Pathologic and nicotinic receptor binding differences between mild cognitive impairment, Alzheimer disease, and normal aging.
BACKGROUND
Neurochemical and pathologic studies show that mild cognitive impairment (MCI) is frequently a transitional state between normal aging and Alzheimer disease (AD). Neuropathologic sample sizes have been limited because relatively few individuals with MCI die before dementia develops. Decreased neocortical nicotinic receptor binding is characteristic of AD but has not been investigated in subjects with MCI.


OBJECTIVE
To assess nicotinic receptor binding and pathologic differences in control subjects with no dementia (ND) and in subjects with clinically and pathologically described MCI or Alzheimer disease.


METHODS
This was a clinicopathologic analysis. Subjects with ND had no demonstrable cognitive or functional impairment. Subjects with MCI met Petersen clinical criteria for single- or multiple-domain amnestic MCI and died before the disorder progressed to AD. Subjects with AD met National Institute for Neurological Diseases and Stroke/Alzheimer's Disease and Related Disorders Association clinical criteria for AD. All subjects underwent a complete diagnostic and semiquantitative neuropathologic examination. Data were examined after both clinical and histopathologic classification of subjects.


METHODS
Sun Health Research Institute Brain Donation Program, and Arizona Alzheimer Disease Center.


METHODS
Twenty-one control subjects with ND, 8 subjects with MCI, and 70 subjects with AD, prospectively followed up to autopsy.


METHODS
Nicotinic acetylcholine receptor binding value, total tangle density, total plaque density, and Braak stage.


RESULTS
At the last examination before death, subjects with AD were significantly younger, less educated, and more cognitively and globally impaired compared with subjects with ND. When categorized by clinical diagnosis, MCI was always intermediate between ND and AD. On the whole, MCI was pathologically intermediate between ND and AD for senile plaque density, neurofibrillary tangle density, and Braak stage, but some subjects with MCI lacked neuritic plaques entirely. Binding for nicotinic acetylcholine receptors did not differ between the ND and MCI groups, but it was significantly less in the AD group.


CONCLUSIONS
Most MCI may be considered a transitional state between ND and AD clinically and neuropathologically, but in some MCI cases there is lack of neuritic plaques, and, therefore, it cannot be considered early AD. Nicotinic receptor binding seems to be lost during the transition from MCI to AD.
Sabbagh
Marwan N
MN
Cleo Roberts Center for Clinical Research, Sun Health Research Institute, Sun City, AZ 85351, USA. Marwan.sabbagh@sunhealth.org
Shah
Flora
F
Reid
Richard T
RT
Sue
Lucia
L
Connor
Donald J
DJ
Peterson
Lars Kristofer N
LK
Beach
Thomas G
TG
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D001921:Brain / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D004493:Education; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D018722:Nicotinic Agonists / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C082748:epibatidine