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Neurology. 2017 May 9;88(19):1814-1821. doi: 10.1212/WNL.0000000000003916. Epub 2017 Apr 12.

Neuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer disease.

Author information

1
From the Translational Neuroimaging Laboratory (K.P.N., T.A.P., S.M., C.-O.C., A.L.B., M.S., M.S.K., P.R.-N.) and Alzheimer's Disease Research Unit (K.P.N., X.L., M.B., P.R.-N., S.G.), McGill University Research Centre for Studies in Aging, Montreal, Quebec, Canada; Department of Neurology (K.P.N., N.K.), National Neuroscience Institute, Singapore; Montreal Neurological Institute (P.R.-N.); Department of Neurology and Neurosurgery (P.R.-N.), McGill University, Montreal, Quebec, Canada; Department of Neurology (X.L.), The Second Affiliated Hospital of Chongqing Medical University, Chongqing; and Department of Neurology (M.B.), Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, PR China.
2
From the Translational Neuroimaging Laboratory (K.P.N., T.A.P., S.M., C.-O.C., A.L.B., M.S., M.S.K., P.R.-N.) and Alzheimer's Disease Research Unit (K.P.N., X.L., M.B., P.R.-N., S.G.), McGill University Research Centre for Studies in Aging, Montreal, Quebec, Canada; Department of Neurology (K.P.N., N.K.), National Neuroscience Institute, Singapore; Montreal Neurological Institute (P.R.-N.); Department of Neurology and Neurosurgery (P.R.-N.), McGill University, Montreal, Quebec, Canada; Department of Neurology (X.L.), The Second Affiliated Hospital of Chongqing Medical University, Chongqing; and Department of Neurology (M.B.), Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, PR China. serge.gauthier@mcgill.ca.

Abstract

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 [18F]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 [18F]fluorodeoxyglucose (FDG) PET.

RESULTS:

Individuals with preclinical AD with higher NPI scores had higher [18F]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.

PMID:
28404803
PMCID:
PMC5419982
DOI:
10.1212/WNL.0000000000003916
[Indexed for MEDLINE]
Free PMC Article

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