Neuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer disease

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


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.

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / psychology*
  • Aniline Compounds
  • Apolipoprotein E4 / genetics
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • 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 / cerebrospinal fluid


  • Aniline Compounds
  • Apolipoprotein E4
  • Biomarkers
  • Ethylene Glycols
  • MAPT protein, human
  • Radiopharmaceuticals
  • tau Proteins
  • Fluorodeoxyglucose F18
  • florbetapir