14 May 2012

Can your state of mind affect your risk of getting Alzheimer’s disease? Perhaps so. Two new papers in the May Archives of General Psychiatry highlight the contribution of psychological factors to dementia, for good or ill. On the downside, researchers led by Deborah Barnes at the University of California, San Francisco, report that being depressed during midlife increases the risk of getting dementia, particularly vascular dementia, in old age. More positively, people who have a strong sense of purpose in life can better resist the cognitive effects of AD pathology compared to less driven peers, report researchers led by Patricia Boyle at Rush University, Chicago, Illinois. “What these papers are showing us is that psychological factors are important determinants of aging and may well deserve additional [research] focus,” Boyle noted. For example, other studies have fingered psychological stress as a contributor to dementia (see ARF related news story), and a range of positive personality traits has been associated with healthy aging (see, e.g., Gilhooly et al., 2007).

The literature on depression is somewhat mixed. While a number of studies and a meta-analysis found that it increases the risk for dementia by about twofold (see Ownby et al., 2006; Saczynski et al., 2010; Dotson et al., 2010), whether depression predisposes someone to dementia, or is merely an early symptom of it (see, e.g., ARF related news story and ARF news story) remains controversial. In addition, previous studies have not attempted to tease out how depression contributes to AD versus vascular dementia.

To clarify these issues, Barnes and colleagues examined 45 years of longitudinal data from more than 13,000 people enrolled in the Kaiser Permanente Medical Care Program in northern California. People who were depressed during midlife (in their forties or early fifties) and those depressed during late life (their seventies) both stood an increased risk of developing dementia in their eighties compared to people who had never been depressed. When the authors looked specifically at people with a neurologist’s diagnosis of AD or vascular dementia, they found that late-life depression doubled the risk for AD, but only increased vascular dementia risk by 50 percent. People who were depressed at both midlife and late-life also had twice the risk for AD, but vascular dementia risk zoomed to three times that of the non-depressed. Taken together, the data imply that most of the AD risk comes from late-life depression, while midlife depression primarily contributes to vascular dementia, the authors suggest. Late-life depression may be part of the prodromal phase of AD, and therefore a warning sign, Barnes speculated, while midlife depression could be a true risk factor. “Depression should not be ignored at any age,” she noted. If the finding holds up, it may help reconcile the conflicting results of previous studies, as well as confirm other data showing a link between depression, and vascular disease and dementia (see, e.g., Alexopoulos, 2003).

“The data are quite suggestive that there are two processes going on,” agreed Ray Ownby at Nova Southeastern University, Fort Lauderdale, Florida. One limitation he noted is that vascular dementia often comes mixed with AD, so it is hard to separate the two based solely on a neurologist’s diagnosis. Barnes concurred, and suggested that one way to explore whether vascular issues actually drive dementia will be to add structural MRI data, which reveals blood vessel lesions. Barnes also plans to examine whether treating depression makes a difference in the outcome, which would have large public health implications. The Kaiser database includes medication data, but it is complicated to analyze, Barnes noted. For example, people who receive treatment typically have more severe depression, which could muddy the results.

If depression can push a brain toward dementia, what might protect it? The second paper focuses on “purpose in life,” which is a psychological term that describes people’s tendency to find meaning in their lives and have strong goals. This measure has been associated with better physical health in a number of cross-sectional studies (see, e.g., Ryff et al., 2004). Boyle and colleagues previously showed that high purpose in life is linked to a lowered risk of dementia and a slower rate of cognitive decline (see Boyle et al., 2010).

To try to get at the mechanisms behind this protective effect, Boyle and colleagues examined donated brains from nearly 250 non-demented participants in the Rush Memory and Aging Project who died at an average age of 88. At this age, most people’s brains contain AD pathology, which the authors scored by counting amyloid plaques and neurofibrillary tangles. They found that in people with a similar pathological burden, those who had a higher sense of purpose in life performed better on a set of 19 cognitive tests than those with a low sense of purpose did. In other words, people who scored high in this trait better tolerated gunked-up brains, showing a 30 percent slower rate of cognitive decline over several years compared to peers with less sense of purpose, Boyle told Alzforum. Another way to put it is that those with more sense of purpose tested two or three years “younger” cognitively. The authors also looked separately at amyloid-β and tau pathology, finding that purpose in life interacted only with the latter to modify cognitive score. Tau tangles are more closely linked to cognition than are amyloid plaques, the authors note, which may explain this finding (see Giannakopoulos et al., 2003).

Many researchers have advanced the idea of cognitive reserve to explain why some people better resist the effects of AD pathology than others do. Factors such as education and social engagement are believed to contribute to this reserve (see ARF related news story and ARF news story). The purpose-in-life data, however, remained significant even after correcting for several possible confounders, including education level, social network size, and depression. The data suggest that psychological factors such as purpose in life might be an independent component, Boyle said. The mechanism is not clear, although Boyle speculated that people with high purpose in life might have more efficient neural systems, or be able to recruit additional brain regions to compensate for pathology in regions choked with tau. Boyle plans to use biochemical studies, and structural and functional MRI, to see if there are quantifiable brain correlates. She is also looking more broadly at psychological well-being to try to understand how it promotes physical health. “This work is encouraging in that it suggests there are positive things we can do to help us age well,” she told Alzforum.

Although there are no proven methods to strengthen one’s sense of purpose in life, Ownby suggested that a wide range of activities might promote this trait in the elderly: for example, taking classes at a university, getting involved with younger people, or volunteering for a cause. A recent study in older adults at risk for cognitive impairment showed that volunteer work increased their brain activity in key regions (see Carlson et al., 2009). Lifestyle factors such as exercise have been shown to improve cognition as well (see ARF related news story).—Madolyn Bowman Rogers

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References

News Citations

1. Stress and AD: Does One Beget the Other? 20 Dec 2011
2. Dementia—Stoked by Depression or Simply Depressing? 17 Feb 2006
3. Depression Symptoms May Reflect Alzheimer's Pathology 22 Nov 2002
4. Active Life of Leisure Appears to Build Reserves Against AD 22 Nov 2002
5. Dementia and Education—What You Don’t Know May Speak Volumes 19 Jan 2008
6. Research Brief: Total Activity, Not Just Exercise, Keeps Mind Sharp 8 May 2012

Paper Citations

1. Gilhooly M, Hanlon P, Cullen B, Macdonald S, Whyte B. Successful ageing in an area of deprivation: part 2--a quantitative exploration of the role of personality and beliefs in good health in old age. Public Health. 2007 Nov;121(11):814-21. PubMed.
2. Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry. 2006 May;63(5):530-8. PubMed.
3. Saczynski JS, Beiser A, Seshadri S, Auerbach S, Wolf PA, Au R. Depressive symptoms and risk of dementia: the Framingham Heart Study. Neurology. 2010 Jul 6;75(1):35-41. PubMed.
4. Dotson VM, Beydoun MA, Zonderman AB. Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment. Neurology. 2010 Jul 6;75(1):27-34. PubMed.
5. Alexopoulos GS. Vascular disease, depression, and dementia. J Am Geriatr Soc. 2003 Aug;51(8):1178-80. PubMed.
6. Ryff CD, Singer BH, Dienberg Love G. Positive health: connecting well-being with biology. Philos Trans R Soc Lond B Biol Sci. 2004 Sep 29;359(1449):1383-94. PubMed.
7. Boyle PA, Buchman AS, Barnes LL, Bennett DA. Effect of a purpose in life on risk of incident Alzheimer disease and mild cognitive impairment in community-dwelling older persons. Arch Gen Psychiatry. 2010 Mar;67(3):304-10. PubMed.
8. Giannakopoulos P, Herrmann FR, Bussière T, Bouras C, Kövari E, Perl DP, Morrison JH, Gold G, Hof PR. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology. 2003 May 13;60(9):1495-500. PubMed.
9. Carlson MC, Erickson KI, Kramer AF, Voss MW, Bolea N, Mielke M, McGill S, Rebok GW, Seeman T, Fried LP. Evidence for neurocognitive plasticity in at-risk older adults: the experience corps program. J Gerontol A Biol Sci Med Sci. 2009 Dec;64(12):1275-82. PubMed.

Further Reading

News

1. Dementia—Stoked by Depression or Simply Depressing? 17 Feb 2006
2. Depression Symptoms May Reflect Alzheimer's Pathology 22 Nov 2002
3. Active Life of Leisure Appears to Build Reserves Against AD 22 Nov 2002
4. Dementia and Education—What You Don’t Know May Speak Volumes 19 Jan 2008
5. Research Brief: Total Activity, Not Just Exercise, Keeps Mind Sharp 8 May 2012
6. Stress and AD: Does One Beget the Other? 20 Dec 2011