia registries across OECD countries, highlighting the current landscape and structural gaps. Registries provide critical longitudinal data and standardization for research and policy but often lack information on healthcare use, caregiving, and broad geographic representation. With rising dementia rates and evolving treatments, population-based registries are essential for producing real-world evidence to strengthen care, research, and public health planning.

We determined whether mitochondrial DNA (mtDNA) depletion induced Alzheimer's disease (AD)-relevant transcription changes.

Artificial intelligence (AI) models in healthcare require accurate diagnostic data. In dementia, diagnostic ambiguity and inconsistent coding may distort data quality.

Late-life depression symptoms are implicated in dementia. We examined how cumulative burden, duration, trajectory, and variability of depression symptoms are associated with incident dementia.

We test the hypothesis that high levels of neuroplasticity in the context of Alzheimer's disease (AD) risk factors are involved in AD pathogenesis by investigating interactions between cerebrospinal fluid (CSF) levels of growth-associated protein-43 (GAP-43) and AD risk factors (female sex, cerebrovascular risk, mild cognitive impairment, apolipoprotein E [APOE] ε4 genotype, amyloid positivity) on CSF biomarkers of AD pathology (amyloid beta 42/40[Aβ42/40], phosphorylated tau (p-tau)) and neurodegeneration (tau).

The aims of this review were to assess the associations between neuropsychological test results and thyroid hormone levels, as well as the imaging abnormalities in the brain associated with hypothyroidism. For this systematic review and meta-analysis, 85 prior studies met the inclusion criteria. Among these studies, the prevalence of neurocognitive impairment assessed with the Mini-Mental State Examination (MMSE) in hypothyroidism was 0.29 [95% CI:0.26-0.33]. The pooled correlation strength between thyroid-stimulating hormone and the MMSE was r = -0.46 [95% CI:-0.69 to -0.15]. Patients with hypothyroidism performed lower than controls on the MMSE (standardized mean difference (SMD) = -1.134, [95% CI:-2.020 to -0.248]), Wechsler Memory Scale (SMD = -1.286 [95% CI:-2.110 to -0.462]), and had longer P300 latency (SMD = 1.124, [95% CI: 0.746-1.502]). Qualitative analysis of neuroimaging data indicated that drug-naïve individuals diagnosed with hypothyroidism have numerous structural and functional alterations. Meta-regressions showed that the results are dependent on both hormone levels and sociodemographic variables. Neurocognitive difficulties in individuals with hypothyroidism is a complex phenomenon that requires further investigation. HIGHLIGHTS: Neurocognitive impairment (NCI) occurs in about one third of patients with hypothyroidism. Thyroid-stimulating hormone level is negatively associated with neuropsychological test results. Memory functions in patients with hypothyroidism were lower than in the control group. Sociodemographic and clinical characteristics were moderators of NCI. Studies indicate abnormalities in the structure and metabolism of the central nervous system in patients with hypothyroidism.

Following regulatory approval of anti-amyloid beta (Aβ) therapies, a better characterization of patients receiving these treatments is needed to guide clinical management and inclusion in future trials. This Alzheimer's Association-convened workgroup proposes a terminology, treatment-related amyloid clearance (TRAC), to reflect alterations in disease pathophysiology based on biomarker evidence for clearance of Aβ deposits. TRAC designates biomarker-defined pharmacodynamic changes, rather than direct neuropathological evidence, and applies to individuals with (1) pretreatment biomarker confirmation of cerebral Aβ deposition, (2) treatment with an Aβ-targeting therapy, and (3) a follow-up biomarker test indicative of partial or full clearance of Aβ deposits. The workgroup currently recommends defining TRAC using amyloid-positron emission tomography (PET) and emphasizes the role of quantitative measurements for defining the degree of clearance. This framework is expected to be adapted over time in response to rapidly evolving biomarker and clinical advances and with the accumulation of real-world data on patients receiving anti-Aβ therapies. Highlights TRAC identifies patients with biomarker evidence for clearance of amyloid deposits. TRAC is currently defined using amyloid-PET. Full TRAC means that PET levels dropped below predetermined positivity threshold. Partial TRAC means that PET levels dropped significantly but remain above threshold. This framework is meant to guide future research on patients receiving treatment.

Selective attrition due to interwave mortality can lead to bias in studies of cognitive decline. Long interwave intervals exacerbate challenges.

This study examined whether selective serotonin reuptake inhibitors (SSRIs) treatment influenced cognitive trajectory and progression to Alzheimer's disease (AD) dementia in amnestic mild cognitive impairment (MCI) patients, stratified by AD pathology.

CLEC7A is a surface receptor that is highly upregulated on microglia in many Alzheimer's disease (AD) models. Little is known about the role that microglial CLEC7A signaling plays in AD-related pathogenesis.

Collaborative care models with care navigation bridge medical and social needs in dementia care. These models, including the Care Ecosystem (CE), are being implemented at health systems and community-based programs across the United States.

We examined how gender and lifetime occupational skill intersect cross-nationally to influence later-life cognitive function.