Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.
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.
Terry
R D
RD
Department of Neurosciences, University of California-San Diego, La Jolla 92093-0624.
Masliah
E
E
Salmon
D P
DP
Butters
N
N
DeTeresa
R
R
Hill
R
R
Hansen
L A
LA
Katzman
R
R
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000523:psychology; D000704:Analysis of Variance; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D009483:Neuropsychological Tests; D012044:Regression Analysis; D013569:Synapses / Q000473:pathology*