TY - JOUR
T1 - Resistance to Alzheimer disease neuropathologic changes and apparent cognitive resilience in the Nun and Honolulu-Asia Aging Studies
AU - Latimer, Caitlin S.
AU - Keene, C. Dirk
AU - Flanagan, Margaret E.
AU - Hemmy, Laura S.
AU - Lim, Kelvin O.
AU - White, Lon R.
AU - Montine, Kathleen S.
AU - Montine, Thomas J.
N1 - Funding Information:
The authors would like to thank Allison Beller, Natalie Coleman, Kim Howard, and Aimee Schantz for administrative and technical assistance; the School Sisters of Notre Dame and men of the HAAS for their generous participation in these studies; and the late Dr. William Markesbery for his contributions to both studies and to the field of neuropathology.
Publisher Copyright:
© 2017 American Association of Neuropathologists, Inc.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Two population-based studies key to advancing knowledge of brain aging are the Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their neuropathologic data allows cross comparison, with findings common to both studies likely generalizable, while distinct observations may point to aging brain changes that are dependent on sex, ethnicity, environment, or lifestyle factors. Here, we expanded the neuropathologic evaluation of these 2 studies using revised NIA-Alzheimer's Association guidelines and compared directly the neuropathologic features of resistance and apparent cognitive resilience. There were significant differences in prevalence of Alzheimer disease neuropathologic change, small vessel vascular brain injury, and Lewy body disease between these 2 studies, suggesting that sex, ethnicity, and lifestyle factors may significantly influence resistance to developing brain injury with age. In contrast, hippocampal sclerosis prevalence was very similar, but skewed to poorer cognitive performance, suggesting that hippocampal sclerosis could act sequentially with other diseases to impair cognitive function. Strikingly, despite these observed differences, the proportion of individuals resistant to all 4 diseases of brain or displaying apparent cognitive resilience was virtually identical between HAAS and Nun Study participants. Future in vivo validation of these results awaits comprehensive biomarkers of these 4 brain diseases.
AB - Two population-based studies key to advancing knowledge of brain aging are the Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their neuropathologic data allows cross comparison, with findings common to both studies likely generalizable, while distinct observations may point to aging brain changes that are dependent on sex, ethnicity, environment, or lifestyle factors. Here, we expanded the neuropathologic evaluation of these 2 studies using revised NIA-Alzheimer's Association guidelines and compared directly the neuropathologic features of resistance and apparent cognitive resilience. There were significant differences in prevalence of Alzheimer disease neuropathologic change, small vessel vascular brain injury, and Lewy body disease between these 2 studies, suggesting that sex, ethnicity, and lifestyle factors may significantly influence resistance to developing brain injury with age. In contrast, hippocampal sclerosis prevalence was very similar, but skewed to poorer cognitive performance, suggesting that hippocampal sclerosis could act sequentially with other diseases to impair cognitive function. Strikingly, despite these observed differences, the proportion of individuals resistant to all 4 diseases of brain or displaying apparent cognitive resilience was virtually identical between HAAS and Nun Study participants. Future in vivo validation of these results awaits comprehensive biomarkers of these 4 brain diseases.
KW - Alzheimer disease neuropathologic change
KW - Cognitive resilience
KW - NIA-AA guidelines
KW - Population-based cohort
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U2 - 10.1093/jnen/nlx030
DO - 10.1093/jnen/nlx030
M3 - Article
C2 - 28499012
AN - SCOPUS:85019642567
SN - 0022-3069
VL - 76
SP - 458
EP - 466
JO - Journal of neuropathology and experimental neurology
JF - Journal of neuropathology and experimental neurology
IS - 6
ER -