Clinical dementia rating performed several years prior to death predicts regional Alzheimer's neuropathology.
OBJECTIVE
To assess the relationships between early and late antemortem measures of dementia severity and Alzheimer disease (AD) neuropathology severity.


METHODS
40 residents of a nursing home, average age at death 82.0, participated in this longitudinal cohort study with postmortem assessment. Severity of dementia was measured by Clinical Dementia Rating (CDR) at two time points, averaging 4.5 and 1.0 years before death. Densities of postmortem neuritic plaques (NPs) and neurofibrillary tangles (NFTs) were measured in the cerebral cortex, hippocampus, and entorhinal cortex.


RESULTS
For most brain areas, both early and late CDRs were significantly associated with NPs and NFTs. CDRs assessed proximal to death predicted NFTs beyond the contribution of early CDRs. NPs were predicted by both early and late CDRs. NPs were predictive of both early and late CDRs after controlling for NFTs. NFTs were only associated significantly with late CDR in the cerebral cortex after controlling for NPs.


CONCLUSIONS
Even if assessed several years before death, dementia severity is associated with AD neuropathology. NPs are more strongly associated with dementia severity than NFTs. NFTs consistently associate better with late than early CDR, suggesting that these neuropathological changes may occur relatively later in the course of the disease.
Schnaider Beeri
Michal
M
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. michal.beeri@mssm.edu
Silverman
Jeremy M
JM
Schmeidler
James
J
Wysocki
Michael
M
Grossman
Hillel Z
HZ
Purohit
Dushyant P
DP
Perl
Daniel P
DP
Haroutunian
Vahram
V
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000401:mortality* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D003072:Cognition Disorders / Q000401:mortality* / Q000473:pathology*; D018728:Entorhinal Cortex / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D011237:Predictive Value of Tests; D012720:Severity of Illness Index