Neurology -- Correspondence for Wilson et al., 61 (11) 1479-1485

Correspondence published:

Reply to Kelly et al: Robert S. Wilson, David A. Bennett (4 March 2004)

Proneness to psychological distress is associated with risk of Alzheimer’s disease: James P. Kelly, Christopher M. Filley (4 March 2004)

Reply to Kelly et al 4 March 2004

Robert S. Wilson,
Rush Alzheimer's Disease Center
Rush University Med. Ctr., Armour Academic Ctr., 600 S. Paulina, Suite 2038, Chicago, IL 60612,
David A. Bennett
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Re: Reply to Kelly et al

rwilson{at}rush.edu Robert S. Wilson, et al.

We thank Kelly et al for their interest in our paper. [1]. We agree that the data suggest that psychological distress is associated with a syndrome that resembles AD but does not correspond to its pathological manifestations. The dissociation, which we have also observed for depressive symptoms [5], suggests that chronic psychological distress may be associated with its own distinctive pathology.
Years of research in animal models of chronic stress have identified a spectrum of changes in the hippocampus and related limbic regions (i.e., amygdala, anterior cingulate gyrus) that regulate both stress-related behavior and memory. These changes include dendritic atrophy, neuronal atrophy and decreased neurogenesis, and alterations in the density of stress hormone receptors. On a behavioral level, animals exposed to chronic stress are impaired in hippocoampally-mediated forms of learning and memory. [6] We found that psychological stress was strongly related to decline in episodic memory but not to decline in other forms of thinking and memory. [1] We agree that this selective association between distress and episodic memory, which we have observed with other measures of distress [7] and in other data sets [8], is particularly intriguing because it corresponds so closely to animal models of chronic stress.
This association between psychological distress and memory loss and dementia in old age is important for several reasons. First, it suggests that a trait which we all possess to a greater or lesser degree is associated with dementia. Second, animal research suggests that the neurotoxic effects of stress on the brain may be preventable. Third, it is possible that other risk factors for dementia in old age may work in part by affecting chronic stress or its impact on the brain.
We agree that further research is needed to confirm the association and to elucidate the neurobiological mechanisms underlying it.
References
5.Wilson RS, Barnes LL, Mendes de Leon CF, et al. Depressive symptoms, cognitive decline, and risk of AD in older persons. Neurology 2002;59:364-370.
6. McEwen BS. Effects of adverse experiences for brain structure and function. Biol Psychiatry 2000;48:721-731.
7.Wilson RS, Schneider JA, Bienias JL, Arnold SE, Evans DA, Bennett DA. Depressive symptoms, clinical AD, and cortical plaques and tangles in older persons. Neurology 2003;61:1102-1107.
8.Wilson RS, Fleischman DA, Myers RA, et al. Premorbid proneness to distress and episodic memory impairment in AD. J Neurol Neurosurg Psychiatry, 2004;75:191-195.

Proneness to psychological distress is associated with risk of Alzheimer’s disease 4 March 2004

James P. Kelly,
University of Colorado Health Sciences Center
Colorado Bioscience Park Center, 12635 East Montview Blvd., Suite 130, Aurora, CO 80010,
Christopher M. Filley
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Re: Proneness to psychological distress is associated with risk of Alzheimer’s disease

jpk070{at}northwestern.edu James P. Kelly, et al.

We read with interest the study of Wilson et al [1] describing an association between proneness to psychological distress and Alzheimer's disease (AD). Whereas the findings are of interest, the main conclusion of the paper is not supported by the evidence. The data may justify drawing an association between psychological distress and the risk of developing dementia, but they refute the conclusion that the risk of AD is greater, since no association was found in the subgroup of 140 demented persons who were found to have definite AD by standard research criteria. [2] The authors state, "distress proneness was not associated with AD pathology". [1]
It has been reported that the majority of individuals with clinical AD will have neuropathologically proven AD at autopsy [3], but the authors of this study who imply an association between "distress proneness" and AD is premature.
More intriguing to us is the relationship of psychological distress to the authors' findings of selective decline in episodic memory which could support a link between hippocampal damage and chronic stressful experience. [1] The findings of the present study may ultimately contribute to better understanding the frequent clinical observation of memory dysfunction in elderly depressed patients. Whether the memory deficit of depression is related to the development of AD remains unclear.
It is possible that depression and AD, both common problems in aging, are associated by chance. Further investigation, perhaps including physiological markers of stress [4], will be required to determine the complex relationships between psychological distress, depression, dementia and AD.
References
1. Wilson RS, Evans DA, Bienias JL, et al. Proneness to psychological distress is associated with risk of Alzheimer's disease. Neurology 2003;61:1479-1485.
2.McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer's disease: report of the NINDS/ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34(7):939-944.
3. Cummings JL, Vinters HV, Cole GM, Khachaturian ZS. Alzheimer's disease: etiologies, pathophysiology, cognitive reserve, and treatment opportunities. Neurology 1998;51 (Suppl 1):S2-S17.
4. Morgan CA, Wang S, Rasmusson A, et al. Relationship among plasma cortisol, catecholamines, neuropeptide Y, and human performance during exposure to uncontrollable stress. Psychosom Med 2001;63(3):412-422.