Alzheimer's & Depression

Depression, stress, & distress as risk factors for Alzheimer's

See also

Depression (as a factor in general cognitive & memory problems)

A study that followed 800 Swedish middle-aged women from 1968 to 2005 has found that high levels of stress in middle age increased Alzheimer’s risk by 21% and risk of any dementia by 15%.

Of the 800 women, 425 died during the course of the study while 153 (19%) developed dementia (of whom 104 developed Alzheimer’s), at an average age of 78. The number of stressors and long-standing distress were independently associated with Alzheimer’s.

The finding doesn’t tell us whether stress is contributing to the development of dementia, or whether it is simply an indicator of another underlying risk factor.

http://www.theguardian.com/society/2013/sep/30/stress-middle-age-women-dementia

The open access paper is available at http://bmjopen.bmj.com/content/3/9/e003142.abstract.

A study, involving 371 patients with mild cognitive impairment, has found that those with depressive symptoms had higher levels of amyloid-beta, particularly in the frontal cortex and the anterior and posterior cingulate gyrus (both involved in mood disorders such as depression).

The findings suggest that late-life depression could be a major risk factor for developing Alzheimer's faster than others.

http://www.eurekalert.org/pub_releases/2014-06/sonm-dit060814.php

Brendel, M. et al. 2014. Subsyndromal late life depression is associated with amyloid accumulation in mild cognitive impairment. Presented at the Society of Nuclear Medicine and Molecular Imaging's 2014 Annual Meeting, June 7, 2014, St. Louis, Missouri.

Late-life depression is associated with an increased risk for all-cause dementia, Alzheimer’s disease, and, most predominantly, vascular dementia, a new study shows.

A new meta-analysis extends previous research showing a link between depression and Alzheimer’s disease to late-life depression and dementia. The analysis of 23 studies concluded that those with late-life depression were significantly more likely to develop dementia (1.85 times more likely), and that the risk of developing vascular dementia was significantly greater than that of developing Alzheimer’s (2.52 vs 1.65).

Late-life depression is estimated to affect 15% of older adults (65+) in the U.S. It has been associated to social isolation, as well as poorer health.

Interestingly, another recent study has explored the difficulties of disentangling major depression and early Alzheimer’s in older adults, given the overlap in symptoms. The study, involving 120 older depressed patients, found that tests of episodic memory were most predictive of Alzheimer’s (as compared to other cognitive tests, for example, in executive function).

http://www.futurity.org/health-medicine/late-life-depression-may-boost-dementia-risk/ (Press release, 1st study)

http://newoldage.blogs.nytimes.com/2013/05/01/does-depression-contribute-to-dementia/ (Commentary, 1st study)

[3405] Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF. Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. The British Journal of Psychiatry [Internet]. 2013 ;202(5):329 - 335. Available from: http://bjp.rcpsych.org/content/202/5/329

[3408] Rushing NC, Sachs-Ericsson N, Steffens DC. Neuropsychological indicators of preclinical Alzheimer's disease among depressed older adults. Aging, Neuropsychology, and Cognition [Internet]. 0 :1 - 30. Available from: http://www.tandfonline.com/doi/abs/10.1080/13825585.2013.795514

There's quite a bit of evidence now that socializing — having frequent contact with others — helps protect against cognitive impairment in old age. We also know that depression is a risk factor for cognitive impairment and dementia. There have been hints that loneliness might also be a risk factor. But here’s the question: is it being alone, or feeling lonely, that is the danger?

A large Dutch study, following 2173 older adults for three years, suggests that it is the feeling of loneliness that is the main problem.

At the start of the study, some 46% of the participants were living alone, and some 50% were no longer or never married (presumably the discrepancy is because many older adults have a spouse in a care facility). Some 73% said they had no social support, while 20% reported feelings of loneliness.

Those who lived alone were significantly more likely to develop dementia over the three year study period (9.3% compared with 5.6% of those who lived with others). The unmarried were also significantly more likely to develop dementia (9.2% vs 5.3%).

On the other hand, among those without social support, 5.6% developed dementia compared with 11.4% with social support! This seems to contradict everything we know, not to mention the other results of the study, but the answer presumably lies in what is meant by ‘social support’. Social support was assessed by the question: Do you get help from family, neighbours or home support? It doesn’t ask the question of whether help would be there if they needed it. So this is not a question of social networks, but more one of how much you need help. This interpretation is supported by the finding that those receiving social support had more health problems.

So, although the researchers originally counted this question as part of the measure of social isolation, it is clearly a poor reflection of it. Effectively, then, that leaves cohabitation and marriage as the only indices of social isolation, which is obviously inadequate.

However, we still have the interesting question re loneliness. The study found that 13.4% of those who said they felt lonely developed dementia compared with 5.7% of those who didn’t feel this way. This is a greater difference than that found with the ‘socially isolated’ (as measured!). Moreover, once other risk factors, such as age, education, and other health factors, were accounted for, the association between living alone and dementia disappeared, while the association with feelings of loneliness remained.

Of course, this still doesn’t tell us what the association is! It may be that feelings of loneliness simply reflect cognitive changes that precede Alzheimer’s, but it may be that the feelings themselves are decreasing cognitive and social activity. It may also be that those who are prone to such feelings have personality traits that are in themselves risk factors for cognitive impairment.

I would like to see another large study using better metrics of social isolation, but, still, the study is interesting for its distinction between being alone and feeling lonely, and its suggestion that it is the subjective feeling that is more important.

This is not to say there is no value in having people around! For a start, as discussed, the measures of social isolation are clearly inadequate. Moreover, other people play an important role in helping with health issues, which in turn greatly impact cognitive decline.

Although there was a small effect of depression, the relationship between feeling lonely and dementia remained after this was accounted for, indicating that this is a separate factor (on the other hand feelings of loneliness were a risk factor for depression).

A decrease in cognitive score (MMSE) was also significantly greater for those experiencing feelings of loneliness, suggesting that this is also a factor in age-related cognitive decline.

The point is not so much that loneliness is more detrimental than being alone, but that loneliness in itself is a risk factor for cognitive decline and dementia. This suggests that we should develop a better understanding of loneliness, how to identify the vulnerable, and how to help them.

A ten-year study involving 7,239 older adults (65+) has found that each common health complaint increased dementia risk by an average of about 3%, and that these individual risks compounded. Thus, while a healthy older adult had about an 18% chance of developing dementia after 10 years, those with a dozen of these health complaints had, on average, closer to a 40% chance.

It’s important to note that these complaints were not for serious disorders that have been implicated in Alzheimer’s. The researchers constructed a ‘frailty’ index, involving 19 different health and wellbeing factors: overall health, eyesight, hearing, denture fit, arthritis/rheumatism, eye trouble, ear trouble, stomach trouble, kidney trouble, bladder control, bowel control, feet/ankle trouble, stuffy nose/sneezing, bone fractures, chest problems, cough, skin problems, dental problems, other problems.

Not all complaints are created equal. The most common complaint — arthritis/rheumatism —was only slightly higher among those with dementia. Two of the largest differences were poor eyesight (3% of the non-demented group vs 9% of those with dementia) and poor hearing (3% and 6%).

At the end of the study, 4,324 (60%) were still alive, and of these, 416 (9.6%) had Alzheimer's disease, 191 (4.4%) had another sort of dementia and 677 (15.7%) had other cognitive problems (but note that 1,023 were of uncertain cognitive ability).

While these results need to be confirmed in other research — the study used data from broader health surveys that weren’t specifically designed for this purpose, and many of those who died during the study will have probably had dementia — they do suggest the importance of maintaining good general health.

Common irregular heartbeat raises risk of dementia

In another study, which ran from 1994 to 2008 and followed 3,045 older adults (mean age 74 at study start), those with atrial fibrillation were found to have a significantly greater risk of developing Alzheimer’s.

At the beginning of the study, 4.3% of the participants had atrial fibrillation (the most common kind of chronically irregular heartbeat); a further 12.2% developed it during the study. Participants were followed for an average of seven years. Over this time, those with atrial fibrillation had a 40-50% higher risk of developing dementia of any type, including probable Alzheimer's disease. Overall, 18.8% of the participants developed some type of dementia during the course of the study.

While atrial fibrillation is associated with other cardiovascular risk factors and disease, this study shows that atrial fibrillation increases dementia risk more than just through this association. Possible mechanisms for this increased risk include:

  • weakening the heart's pumping ability, leading to less oxygen going to the brain;
  • increasing the chance of tiny blood clots going to the brain, causing small, clinically undetected strokes;
  • a combination of these plus other factors that contribute to dementia such as inflammation.

The next step is to see whether any treatments for atrial fibrillation reduce the risk of developing dementia.

Stress may increase risk for Alzheimer's disease

And a rat study has shown that increased release of stress hormones leads to cognitive impairment and that characteristic of Alzheimer’s disease, tau tangles. The rats were subjected to stress for an hour every day for a month, by such means as overcrowding or being placed on a vibrating platform. These rats developed increased hyperphosphorylation of tau protein in the hippocampus and prefrontal cortex, and these changes were associated with memory deficits and impaired behavioral flexibility.

Previous research has shown that stress leads to that other characteristic of Alzheimer’s disease: the formation of beta-amyloid.

Data from the long-running Framingham Heart Study has revealed that depression significantly increased the risk of developing dementia. Of the 125 people (13%) who were classified as having depression at the start of the study, 21.6% had developed dementia by the end of the study (17 years later). This compares to around 16.6% of those who weren’t depressed. When age, gender, education, homocysteine, and APOE gene status were taken into account, depressed participants had a more than 50% increased risk of developing dementia. Moreover, for each 10-point increase on the self-report scale used to measure depression (CES-D), there was a significant increase in the dementia risk. These findings, from one of the largest and longest population-based studies, should clarify the inconsistent results from earlier research.

There are several possible ways depression might increase the risk of dementia — for example, through the brain inflammation or the increased level of certain proteins that occurs during depression; or through the effects on lifestyle (reduced exercise, social engagement, poor diet).

Both diabetes and clinical depression are known to be risk factors for dementia. Now a study that tracked nearly 4000 diabetics over 5 years has found having both increased the risk 2.7-fold. Nearly 8% of the diabetics with major depression (36 of 455) developed dementia over the five years, compared to 4.8% of those with diabetes alone (163 of 3382). Those who developed dementia within 2 years of being diagnosed with depression were excluded. Depression is common among people who have diabetes.

Older news items (pre-2010) brought over from the old website

Apathy common in dementia patients with white matter changes

A study involving 176 patients with Alzheimer's, vascular dementia or mixed dementia, or mild cognitive impairment, has found that 82% of the patients with changes in their white matter were apathetic, compared to an overall rate of 58%. This discovery suggests that there is a common biological reason behind this apathy, irrespective of which type of dementia a patient has. White matter changes were also associated with age, gender, blood pressure, hypertension, ischaemic heart disease, mental slowness, disinhibition, gait disturbance and focal neurologic symptoms. Apathy, mental slowness and age were the most consistent predicting factors for WMCs.

Jonsson, M., Edman, Å., Lind, K., Rolstad, S., Sjögren, M., & Wallin, A. (2009). Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia. International Journal of Geriatric Psychiatry, 9999(9999), n/a. doi: 10.1002/gps.2379.

http://www.eurekalert.org/pub_releases/2009-12/uog-aci120209.php

Depression may increase risk of Alzheimer's disease in people with memory problems

A three-year study involving 756 people with mild cognitive impairment found increases in depressive symptoms was positively associated with increased risk in developing Alzheimer’s. The study also found that, for those who were depressed, taking the Alzheimer’s drug donepezil significantly reduced the risk of developing Alzheimer’s, compared to those taking vitamin E or placebo. Donepezil had little effect on those who were not depressed.

Lu, P.H. et al. 2009. Donepezil delays progression to AD in MCI subjects with depressive symptoms. Neurology, 72, 2115-2121.

http://www.eurekalert.org/pub_releases/2009-06/aaon-dmi060909.php

Being social and not easily stressed reduces dementia risk

A six-year Swedish study involving 506 older people who did not have dementia when first examined has found that those who scored high in extraversion and low in neuroticism (meaning easily distressed) had the lowest dementia risk. Those people who were not socially active but calm and relaxed had a 50% lower risk of developing dementia compared with people who were isolated and prone to distress. The dementia risk was also 50% lower for people who were outgoing and calm compared to those who were outgoing and prone to distress. However, neither high neuroticism nor low extraversion alone was related to a significantly higher risk of dementia.

Wang, H. -X. et al. 2009. Personality and lifestyle in relation to dementia incidence. Neurology, 72, 253-259.

http://www.eurekalert.org/pub_releases/2009-01/aaon-saa011309.php

Depression a risk factor for Alzheimer's disease

Previous studies have found higher levels of depressive symptoms among patients with Alzheimer’s disease or mild cognitive impairment. Now the Religious Orders Study reveals that although those with more symptoms of depression at the beginning of the study (in 1994) were more likely to develop Alzheimer’s disease, those who developed Alzheimer’s disease showed no increase in depressive symptoms in the years before the diagnosis was made. This suggests that depression is a risk factor for dementia rather than a consequence.

Wilson, R.S., Arnold, S.E., Beck, T.L., Bienias, J.L. & Bennett, D.A. 2008. Change in Depressive Symptoms During the Prodromal Phase of Alzheimer Disease. Archives of General Psychiatry, 65(4), 439-445.

http://www.eurekalert.org/pub_releases/2008-04/jaaj-sod040308.php

High stress and genetic risk factor lead to increased memory decline

A study involving 91 older, healthy subjects (mean age 78.8 years) has found that those low on stress (low levels in cortisol) or without the APOE-ε4 gene performed better on memory measures than those with high stress or those with the APOE-ε4 gene. Those who had the gene and had high stress levels showed the greatest memory impairment.

Peavy, G.M. et al. 2007. The Effects of Prolonged Stress and APOE Genotype on Memory and Cortisol in Older Adults. Biological Psychiatry, 62 (5), 472-478.

http://www.eurekalert.org/pub_releases/2007-08/e-naf082707.php

Distress-prone people more likely to develop memory problems

Data from two large, long-running studies, the Religious Orders Study and the Memory and Aging Project, has revealed that those who most often experience negative emotions such as depression and anxiety (according to self report) were 40% more likely to develop mild cognitive impairment than those who were least prone to negative emotions. This follows on from an earlier study showing that people who are easily distressed are more likely to develop Alzheimer’s disease than more easygoing people.

Wilson, R.S., Schneider, J.A., Boyle, P.A., Arnold, S.E., Tang, Y. & Bennett, D.A. 2007. Chronic distress and incidence of mild cognitive impairment. Neurology, 68, 2085-2092.

http://www.eurekalert.org/pub_releases/2007-06/aaon-dpm060507.php

Loneliness increases risk of Alzheimer's disease

Social isolation has been linked with an increased risk of dementia and cognitive decline, but perceived isolation — feeling alone rather than being alone — hasn’t been investigated. A new four-year study of 823 older adults provides evidence that loneliness is a risk factor for Alzheimer’s. 76 individuals developed Alzheimer’s over the course of the study, and the risk of developing it increased around 51% for each point on the 5-point loneliness score. The findings did not change significantly when the researchers factored in markers of social isolations, such as a small network and infrequent social activities. Autopsies performed on 90 individuals who died during the study show that loneliness is a risk factor rather than an early sign of the disease.

Wilson, R.S., Krueger, K.R., Arnold, S.E., Schneider, J.A., Kelly, J.F., Barnes, L.L., Tang, Y. & Bennett, D.A. 2007. Loneliness and Risk of Alzheimer Disease. Archives of General Psychiatry, 64, 234-240.

http://www.eurekalert.org/pub_releases/2007-02/rumc-law020207.php

Depression associated with changes in the brain in Alzheimer's

A lifetime history of depression is associated with increased plaques and tangles in the brains of those with Alzheimer's disease and more rapid cognitive decline, confirming previous indications that depression may be a risk factor for Alzheimer’s.

Rapp, M.A. et al. 2006. Increased Hippocampal Plaques and Tangles in Patients With Alzheimer Disease With a Lifetime History of Major Depression. Archives of General Psychiatry, 63,161-167.

http://www.eurekalert.org/pub_releases/2006-02/tmsh-ldb020306.php

Distress-prone people more likely to develop Alzheimer's disease

The Religious Orders Study has found that those who most often experience negative emotions like depression and anxiety were twice as likely to develop Alzheimer's disease as those who were least prone to experience negative emotions. A person’s tendency to experience psychological distress has been shown to be a stable personality trait throughout adulthood. Proneness to stress was specifically associated with a decline in episodic memory (measured by asking participants to recall a list of words or a story) — an area particularly problematic for those with Alzheimer's. Episodic memory ability declined 10 times faster in those high in proneness to distress than in those low in this response. This result was not altered when participants’ engagement in cognitively stimulating activities. Examination of the brains of those who have died during the long-term study appears to rule out the possibility that proneness to distress is an early sign of Alzheimer's disease rather than a risk factor, although more research is needed to confirm this.

Wilson, R.S., Evans, D.A., Bienias, J.L., Mendes de Leon, C.F., Schneider, J.A. & Bennett, D.A. 2003. Proneness to psychological distress is associated with risk of Alzheimer’s disease. Neurology, 61, 1479-1485.

http://www.eurekalert.org/pub_releases/2003-12/aaon-pm120203.php

Study points to depression as a risk for developing Alzheimer's disease

More than 650 elderly people took part in a seven-year study which has revealed that those with the greatest number of depressive symptoms at the start of the study were more likely to develop Alzheimer's disease and also showed more rapid cognitive decline.

Wilson, R.S., Barnes, L.L., de Leon, C.F.M., Aggarwal, N.T., Schneider, J.S., Bach, J., Pilat, J., Beckett, L.A., Arnold, S.E., Evans, D.A. & Bennett, D.A. 2002. Depressive symptoms, cognitive decline, and risk of AD in older persons. Neurology, 59, 364-370.

http://www.eurekalert.org/pub_releases/2002-08/aaon-spt080502.php