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Evidence of Subtypes of Alzheimer's Disease and Implications for Etiology

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. doi:10.1001/archpsyc.1993.01820170028004.
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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.

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