Microbleeds do not affect rate of cognitive decline in Alzheimer disease

Neurology. 2012 Aug 21;79(8):763-9. doi: 10.1212/WNL.0b013e3182661f91. Epub 2012 Aug 8.

Abstract

Objective: To investigate the relationship between brain microbleeds (MBs) and the rate of cognitive decline in Alzheimer disease (AD).

Methods: In this cohort study, we studied 221 patients with AD with available baseline MRI scans (1.0 or 1.5 T) and at least 2 Mini-Mental State Examinations (MMSE) scores obtained more than 1 year apart from our memory clinic. Mean ± SD follow-up time was 3 ± 1 years, and patients had a median of 4 MMSE scores (range 2-17). We used linear mixed models with sex and age as covariates to investigate whether MBs influenced the rate of cognitive decline.

Results: Mean age was 68 ± 9 years, 109 (49%) patients were female, and the baseline MMSE score was 22 ± 4. There were 39 patients (18%) with MBs (median 2, range 1-27) and 182 without. Linear mixed models showed that overall patients declined 2 MMSE points per year. We found no association of the presence of MBs with baseline MMSE or change in MMSE. Adjustment for atrophy, white matter hyperintensities, lacunes, and vascular risk factors did not change the results nor did stratification for MB location, APOE ε4 carriership, or age at onset (≤65 years vs >65 years). Repeating the analyses with number of MBs as predictor rendered similar results.

Conclusion: MBs did not influence the rate of cognitive decline in patients with AD. The formerly reported increased risk of mortality in patients with MBs seems not to be attributable to a steeper rate of decline per se but might be due to vascular events, including (hemorrhagic) stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Apolipoprotein E4 / genetics
  • Atrophy / pathology
  • Biomarkers / cerebrospinal fluid
  • Cerebral Hemorrhage / cerebrospinal fluid
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / pathology
  • Cerebral Hemorrhage / psychology*
  • Cognition Disorders / cerebrospinal fluid
  • Cognition Disorders / complications
  • Cognition Disorders / pathology
  • Cognition Disorders / psychology*
  • Cohort Studies
  • Disease Progression
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Imaging / psychology
  • Male
  • Nerve Fibers, Myelinated / pathology
  • Neuroimaging / methods
  • Neuroimaging / psychology*
  • Neuropsychological Tests / statistics & numerical data
  • Peptide Fragments / cerebrospinal fluid*
  • Risk Factors
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins