Neuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer disease.

TitleNeuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer disease.
Publication TypeJournal Article
Year of Publication2017
AuthorsNg KPin, Pascoal TA, Mathotaarachchi S, Chung C-O, Benedet AL, Shin M, Kang MSu, Li X, Ba M, Kandiah N, Rosa-Neto P, Gauthier S
Corporate AuthorsAlzheimer's Disease Neuroimaging Initiative
Date Published2017 May 09
KeywordsAged, Alzheimer Disease, Aniline Compounds, Apolipoprotein E4, Biomarkers, Brain, Brain Mapping, Ethylene Glycols, Female, Fluorodeoxyglucose F18, Follow-Up Studies, Humans, Irritable Mood, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Positron-Emission Tomography, Prodromal Symptoms, Prognosis, Radiopharmaceuticals, Sleep, tau Proteins

OBJECTIVE: To identify regional brain metabolic dysfunctions associated with neuropsychiatric symptoms (NPS) in preclinical Alzheimer disease (AD).METHODS: We stratified 115 cognitively normal individuals into preclinical AD (both amyloid and tau pathologies present), asymptomatic at risk for AD (either amyloid or tau pathology present), or healthy controls (no amyloid or tau pathology present) using [(18)F]florbetapir PET and CSF phosphorylated tau biomarkers. Regression and voxel-based regression models evaluated the relationships between baseline NPS measured by the Neuropsychiatric Inventory (NPI) and baseline and 2-year change in metabolism measured by [(18)F]fluorodeoxyglucose (FDG) PET.RESULTS: Individuals with preclinical AD with higher NPI scores had higher [(18)F]FDG uptake in the posterior cingulate cortex (PCC), ventromedial prefrontal cortex, and right anterior insula at baseline. High NPI scores predicted subsequent hypometabolism in the PCC over 2 years only in individuals with preclinical AD. Sleep/nighttime behavior disorders and irritability and lability were the components of the NPI that drove this metabolic dysfunction.CONCLUSIONS: The magnitude of NPS in preclinical cases, driven by sleep behavior and irritability domains, is linked to transitory metabolic dysfunctions within limbic networks vulnerable to the AD process and predicts subsequent PCC hypometabolism. These findings support an emerging conceptual framework in which NPS constitute an early clinical manifestation of AD pathophysiology.

Alternate JournalNeurology
PubMed ID28404803
PubMed Central IDPMC5419982