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Amyloid deposition and brain structure as long-term predictors of MCI, dementia, and mortality

Oscar L Lopez1, James T Becker2, YueFang Chang2

  • 1From the Departments of Neurology (O.L.L., J.T.B., B.S., M.I.), Psychiatry (O.L.L., J.T.B., W.E.K., H.J.A., A.D.C.), Psychology (J.T.B.), Neurosurgery (Y.C.), Epidemiology, Graduate School of Public Health (Y.C., L.H.K.), Radiology (C.M., J.P.), Pharmaceutical Sciences (C.M.), and Genetics (M.I.K.), University of Pittsburgh, School of Medicine, PA; and Department of Neurology (S.T.D.), University of Florida, Gainesville. lopezol@upmc.edu.

Neurology
|April 27, 2018
PubMed
Abstract

Insights

Multiple brain biomarkers, including hippocampal volume, white matter lesions, and amyloid deposition, predict long-term dementia risk in older adults. The presence of more than one biomarker significantly increases dementia progression and mortality risk.

Area of Science:

  • Neurology
  • Neuroimaging
  • Gerontology

Background:

  • Cognitive decline and dementia pose significant public health challenges, particularly in aging populations.
  • Identifying reliable predictors of dementia onset and progression is crucial for early intervention and management.
  • Brain structural integrity, white matter lesions, and amyloid deposition are implicated in neurodegenerative processes.

Purpose of the Study:

  • To investigate the association of hippocampal volume, white matter lesions (WMLs), and beta-amyloid deposition with the long-term risk of incident dementia and mortality.
  • To determine if these biomarkers are independent predictors of dementia and mortality in individuals aged 80 years and older.
  • To assess the cumulative effect of these biomarkers on dementia risk.

Main Methods:

  • Longitudinal study involving 183 cognitively normal individuals and patients with mild cognitive impairment (MCI) aged 80+.
  • Brain structural MRI and amyloid PET scans (using 11C-Pittsburgh compound B) were conducted in 2009.
  • Participants were followed annually through 2015 (mean 5.2 years) for cognitive status and mortality.

Main Results:

  • All three biomarkers (hippocampal volume, WMLs, amyloid deposition) independently predicted incident dementia.
  • Amyloid deposition and WMLs were stronger predictors of dementia than hippocampal volume after adjusting for mortality risk.
  • Individuals with three positive biomarkers had a 75% progression to dementia, versus 16% for those with no biomarker positivity.
  • Hippocampal volume and amyloid deposition were associated with mortality specifically in MCI participants.

Conclusions:

  • The presence of multiple biomarkers significantly enhances the prediction of long-term dementia risk compared to single biomarkers.
  • Amyloid deposition and WMLs are robust predictors of dementia, even after accounting for mortality.
  • Neurodegeneration and amyloid deposition, particularly in individuals with MCI, are associated with an increased risk of death during follow-up.

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