Dissociation of neuropathology from severity of dementia in late-onset Alzheimer disease.
BACKGROUND
Little is known about Alzheimer disease at advanced ages, although its incidence continues to increase at least through the ninth decade of life.


OBJECTIVE
To examine the effects of age on the relationship between clinical dementia severity and neuropathologic hallmarks in a large sample spanning the full age range.


METHODS
The authors assessed 81 subjects during life for dementia severity, and examined their brains. They analyzed plaque and tangle burden, as well as the activities of the cholinergic marker enzymes acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), in relation to age at death and the clinical severity of dementia.


RESULTS
Dementia severity was strongly related to plaque and tangle burden in relatively young patients (aged < 75 years), but this correlation diminished with age and disappeared in the ninth decade of life. Among the oldest patients studied, there was no difference in plaque and tangle load between the mild and severe dementia cases. This interaction (p < 0.0001 for plaque density) was not observed for the cholinergic markers ChAT and AChE.


CONCLUSIONS
The nature or expression of Alzheimer disease may be different in severely demented older patients, who have equal cholinergic deficits but significantly lower plaque and tangle burden. If confirmed in a prospective study, these findings have diagnostic and therapeutic implications.
Prohovnik
I
I
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA. isak.prohovnik@mssm.edu
Perl
D P
DP
Davis
K L
KL
Libow
L
L
Lesser
G
G
Haroutunian
V
V
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests
D015415:Biomarkers; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine