A5057288205- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- Metabolomics and Mass Spectrometry Studies
- Bioinformatics and Genomic Networks
- Health, Environment, Cognitive Aging
- Clusterin in disease pathology
- Nutrition, Genetics, and Disease
- Traditional Chinese Medicine Studies
- Functional Brain Connectivity Studies
- Folate and B Vitamins Research
- Cognitive Abilities and Testing
- Nerve injury and regeneration
- Salivary Gland Disorders and Functions
- Neurological Disease Mechanisms and Treatments
- Blood Pressure and Hypertension Studies
- Memory and Neural Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Adipokines, Inflammation, and Metabolic Diseases
- Personality Traits and Psychology
- RNA regulation and disease
- Bipolar Disorder and Treatment
- Nuclear Receptors and Signaling
- Neurobiology of Language and Bilingualism
- Cardiovascular Health and Risk Factors
- Nutritional Studies and Diet
University of California, Davis
2022-2025
Sunnybrook Research Institute
2017-2021
Sunnybrook Health Science Centre
2018-2021
Health Sciences Centre
2018-2021
Sunnybrook Hospital
2017-2020
University of Toronto
2017-2019
University of Alberta
2014-2018
Women and Children’s Health Research Institute
2014-2018
ABSTRACT Objective To profile the amine/phenol submetabolome to determine potential metabolite biomarkers associated with Parkinson's disease (PD) and PD incipient dementia. Methods At baseline of a 3‐wave (18‐month intervals) longitudinal study, serum samples were collected from 42 healthy controls 43 patients. By wave 3 (year 3), 16 patients diagnosed dementia classified as at baseline. Metabolomic profiling using dansylation isotope labeling liquid chromatography mass spectrometry was...
Using a non-invasive biofluid (saliva), we apply powerful metabolomics workflow for unbiased biomarker discovery in Alzheimer's disease (AD). We profile and differentiate Cognitively Normal (CN), Mild Cognitive Impairment (MCI), AD groups. The involves differential chemical isotope labeling liquid chromatography mass spectrometry using dansylation derivatization in-depth profiling of the amine/phenol submetabolome. total sample (N = 109) was divided to Discovery Phase (DP) (n 82; 35 CN, 25...
BACKGROUND: Modifiable risk factors play a central role in the development and course of neurodegenerative disorders later life, including dementias. Although past research has focused on independent associations modifiable factors, cardiovascular disease using Framingham score, physical activity, dietary quality, body mass index, sleep, neurodegeneration, impact all 5 simultaneously multimodal model not been studied. We examined an overall combined with white matter injury, recognized...
Background: Among the neurodegenerative diseases of aging, sporadic Alzheimer's disease (AD) is most prevalent and perhaps feared. With virtually no success at finding pharmaceutical therapeutics for altering progressive AD after diagnosis, research attention increasingly directed discovering biological other markers that detect risk in long asymptomatic phase. Both early detection precision preclinical intervention require systematic investigation multiple modalities combinations AD-related...
ABSTRACT Parkinson's disease (PD) patients are treated with levodopa ( l ‐dopa) to help stabilize their impaired motor abilities; however, ‐dopa leads increased homocysteine (Hcy) levels, which may have a deleterious effect on brain structure and function. The purpose of this study was examine the impact Hcy concentration global atrophy as determined by magnetic resonance imaging in PD controls. high level ventricular dilatation (percentage intracranial volume [%ICV]) total tissue (%ICV)...
Background: Trajectories of complex neurocognitive phenotypes in preclinical aging may be produced differentially through selective and interactive combinations genetic risk. Objective: We organize three possible into a “network” risk indices derived from polymorphisms associated with normal impaired cognitive aging, as well Alzheimer’s disease (AD). Specifically, we assemble examine clusters relevant to non-demented trajectories: 1) Apolipoprotein E ( APOE), 2) Cognitive Aging Genetic Risk...
Abstract The Hispanic/Latino population is one of the largest and most diverse ethnoracial groups in United States at high risk for dementia. We examined cognitive constructs associations with subsequent hippocampal volume (HV) white matter hyperintensity (WMHV). Participants were from Hispanic Community Health Study/Study Latinos–Magnetic Resonance Imaging Study ( n = 2029). confirmatory factor analysis longitudinal invariance using neurocognitive scores Visits 1 (2008–2011) 2 (2014–2018)...
Objectives Recent research has linked psychological (personality) factors and specific genetic risk polymorphisms to performance on neurocognitive phenotypes. We examined whether episodic or semantic memory is associated with (a) three personality traits (i.e. neuroticism, extraversion, openness experience), (b) two neurodegenerative‐related Apolipoprotein E ( APOE ; rs7412; rs429358), Clusterin CLU rs11136000)), (c) cross‐domain interactions (magnification effects). Methods Linear growth...
Interindividual differences in cognitive reserve (CR) are associated with complex and dynamic clinical phenotypes observed impairment dementia. We tested whether (1) CR early life (E-CR; measured by education IQ), (2) later (L-CR; occupation), (3) panel (CR-P) the additive effects of E-CR L-CR, act as moderating factors between baseline ventricular size dementia severity at across 2 years. further examined this moderation is differentially represented sex. a longitudinal model using patients...
Understanding the neurobiological underpinnings between established multimodal dementia risk factors and noninvasive blood-based biomarkers may lead to greater precision earlier identification of older adults at accelerated decline dementia. We examined whether key vascular genetic impact association cerebral amyloid burden plasma aβ (amyloid β) 42/40 in nondemented adults.
Abstract Introduction We examine whether distinct brain atrophy patterns (using parenchymal fraction [BPF]) differentially predict functional performance and decline in Alzheimer's disease (AD), are independently moderated by (1) a key AD genetic risk marker (apolipoprotein E [ APOE ]), (2) sex, (3) high‐risk group (women ɛ4 carriers). Methods used 2‐year longitudinal sample of patients (baseline N = 170; mean age 71.3 [9.1] years) from the Sunnybrook Dementia Study. applied latent class...
Metabolomics is a global approach to detecting perturbations in metabolic pathways that can reflect early and subtle disease-related changes the central nervous system. The metabolome, end product of gene-environment interactions, characterize discriminate signatures Alzheimer's disease (AD) Mild Cognitive Impairment (MCI). We previously established technology for using salivary samples discriminating normal cognitive aging (NA) from MCI groups. report pairwise metabolomics comparisons among...
Abstract Etiological and clinical heterogeneity is increasingly recognized as a common characteristic of Alzheimer’s disease related dementias. This complicates diagnosis, treatment, the design testing new drugs. An important line research discovery multimodal biomarkers that will facilitate targeting subpopulations with homogeneous pathophysiological signatures. High-throughput ‘omics’ are unbiased data driven techniques probe complex etiology from multiple levels (e.g. network, cellular,...
Abstract Background Associations between cognition and brain markers of amyloid, tau, neurodegeneration are poorly understood in the oldest‐old (>90 years) compared to younger populations. Prior work suggests that link neuropathology may become weaker advanced old age, reducing applicability accepted biomarker cascade models Alzheimer’s disease progression. Addressing this question is challenging, partly due limited data methodological challenges neuroimaging analysis. In study, we...
Abstract Background Neurocognitive trajectories in normal aging are a result of complex and synergistic associations multiple risk domains. Blood‐based, neuroimaging, genetic biomarkers all play fundamental roles that span decades leading to cognitive decline. We study three domains on memory using an ethnoracially diverse cohort. Specifically, we examine (1) independent plasma Neurofilament Light (pNfL) levels white matter hyperintensity volume (WMHV) episodic (EM), (2) pNfL WMHV, (3) model...
Abstract Background Genome‐wide association studies (GWAS) for established clinical dementia phenotypes is often limited to Caucasians from European ancestry. Although the incidence of higher in African Americans and Hispanics, inclusion these groups GWAS research less common. We examine an ethoracially diverse cohort older adults. Method used older‐adult University California, Davis‐Alzheimer’s Disease Research Center (n=1014; mean age= 74.54 (7.50) years; 59.6% female). Participants were...
Abstract Background Serum AD biomarkers are becoming useful to the early and accurate diagnosis of neurodegenerative disease, but much this work has been done with clinic‐based studies mostly non‐Hispanic Whites. For study, we examined relations between plasma Aβ 42/40, pTau 181, NfL, GFAP, ApoE genotype cognitive state in SOL‐INCA‐MRI study. Given that prior SOL‐INCA found vascular risk be associated mild impairment 1 , included measured by Framingham CVD score 2 white matter hyperintensity...
Differential cognitive trajectories in Alzheimer's disease (AD) may be predicted by biomarkers from multiple domains.In a longitudinal sample of AD and AD-related dementias patients (n = 312), we tested whether 1) change brain morphometry (ventricular enlargement) predicts differential trajectories, 2) further risk is contributed genetic (Apolipoprotein E [APOE] ɛ4+) vascular (pulse pressure [PP]) factors separately, 3) the + moderates this pattern.We applied dynamic computational approach...
Risk factors (and their synergistic interactions) associated with Alzheimer's disease (AD) may predict normal or preclinical deficits and decline. Although ApoE (rs429358, rs7412) is the gene most consistently linked AD risk, genome-wide association studies have identified others, including CLU (rs11136000), CR1 (rs6656401), PICALM (rs541458). Type 2 diabetes (T2D) a risk factor for increased cognitive in nondemented older adults. We examined if effect of on neurocognitive speed performance...