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Principal Investigator: Carmen Andreescu
Organization: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Fiscal Year: 2024
Award: $2,938,462
Funding agency: National Institute on Aging
Mild Cognitive Impairment: A Prospective Community Study. Dementia is a
leading cause of disability and death in older adults. Its incidence increases exponentially with
age. Identifying independent risk factors and valid disease markers are critical steps towards
prevention, improved diagnosis, and treatment. To enhance clinical and public health care,
these factors must be identified in population settings. We seek to extend, for a further five
years, a 15-year prospective population-based study of mild cognitive impairment (MCI) and
dementia in a low SES-area of southwestern Pennsylvania. The original richly characterized
cohort is now aged 80+, and at maximum risk for dementia; we have replenished the cohort by
recruiting additional participants currently aged 65-74, for a total current sample ~1100.
Our objective remains to identify, at the population level, risk factors for clinically
relevant adverse cognitive outcomes of MCI, cognitive decline, and progression to dementia.
We propose a new set of specific aims investigating novel disease markers in relation to these
outcomes. Our new high performing mass-spectrometry-based plasma β amyloid (Aβ) assay
holds potential for affordable non-invasive screening for Alzheimer's disease. 7T MRI brain
scans will allow in-depth imaging of cerebrovascular integrity in a subgroup and help
understand the role of small vessel disease (SVD) in cognitive decline and dementia. Non-
invasive wrist actigraphy will measure sleep-wake rhythms which we will examine in relation to
the cognitive outcomes, Aβ and SVD. GWAS and transcriptomics will allow us to examine
genome-wide genetic and gene expression data. We will assess the relationships of these three
biomarkers (Aβ, SVD, sleep), along with genomics and gene expression, and their mutual
interactions, to the clinically relevant outcomes of cognitive decline and dementia.
New light shed on mechanisms underlying these disorders, using modeling techniques to
account for biases and generalize results from sub-samples back to the entire cohort, will lead to
new insights to help reduce the public health burden of dementia.
Terms: <21+ years old><65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><A β-42><A β42><A-beta 42><A-beta42><AD dementia><Abbreviations><Abeta-42><Abeta42><Adult><Adult Human><Age><Aged 65 and Over><Alleles><Allelomorphs><Alzheimer Type Dementia><Alzheimer beta-Protein><Alzheimer disease dementia><Alzheimer disease screening><Alzheimer sclerosis><Alzheimer screening><Alzheimer syndrome><Alzheimer's><Alzheimer's Amyloid beta-Protein><Alzheimer's Disease><Alzheimer's amyloid><Alzheimer's biomarker><Alzheimer's disease biological marker><Alzheimers Dementia><Alzheimer’s biological marker><Alzheimer’s disease biomarker><Amentia><Amyloid><Amyloid Alzheimer's Dementia Amyloid Protein><Amyloid Beta-Peptide><Amyloid Protein A4><Amyloid Substance><Amyloid beta-42><Amyloid beta-Protein><Amyloid beta42><Amyloid β><Amyloid β-42><Amyloid β-Peptide><Amyloid β-Protein><Amyloid β42><Amyloidβ-42><Amyloidβ42><Area><Assay><Aβ><Aβ-42><Aβ42><Back><Bioassay><Biological Assay><Biological Markers><Bleeding><Blood><Blood Plasma><Blood Reticuloendothelial System><Brain><Brain Nervous System><Brain Vascular><Brain Vascular Disorders><Brain scan><Candidate Disease Gene><Candidate Gene><Causality><Cerebrovascular Disease><Cerebrovascular Disorders><Cessation of life><Clinical><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Cohort Studies><Communities><Concurrent Studies><Data><Death><Dementia><Diagnosis><Disease><Disease Marker><Disorder><Disturbance in cognition><Dorsum><Education><Educational aspects><Encephalon><Etiology><GWA study><GWAS><Gender><Gene Expression><Gene variant><Genes><Genetic><Genomics><Glossary><Goals><Health><Healthcare><Hemorrhage><Heterogeneity><Image><Impaired cognition><Incidence><Infarction><Intracranial Vascular Diseases><Intracranial Vascular Disorders><Investigation><Light><Literature><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Measures><Mediating><Mediation><Medical><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Mendelian randomization><Mental Depression><Microvascular Dysfunction><Modeling><NMR Imaging><NMR Tomography><Names><Negotiating><Negotiation><Nuclear Magnetic Resonance Imaging><Outcome><Participant><Pennsylvania><Photoradiation><Plasma><Plasma Serum><Population><Population Study><Predictive Factor><Prevention><Primary Senile Degenerative Dementia><Public Health><QTL><Quantitative Trait Loci><RNA Seq><RNA sequencing><RNAseq><Race><Races><Reticuloendothelial System, Serum, Plasma><Risk><Risk Factors><Risk Reduction><Role><Sampling><Selection Bias><Sleep><Sleep Wake Cycle><Subgroup><Techniques><Testing><Variant><Variation><Visualization><White Matter Hyperintensity><Woman><Work><Wrist><Zeugmatography><a beta peptide><abeta><above age 65><actigraph><actigraphy><adulthood><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age of 65 years onward><aged><aged 65 and greater><aged 65+><aged ≥65><ages><allele variant><allelic variant><amyloid beta><amyloid-b protein><beta amyloid fibril><bio-markers><biologic marker><biomarker><biomarker identification><blood loss><brain vascular disease><brain vascular dysfunction><causal diagram><causal model><causation><cerebral vascular><cerebral vascular disease><cerebral vascular dysfunction><cerebro-vascular><cerebrovascular><cerebrovascular dysfunction><cerebrovascular imaging><clinical relevance><clinically relevant><co-morbid><co-morbidity><cognitive dysfunction><cognitive loss><cognitive performance><cohort><comorbidity><dementia burden><dementia risk><depression><diagnostic criteria><differential expression><differentially expressed><disability><disease causation><genetic variant><genome scale><genome wide association><genome wide association scan><genome wide association studies><genome wide association study><genome-wide><genomewide><genomewide association scan><genomewide association studies><genomewide association study><genomic variant><health care><healthy aging><healthy human aging><human old age (65+)><identification of biomarkers><identification of new biomarkers><imaging><improved><infarct><insight><intracranial vascular dysfunction><low SES><low socio-economic position><low socio-economic status><low socioeconomic position><low socioeconomic status><marker identification><men><microvascular complications><microvascular disease><mild cognitive disorder><mild cognitive impairment><name><named><naming><new marker><novel><novel biomarker><novel marker><old age><older adult><older adulthood><outcome prediction><over 65 years><population based><population-based study><population-level study><primary degenerative dementia><prospective><racial><racial background><racial origin><recruit><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><risk factor for dementia><risk for dementia><risk-reducing><senile dementia of the Alzheimer type><sex><small vessel disease><social role><soluble amyloid precursor protein><spelling><studies of populations><study of the population><time use><transcriptional differences><transcriptome sequencing><transcriptomic sequencing><transcriptomics><whole genome association analysis><whole genome association studies><whole genome association study><≥65 years>