Neuropathological comparisons of amnestic and nonamnestic mild cognitive impairment.
BACKGROUND
Although there are studies investigating the pathologic origins of mild cognitive impairment (MCI), they have revolved around comparisons to normal elderly individuals or those with Alzheimer's disease (AD) or other dementias. There are few studies directly comparing the comprehensive neuropathology of amnestic (aMCI) and nonamnestic (naMCI) MCI.


METHODS
The database of the Brain and Body Donation Program ( www.brainandbodydonationprogram.org ), a longitudinal clinicopathological study of normal aging and neurodegenerative disorders, was queried for subjects who were carrying a diagnosis of aMCI or naMCI at the time of autopsy. Neuropathological lesions, including neuritic plaques, neurofibrillary tangles (NFTs), Lewy bodies (LBs), infarcts, cerebral white matter rarefaction (CWMR), cerebral amyloid angiopathy (CAA), and concurrent major clinicopathological diagnoses, including Parkinson's disease (PD) were analyzed.


RESULTS
Thirty four subjects with aMCI and 15 naMCI met study criteria. Subjects with aMCI were older at death (88 vs. 83 years of age, p = 0.03). Individuals with naMCI had higher densities of LBs within the temporal lobe (p = 0.04) while subjects with aMCI had a propensity for increased NFTs in parietal and temporal lobes (p values = 0.07). After adjusting for age at death, the only significant difference was greater densities of temporal lobe NFTs within the aMCI group. Other regional pathology scores for plaques, NFTs, and LBs were similar between groups. Subjects met clinico-pathological criteria for co-existent PD in 24 % aMCI and 47 % naMCI while neuropathological criteria for AD were met in equal percentages of aMCI and of naMCI cases (53 %); these proportional differences were not significant (p values > 0.35). Furthermore, regardless of amnestic status, there was a greater presence of CAA (71 % of MCI with executive dysfunction vs. 39 % without p = 0.03) and a greater presence of CWMR (81 % of MCI with executive dysfunction and 54 % without p = 0.046) in MCI cases with executive dysfunction.


CONCLUSIONS
No single pathologic entity strongly dichotomized MCI groups, perhaps due to the pathologic heterogeneity found within both entities. However, these data suggest the possibility for naMCI to have a propensity for increased LBs and aMCI for increased NFTs in select anatomic regions.
Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, 10515 W. Santa Fe Dr., Sun City, AZ, 85351, USA. Brittany.dugger@bannerhealth.com.
Brittany N
BN
Dugger
The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, AZ, USA. Kathryn.davis@bannerhealth.com.
Kathryn
K
Davis
The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, AZ, USA. michael.ahmadi@bannerhealth.com.
Michael
M
Malek-Ahmadi
Mayo Clinic, Scottsdale, AZ, USA. hentz.joseph@mayo.edu.
Joseph G
JG
Hentz
The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, AZ, USA. shawns1330@gmail.com.
Shawn
S
Sandhu
Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, 10515 W. Santa Fe Dr., Sun City, AZ, 85351, USA. Thomas.beach@bannerhealth.com.
Thomas G
TG
Beach
Mayo Clinic, Scottsdale, AZ, USA. cadler@mayo.edu.
Charles H
CH
Adler
Mayo Clinic, Scottsdale, AZ, USA. Caselli.richard@mayo.edu.
Richard J
RJ
Caselli
Mayo Clinic, Scottsdale, AZ, USA. Johnson.travis2@mayo.edu.
Travis A
TA
Johnson
Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, 10515 W. Santa Fe Dr., Sun City, AZ, 85351, USA. Geidy.serrano@bannerhealth.com.
Geidy E
GE
Serrano
The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, AZ, USA. holly.shill@bannerhealth.com.
Holly A
HA
Shill
The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, AZ, USA. Christine.belden@bannerhealth.com.
Christine
C
Belden
Mayo Clinic, Scottsdale, AZ, USA. DriverDunckley.erika@mayo.edu.
Erika
E
Driver-Dunckley
Mayo Clinic, Scottsdale, AZ, USA. jcaviness@mayo.edu.
John N
JN
Caviness
Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, 10515 W. Santa Fe Dr., Sun City, AZ, 85351, USA. lucia.sue@bannerhealth.com.
Lucia I
LI
Sue
The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, AZ, USA. sandrajacobson@email.arizona.edu.
Sandra
S
Jacobson
The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, AZ, USA. jessica.powell@bannerhealth.com.
Jessica
J
Powell
The Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, AZ, USA. Marwan.sabbagh@bannerhealth.com.
Marwan N
MN
Sabbagh
D000368:Aged; D000369:Aged, 80 and over; D000647:Amnesia / Q000150:complications / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000473:pathology; D002544:Cerebral Infarction / Q000150:complications / Q000473:pathology; D060825:Cognitive Dysfunction / Q000150:complications / Q000473:pathology*; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000150:complications / Q000473:pathology; D016631:Lewy Bodies / Q000473:pathology*; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology*; D010300:Parkinson Disease / Q000150:complications / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology