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William Bondareff, PhD, MD; Christopher Q. Mountjoy, FRCPsych; Claude M. Wischik, MD, PhD; Douglas L. Hauser; Laurie D. LaBree; Martin Roth, MD, ScD, FRCP, FRCPsych (UK)

Arch Gen Psychiatry. 1993;50(5):350-356.

Abstract
Objective
Because age of onset does not reliably define two subtypes of Alzheimer's disease, classification based on the severity of neuronal degeneration was tested.

Design
Numbers of extracellular tangles and pyramidal neurons in the hippocampus were used to group patients.

Patients
The study population consisted of 46 elderly patients satisfying DSM-III criteria for dementia and NINCDS-ADRDA criteria for definite Alzheimer's disease after death.

Results
Univariate logistic regression analysis showed the numbers of neurofibrillary tangles and pyramidal neurons and the duration of dementia were significantly as- sociated with grouping based on the presence of abundant extracellular tangles. Ninety-one percent of patients were correctly classified as compared with 85% correctly classified by age of onset data. Odds ratios showed that increasing numbers of neurofibrillary tangles predicted greater severity of neuronal loss.

Conclusion
The results of the study indicate the importance of neurofibrillary degeneration, not the deposition of amyloid, in the pathogenesis of Alzheimer's disease. They support a classification of Alzheimer's disease related more closely to the severity of neurofibrillary degeneration than to age at onset.

Author Affiliations
From the Department of Psychiatry and Behavioral Sciences, Division of Geriatric Psychiatry (Dr Bondareff and Mr Hauser), and Department of Biometry (Ms LaBree), University of Southern California School of Medicine, Los Angeles; St Andrew's Hospital, Northampton, England (Dr Mountjoy); and Department of Psychiatry, University of Cambridge (England) Clinical School (Drs Wischik, Mountjoy, and Roth). Dr Wischik is a Lister Institute Research Fellow.

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