Larger Hippocampal Volume Linked to Preserved Cognitive Function

Caroline Cassels

April 16, 2008

April 16, 2008 (Chicago, Illinois) — New research presented here at the American Academy of Neurology 60th Annual Meeting suggests larger hippocampal volumes may preserve cognitive function in individuals with high burdens of pathological changes typical of Alzheimer's disease (AD).

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"We know from earlier studies there are some elderly individuals who, despite having a high burden of plaques and tangles, die with very sharp minds, but we don't know why these people are resistant to dementia," study author Deniz Erten-Lyons, MD, from the Oregon Health & Science University, in Portland, told Medscape Neurology & Neurosurgery.

To investigate this phenomenon, Dr. Lyons and colleagues compared cognitively intact subjects who, at autopsy, had high AD pathological burden with individuals with a clinical diagnosis of dementia and a similar AD pathology burden at autopsy.

Using data from the National Institute on Aging and AD Center autopsy series of 477 research volunteers who donated their brains, the investigators selected individuals with no memory or thinking problems 1 year prior to death. In addition, they selected subjects who had been diagnosed with possible or probable AD.

Total brain volume and hippocampal volume were assessed using magnetic resonance imaging (MRI) prior to death. Braak staging for neurofibrillary tangles and Consortium to Establish a Registry for Alzheimer's Disease (CERAD) standards for neuritic plaque scores were used to assess AD pathology at autopsy.

Investigators ended up with a total of 24 patients with clinical AD and 12 cognitively intact individuals, all of whom had similar burdens of disease pathology. They then compared demographic data, including sex distribution, age, education, and socioeconomic status.

Mechanism Unclear

There were no significant differences in demographics between the 2 groups. In terms of absolute numbers, the cognitively intact group had slightly more years of education than the AD group, but this did not reach statistical significance. However, Dr. Erten-Lyons added that if the study sample size had been larger, cognitive reserve may have been a factor.

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When MRI data were compared, total brain and hippocampal volumes in the cognitively intact group were approximately 10% greater.

While it is not clear why a larger hippocampus maybe protective, Dr. Erten-Lyons said 1 possible explanation may be that the cognitively intact individuals started out with larger brains and therefore require a greater burden of plaques and tangles before they reach a threshold that causes them to become symptomatic.

Another possible explanation, she said, is that these individuals are somehow resistant — possibly through genetics — to brain volume and neuronal loss.

"Our study and other previous research emphasize the importance of looking for other mechanisms for dementia. There's a lot of focus on looking at amyloid plaques as a preventive and therapeutic target. I think that our study emphasizes the importance of exploring other mechanisms in dementia that may lead to a better understanding of them, which ultimately could result in new therapeutic and preventive targets," she said.

The study was supported by the Department of Veterans Affairs and the National Institutes of Health.

American Academy of Neurology 60th Annual Meeting: Abstract S01.003. Presented April 15, 2008.


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