Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment

Ann Neurol. 1991 Oct;30(4):572-80. doi: 10.1002/ana.410300410.


We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of 15 patients with Alzheimer's disease and 9 neuropathologically normal subjects. The statistical data show only weak correlations between psychometric indices and plaques and tangles, but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique reveals very powerful correlations with all three psychological assays. Multivariate analysis by stepwise regression produced a model including midfrontal and inferior parietal synapse density, plus inferior parietal plaque counts with a correlation coefficient of 0.96 for Mattis's Dementia Rating Scale. Plaque density contributed only 26% of that strength.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / psychology
  • Analysis of Variance
  • Cognition Disorders / etiology
  • Cognition Disorders / pathology*
  • Humans
  • Middle Aged
  • Neuropsychological Tests
  • Regression Analysis
  • Synapses / pathology*