Journal of Alzheimer’s Disease

IntroductionThis study investigates the effects of vortioxetine on cognitive performance in patients with mild cognitive impairment (MCI) in a randomized controlled trial (RCT). MCI is characterized by memory impairment and deficits in other cognitive domains and has been found to progress into Alzheimers dementia (AD) in some cases. In a recent open-label, single-arm study, vortioxetine, an antidepressant, was associated with improved cognitive function in patients with MCI, however, no placebo...

ImportanceImpaired cognitive function is a hallmark of neuropsychiatric disease, posing a significant challenge to patients, clinicians and healthcare systems. Emerging research on ketone bodies suggests they may function as an alternative fuel for the brain, potentially enhancing cognitive function through both metabolic and signaling pathways. An alternative to inducing ketosis by lowering dietary carbohydrate intake is consumption of exogenous ketones (EK). ObjectiveIt is unknown whether the...

Genome-wide association studies (GWAS) have identified numerous Alzheimers disease (AD)- associated variants. However, how these variants contribute to the etiology of AD remains largely elusive. Recent advances in genomic large language models (LLMs) offer new opportunities to interpret the genetic variation observed in personal genome. In this study, we propose epiBrainLLM, a novel computational framework that leverages genomic LLM to enhance our understanding of the causal pathways from genot...

The urgent need for safe and effective therapies for Alzheimers disease (AD) has spurred a growing interest in repurposing existing drugs to treat or prevent AD. In this study, we combined multi-omics and clinical data to investigate possible repurposing opportunities for AD. We performed transcriptome-wide association studies (TWAS) to construct gene expression signatures of AD from publicly available GWAS summary statistics, using both transcriptome prediction models for 49 tissues from the Ge...

BackgroundAlzheimers disease (AD) is a major public health issue with rising prevalence due to global aging. In France, official estimates report a societal cost of {euro}2.3 billion, however likely underestimating the true economic burden. MethodsA comprehensive economic model was developed to estimate the ADs societal cost in France. The model incorporated diagnosis timings (early, average, late), disease stages (MCI, mild, severe AD), direct and indirect costs, and different payors. Results...

It is now acknowledged that Alzheimers Disease (AD) processes are present decades before the onset of clinical symptoms, but whether lifestyle activities can protect against these early AD processes in mid-life remains poorly understood. Furthermore, the impact of sex as a biological variable on associations between dementia risk, protective lifestyle activities and cognition is unknown. In this study, we aimed to replicate findings from our two recent studies [Deng et al. (2022) and Heneghan et...

BackgroundThe pursuit of accurate biomarkers for early detection and disease monitoring of Alzheimers disease (AD) has driven a growing interest in digital biomarkers. We aimed to map the research landscape of digital biomarkers in early AD obtained with wearable or portable digital health technologies (DHTs). MethodsIn our scoping review, we included original research on portable or wearable DHTs where digital biomarkers were measured in populations of early AD (mild cognitive impairment (MCI)...

IntroductionSeveral Mendelian randomization studies have been conducted, which identified multiple risk factors for Alzheimers disease (AD). However, they typically focus on a few pre-selected risk factors. MethodsTwo-sample Mendelian randomization (MR) study was used to systematically examine the potential causal associations of 1,054 risk factors/medical conditions and 28 drugs with the risk of late- onset AD. To correct for multiple comparisons, the false discovery rate was set at <0.05. Re...

BACKGROUNDWe investigated the association between path-integration (PI) errors related to entorhinal cortex function detectable using a 3D virtual reality (VR) navigation system and various biomarkers to explore its potential as an early AD indicator. METHODSThe PI capabilities of 111 healthy adults were assessed using a head-mounted 3D VR system. Demographic and cognitive assessments, AD-related plasma biomarkers, and apolipoprotein E genotypes were also evaluated. Predictive factors for PI er...

ObjectiveObservational studies on cognition found that vitamin D supplementation is associated with improved cognition. Further, recent Mendelian randomization (MR) studies have shown that increased vitamin D levels, as measured by 25-hydroxyvitamin D [25(OH)D], may protect against Alzheimers disease. Thus, it is possible that 25OHD may protect against Alzheimers disease by improving cognition. MethodsTo evaluate this hypothesis, we began by performing an observational study by testing the asso...

Structured abstractO_ST_ABSImportanceC_ST_ABSWomen are consistently reported to experience steeper rates after an Alzheimers disease (AD) diagnosis. We tested if this could be due to a sex-specific cognitive reserve based in verbal memory. ObjectiveTo determine whether the divergence in verbal memory trajectories from cognitively normal (CN) to AD varies by sex. DesignWe employed a longitudinal cohort design (ADNI, PREVENT-AD) to model cognitive change over time in A{beta}-CN participants vers...

BackgroundDelaying the transition from minimal cognitive impairment to Alzheimers dementia is a major concern in Alzheimers disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimers dementia. We have taken a nutritional supplement approach with genistein, a chemically defined pol...

INTRODUCTIONMild cognitive impairment (MCI), a prodromal stage of Alzheimers disease and related dementias (ADRD), represents a critical window for intervention. Although mitochondrial dysfunction is increasingly implicated in neurodegeneration, most therapies target downstream protein aggregation. Transcranial photobiomodulation (tPBM) delivers near-infrared light to enhance mitochondrial respiration. We hypothesized that tPBM in MCI would be safe, feasible, and associated with improvements in ...

It is now acknowledged that Alzheimers Disease (AD) processes are present decades before the onset of clinical symptoms, but it remains unknown whether lifestyle factors can protect against these early AD processes in mid-life. We asked whether modifiable lifestyle activities impact cognition in middle-aged individuals who are cognitively healthy, but at risk for late life AD. Participants (40-59 years) completed cognitive and clinical assessments at baseline (N = 206) and two years follow-up (N...

INTRODUCTIONThe association of blood-based biomarkers of neuropathology with cognition, dementia, and mortality and how these association potentially differ by race/ethnicity, has not been examined in large, diverse, nationally-representative samples of adults. METHODSThe sample included Health and Retirement Study (HRS) respondents over age 50 with blood-based neuropathology biomarker, demographic, and cognitive data (n=4,214). A{beta}-40, A{beta}-42, neurofilament light chain (NfL), and glial...

IntroductionAlzheimers disease (AD) is a neurodegenerative disorder characterized by cognitive decline and changes in mood and behavior. While current pharmacological treatments offer limited symptom relief, non-invasive therapies like repetitive transcranial magnetic stimulation (rTMS) have emerged as potential alternatives. This systematic review and meta-analysis aimed to assess the effects of rTMS on cognitive function, mood, and functional abilities in AD patients. MethodsA comprehensive s...

BackgroundAlzheimers disease (AD) is an intractable and multi-factorial neurodegenerative disorder. Given the globally rapid increase in obesity and its role in AD pathogenesis, understanding the impact of body weight, its changes, and the role of physical activity on AD development can provide important guidance for preventative strategies. MethodsThis population-based retrospective cohort study analyzed data from Korean national health and disability databases, including 3,741,424 individuals...

Amyloid-{beta} (A{beta}) and tau proteins accumulate within distinct neuronal systems in Alzheimers disease (AD). Although it is not clear why certain brain regions are more vulnerable to A{beta} and tau pathologies than others, gene expression may play a role. We studied the association between brain-wide gene expression profiles and regional vulnerability to A{beta} (gene-to-A{beta} associations) and tau (gene-to-tau associations) pathologies leveraging two large independent cohorts (n = 715) ...

Mild cognitive impairment (MCI) is clinical diagnosis that refers to individuals whose performance is below average on standardized cognitive tests, but who otherwise function independently in instrumental activities of daily living. Few prior studies have addressed the problem of selecting the optimal combination of behavioral instruments and cutoff scores for detecting MCI in an outpatient setting. The aim of this work is to provide insight into two related questions: (1) What is the relative ...

BackgroundThe rising prevalence of Alzheimers disease (AD) and related neurodegenerative disorders highlights the need for non-pharmacological strategies to preserve cognitive health. Brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and irisin are biomarkers associated with cognitive resilience and metabolic health. ObjectiveTo assess the impact of a multimodal lifestyle intervention on serum BDNF, VEGF, and irisin levels in an aging population, aiming to exp...