Factors associated with resistance to dementia despite high Alzheimer disease pathology

  • International

2nd February 2009, American Academy of Neurology

D. Erten-Lyons, MD, R. L. Woltjer, MD, H. Dodge, PhD, R. Nixon, MD, R. Vorobik, BA, J. F. Calvert, MD, M. Leahy, RN, T. Montine, MD and J. Kaye, MD

Background: Autopsy series have shown that some elderly peopleremain with normal cognitive function during life despite havinghigh burdens of pathologic lesions associated with Alzheimerdisease (AD) at death. Understanding why these individuals showno cognitive decline, despite high AD pathologic burdens, maybe key to discovery of neuroprotective mechanisms.

Methods: A total of 36 subjects who on autopsy had Braak stageV or VI and moderate or frequent neuritic plaque scores basedon Consortium to Establish a Registry for Alzheimer's Disease(CERAD) standards were included. Twelve had normal cognitivefunction and 24 a diagnosis of AD before death. Demographiccharacteristics, clinical and pathologic data, as well as antemortembrain volumes were compared between the groups.

Results: In multiple regression analysis, antemortem hippocampaland total brain volumes were significantly larger in the groupwith normal cognitive function after adjusting for gender, ageat MRI, time from MRI to death, Braak stage, CERAD neuriticplaque score, and overall presence of vascular disease.

Conclusion: Larger brain and hippocampal volumes were associatedwith preserved cognitive function during life despite a highburden of Alzheimer disease (AD) pathologic lesions at death.A better understanding of processes that lead to preservationof brain volume may provide important clues for the discoveryof mechanisms that protect the elderly from AD.