Traditionally, schizophrenia has been studied in early adulthood. Its
course and outcome during senescence are largely unknown and subject t
o controversy. We reviewed the consecutive neuropathologic records of
1,046 patients who were chronically hospitalized in New York State men
tal institutions, and we selected for analysis all 802 patients who di
ed after age 50 with a clinical antemortem diagnosis, as recorded in t
he autopsy notes, of schizophrenia (n = 544) or dementia (n = 258). Th
e prevalence of neuropathologic diagnoses consistent with Alzheimer's
disease (AD) was 51 percent in the dementia group and 28 percent in th
e schizophrenia sample. This prevalence rate in the schizophrenia samp
le (mean age = 77) was considerably higher than that estimated for the
general population. When evaluated against age of death, AD findings
in demented patients were age invariant, whereas the rate of such find
ings in schizophrenia patients rose monotonously from under 5 percent
below age 60 to 50 percent at age 90 and over. The age-relative rate o
f AD diagnosis in schizophrenia patients was similar to a curve postul
ated for first-degree relatives of familial AD patients and was marked
ly higher than population estimates. These findings as a basis for com
parison with other retrospective studies of pathological records are p
resented. Our own study, as well as others, suffers from three intrins
ic limitations. The clinical diagnoses are taken from death notes and
have no formal verification. Likewise, neuropathologic diagnoses were
based upon informal criteria in use at the time; since that time, form
al diagnostic criteria have been evolving, and new staining methods ha
ve become available. Finally, it is not possible to determine from thi
s material whether these patients are representative of all elderly sc
hizophrenia patients or even of those who are institutionalized. There
fore, despite the large sample size on which our current findings are
based, a new study has begun to address these weaknesses by complete r
eview and rediagnosis of medical records and neuropathological materia
l, using current methods, standardized criteria, and quantitative meas
ures of degenerative changes. Specifically, the new ongoing study exam
ines whether autopsied patients are representative by performing detai
led diagnostic reviews of a control sample of nonautopsied patients fr
om the same institutions. These results, if confirmed in the new study
, demonstrate substantially greater vulnerability of chronic schizophr
enia patients to the development of AD (or, at least, to histological
changes typical of this disease). Possible association with chronic ne
uroleptic treatment and pathophysiological mechanisms remains to be el
ucidated.