Depression & Cognition

Previous research has indicated that about a quarter of older adults who become mildly depressed will go on to become seriously depressed within a year or two. A study comparing problem-solving therapy for primary care — a seven-step approach delivered by non-mental-health professionals to help patients resolve difficulties and thus improve coping skills and confidence — with a program of dietary coaching (same number of sessions and hours), has found that elderly adults with mild symptoms of depression responded equally well to both treatments.

The study involved 244 participants, of whom 90 were African-American. Only 9% of people in each intervention went on to experience an episode of major depression, and they all had a similar reduction in depressive symptoms over the two-year study period. Both approaches were equally successful among black and white participants.

The benefit of both programs is assumed to lie in the way they give people greater perceived control over their lives.

http://www.eurekalert.org/pub_releases/2014-03/uops-lic032014.php

Problems with myelin — demyelination (seen most dramatically in MS, but also in other forms of neurodegeneration, including normal aging and depression); failure to develop sufficient myelin (in children and adolescents) — are increasingly being implicated in a wide range of disorders. A new animal study adds to that evidence by showing that social isolation brings about both depression and loss of myelin.

In the study, adult mice were isolated for eight weeks (which is of course longer for a mouse than it is to us) to induce a depressive-like state. They were then introduced to a mouse they hadn’t seen before. Although typically very social animals, those who had been socially isolated didn’t show any interest in interacting with the new mouse — a common pattern in human behavior as well.

Analysis of their brains revealed significantly lower levels of gene transcription for oligodendrocyte cells (the components of myelin) in the prefrontal cortex. This appeared to be caused by a lower production of heterochromatin (tightly packed DNA) in the cell nuclei, producing less mature oligodendrocytes.

Interestingly, even short periods of isolation were sufficient to produce changes in chromatin and myelin, although behavior wasn’t affected.

Happily, however, regardless of length of isolation, myelin production went back to normal after a period of social integration.

The findings add to the evidence that environmental factors can have significant effects on brain development and function, and support the idea that socializing is good for the brain.

Sometime ago, I reported on a study showing that older adults could improve their memory for a future task (remembering to regularly test their blood sugar) by picturing themselves going through the process. Imagination has been shown to be a useful strategy in improving memory (and also motor skills). A new study extends and confirms previous findings, by testing free recall and comparing self-imagination to more traditional strategies.

The study involved 15 patients with acquired brain injury who had impaired memory and 15 healthy controls. Participants memorized five lists of 24 adjectives that described personality traits, using a different strategy for each list. The five strategies were:

  • think of a word that rhymes with the trait (baseline),
  • think of a definition for the trait (semantic elaboration),
  • think about how the trait describes you (semantic self-referential processing),
  • think of a time when you acted out the trait (episodic self-referential processing), or
  • imagine acting out the trait (self-imagining).

For both groups, self-imagination produced the highest rates of free recall of the list (an average of 9.3 for the memory-impaired, compared to 3.2 using the baseline strategy; 8.1 vs 3.2 for the controls — note that the controls were given all 24 items in one list, while the memory-impaired were given 4 lists of 6 items).

Additionally, those with impaired memory did better using semantic self-referential processing than episodic self-referential processing (7.3 vs 5.7). In contrast, the controls did much the same in both conditions. This adds to the evidence that patients with brain injury often have a particular problem with episodic memory (knowledge about specific events). Episodic memory is also particularly affected in Alzheimer’s, as well as in normal aging and depression.

It’s also worth noting that all the strategies that involved the self were more effective than the two strategies that didn’t, for both groups (also, semantic elaboration was better than the baseline strategy).

The researchers suggest self-imagination (and semantic self-referential processing) might be of particular benefit for memory-impaired patients, by encouraging them to use information they can more easily access (information about their own personality traits, identity roles, and lifetime periods — what is termed the self-schema), and that future research should explore ways in which self-imagination could be used to support everyday memory tasks, such as learning new skills and remembering recent events.

We know that people with depression tend to focus on, and remember, negative memories rather than positive. Interestingly, it’s not simply an emotion effect. People with depression, and even those at risk of depression (including those who have had depression), tend to have trouble remembering specific autobiographical memories. That is, memories of events that happened to them at a specific place and time (as opposed to those generalized event memories we construct from similar events, such as the ‘going to the dentist’ memory).

This cognitive difficulty seems to exacerbate their depression, probably through its effect on social encounters and relationships.

A new study, however, has found that a particular training program (“Memory Specificity Training”) can help both their memory for specific events and their symptoms of depression.

The study involved 23 adolescent Afghani refugees in Iran, all of whom had lost their fathers in the war in Afghanistan and who showed symptoms of depression. Half were randomly assigned to the five-week memory training program and half received no training.

The training program involved a weekly 80-minute group session, in which participants learned about different types of memory and memory recall, and practiced recalling specific memories after being given positive, neutral, and negative keywords.

Participants’ memory for specific events was tested at the start of the study, at the end of the five-week training period, and two months after the end of the training. Compared to the control group, those given the training were able to provide more specific memories after the training, and showed fewer symptoms of depression at the two month follow-up (but not immediately after the end of training).

The study follows on from a pilot study in which ten depressed female patients were given four weekly one-hour sessions of memory training. Improvements in memory retrieval were associated with less rumination (dwelling on things), less cognitive avoidance, and improvements in problem-solving skills.

It’s somewhat unfortunate that the control group were given no group sessions, indeed no contact (apart from the tests) of any kind. Nevertheless, and bearing in mind that these are still very small studies, the findings do suggest that it would be helpful to include a component on memory training in any cognitive behavioral therapy for depression.

I have reported previously on research suggesting that rapamycin, a bacterial product first isolated from soil on Easter Island and used to help transplant patients prevent organ rejection, might improve learning and memory. Following on from this research, a new mouse study has extended these findings by adding rapamycin to the diet of healthy mice throughout their life span. Excitingly, it found that cognition was improved in young mice, and abolished normal cognitive decline in older mice.

Anxiety and depressive-like behavior was also reduced, and the mice’s behavior demonstrated that rapamycin was acting like an antidepressant. This effect was found across all ages.

Three "feel-good" neurotransmitters — serotonin, dopamine and norepinephrine — all showed significantly higher levels in the midbrain (but not in the hippocampus). As these neurotransmitters are involved in learning and memory as well as mood, it is suggested that this might be a factor in the improved cognition.

Other recent studies have suggested that rapamycin inhibits a pathway in the brain that interferes with memory formation and facilitates aging.

The study involved 104 healthy older adults (average age 87) participating in the Oregon Brain Aging Study. Analysis of the nutrient biomarkers in their blood revealed that those with diets high in omega 3 fatty acids and in vitamins C, D, E and the B vitamins had higher scores on cognitive tests than people with diets low in those nutrients, while those with diets high in trans fats were more likely to score more poorly on cognitive tests.

These were dose-dependent, with each standard deviation increase in the vitamin BCDE score ssociated with a 0.28 SD increase in global cognitive score, and each SD increase in the trans fat score associated with a 0.30 SD decrease in global cognitive score.

Trans fats are primarily found in packaged, fast, fried and frozen food, baked goods and margarine spreads.

Brain scans of 42 of the participants found that those with diets high in vitamins BCDE and omega 3 fatty acids were also less likely to have the brain shrinkage associated with Alzheimer's, while those with high trans fats were more likely to show such brain atrophy.

Those with higher omega-3 scores also had fewer white matter hyperintensities. However, this association became weaker once depression and hypertension were taken into account.

Overall, the participants had good nutritional status, but 7% were deficient in vitamin B12 (I’m surprised it’s so low, but bear in mind that these are already a select group, being healthy at such an advanced age) and 25% were deficient in vitamin D.

The nutrient biomarkers accounted for 17% of the variation in cognitive performance, while age, education, APOE genotype (presence or absence of the ‘Alzheimer’s gene’), depression and high blood pressure together accounted for 46%. Diet was more important for brain atrophy: here, the nutrient biomarkers accounted for 37% of the variation, while the other factors accounted for 40% (meaning that diet was nearly as important as all these other factors combined!).

The findings add to the growing evidence that diet has a significant role in determining whether or not, and when, you develop Alzheimer’s disease.

In the last five years, three studies have linked lower neighborhood socioeconomic status to lower cognitive function in older adults. Neighborhood has also been linked to self-rated health, cardiovascular disease, and mortality. Such links between health and neighborhood may come about through exposure to pollutants or other environmental stressors, access to alcohol and cigarettes, barriers to physical activity, reduced social support, and reduced access to good health and social services.

Data from the large Women’s Health Initiative Memory Study has now been analyzed to assess whether the relationship between neighborhood socioeconomic status can be explained by various risk and protective factors for poor cognitive function.

Results confirmed that higher neighborhood socioeconomic status was associated with higher cognitive function, even after individual factors such as age, ethnicity, income, education, and marital status have been taken into account. A good deal of this was explained by vascular factors (coronary heart disease, diabetes, stroke, hypertension), health behaviors (amount of alcohol consumed, smoking, physical activity), and psychosocial factors (depression, social support). Nevertheless, the association was still (barely) significant after these factors were taken account of, suggesting some other factors may also be involved. Potential factors include cognitive activity, diet, and access to health services.

In contradiction of earlier research, the association appeared to be stronger among younger women. Consistent with other research, the association was stronger for non-White women.

Data from 7,479 older women (65-81) was included in the analysis. Cognitive function was assessed by the Modified MMSE (3MSE). Neighborhood socioeconomic status was assessed on the basis of: percentage of adults over 25 with less than a high school education, percentage of male unemployment, percentage of households below the poverty line, percentage of households receiving public assistance, percentage of female-headed households with children, and median household income. Around 87% of participants were White, 7% Black, 3% Hispanic, and 3% other. Some 92% had graduated high school, and around 70% had at least some college.

[2523] Shih RA, Ghosh-Dastidar B, Margolis KL, Slaughter ME, Jewell A, Bird CE, Eibner C, Denburg NL, Ockene J, Messina CR, et al. Neighborhood Socioeconomic Status and Cognitive Function in Women. Am J Public Health [Internet]. 2011 ;101(9):1721 - 1728. Available from: http://ajph.aphapublications.org/cgi/content/abstract/101/9/1721

Previous:

Lang IA, Llewellyn DJ, Langa KM, Wallace RB, Huppert FA, Melzer D. 2008. Neighborhood deprivation, individual socioeconomic status, and cognitive function in older people: analyses from the English Longitudinal Study of Ageing. J Am Geriatr Soc., 56(2), 191-198.

Sheffield KM, Peek MK. 2009. Neighborhood context and cognitive decline in older Mexican Americans: results from the Hispanic Established Populations for Epidemiologic Studies of the Elderly. Am J Epidemiol., 169(9), 1092-1101.

Wight RG, Aneshensel CS, Miller-Martinez D, et al. 2006. Urban neighborhood context, educational attainment, and cognitive function among older adults. Am J Epidemiol., 163(12), 1071-1078.

Following several recent studies pointing to the negative effect of air pollution on children’s cognitive performance (see this April 2010 news report and this May 2011 report), a study of public schools in Michigan has found that 62.5% of the 3660 schools in the state are located in areas with high levels of industrial pollution, and those in areas with the highest industrial air pollution levels had the lowest attendance rates and the highest proportions of students who failed to meet state educational testing standards in English and math. Attendance rates are a potential indicator of health levels.

Minority students were especially hit by this — 81.5% of African American and 62.1% of Hispanic students attend schools in the top 10% of the most polluted areas, compared to 44.4% of white students.

Almost all (95%) of the industrial air pollution around schools comes from 12 chemicals (diisocyanates, manganese, sulfuric acid, nickel, chlorine, chromium, trimethylbenzene, hydrochloric acid, molybdenum trioxide, lead, cobalt and glycol ethers) that are all implicated in negative health effects, including increased risk of respiratory, cardiovascular, developmental and neurological disorders, as well as cancer.

There are potentially two issues here: the first is that air pollution causes health issues which lower school attendance and thus impacts academic performance; the other is that the pollution also directly effects the brain, thus affecting cognitive performance.

A new mouse study looking at the effects of air pollution on learning and memory has now found that male mice exposed to polluted air for six hours a day, five days a week for 10 months (nearly half their lifespan), performed significantly more poorly on learning and memory tasks than those male mice living in filtered air. They also showed more signs of anxiety- and depressive-like behaviors.

These changes in behavior and cognition were linked to clear differences in the hippocampus — those exposed to polluted air had fewer dendritic spines in parts of the hippocampus (CA1 and CA3 regions), shorter dendrites and overall reduced cell complexity. Previous mouse research has also found that such pollution causes widespread inflammation in the body, and can be linked to high blood pressure, diabetes and obesity. In the present study, the same low-grade inflammation was found in the hippocampus. The hippocampus is particularly sensitive to damage caused by inflammation.

The level of pollution the mice were exposed to was equivalent to what people may be exposed to in some polluted urban areas.

A review of 35 studies published between 1991 and 2007 has found that depression does not always lead to cognitive impairment. Part of the variability in findings may be due to inconsistent measurement and diagnosis of depression. Processing speed was found to be the cognitive function most consistently affected by depression. Processing speed deficits can be helped by decreasing the amount of information to process at one time.

Amnestic mild cognitive impairment often leads to Alzheimer's disease, but what predicts aMCI? A study involving 94 older adults has revealed that lower performance on tests measuring learning, in conjunction with either slower visuomotor processing speed or depressive symptoms, predicted the development of aMCI a year later with an accuracy of 80-100%. It is worth emphasizing that poor learning alone was not predictive in that time-frame, although one learning measure was predictive of aMCI two years later. Interestingly, neither gender nor possession of the ‘Alzheimer’s gene’ —long believed to be risk factors for mild cognitive impairment — had any substantial influence on later impairment.

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

Psychological distress, not depression, linked to increased risk of stroke

A study following 20,627 people for an average of 8.5 years has found that psychological distress was associated with an increased risk of stroke and that the risk of stroke increased the more distress the participants reported. This association remained the same regardless of cigarette smoking, systolic blood pressure, overall blood cholesterol, obesity, previous heart attack, diabetes, social class, education, high blood pressure treatment, family history of stroke and recent antidepressant medication use. However, there was no increased risk for people who had experienced an episode of major depression in the past year or at any point in their lifetime.

[1298] Surtees PG, Wainwright NWJ, Luben RN, Wareham NJ, Bingham SA, Khaw K-T. Psychological distress, major depressive disorder, and risk of stroke. Neurology [Internet]. 2008 ;70(10):788 - 794. Available from: http://www.neurology.org/cgi/content/abstract/70/10/788

http://www.eurekalert.org/pub_releases/2008-03/aaon-pdn022608.php

Depression increases risk of executive dysfunction in older people

A two-year study of more than 700 older adults (65 and older) has found that depression increased the risk of declining executive function (high-level mental processes, such a making decisions, organizing, planning and doing a series of things in sequence).

[1417] Cui X, Lyness JM, Tu X, King DA, Caine ED. Does Depression Precede or Follow Executive Dysfunction? Outcomes in Older Primary Care Patients. Am J Psychiatry [Internet]. 2007 ;164(8):1221 - 1228. Available from: http://ajp.psychiatryonline.org/cgi/content/abstract/164/8/1221

http://www.eurekalert.org/pub_releases/2007-10/uorm-dcf100807.php

Depressed older adults more likely to become cognitively impaired

A study involving 2,220 participants in the Cardiovascular Health Study, a longitudinal prospective study of adults 65 and older, has found that 19.7% of subjects with moderate to high depression developed mild cognitive impairment within six years, compared to 10% of subjects with no depressive symptoms and 13.3% of subjects with low depressive symptoms. There was no correlation between depression and vascular disease, although it has been hypothesized that vascular disease might lead to both depression and cognitive impairment by causing inadequate blood flow to different brain structures.

[409] Barnes DE, Alexopoulos GS, Lopez OL, Williamson JD, Yaffe K. Depressive Symptoms, Vascular Disease, and Mild Cognitive Impairment: Findings From the Cardiovascular Health Study. Arch Gen Psychiatry [Internet]. 2006 ;63(3):273 - 279. Available from: http://archpsyc.ama-assn.org/cgi/content/abstract/63/3/273

http://www.eurekalert.org/pub_releases/2006-03/uoc--doa030206.php

Treatable depression often accompanies mild memory loss

A large-scale study of older adults begun in 1989 has revealed that 43% of those with mild cognitive impairment had psychiatric symptoms (such as depression, irritability, loss of interest in activities, or changes in sleep or appetite) in the month before examination. Such symptoms are often shrugged off as emotional reactions to memory decline, but they may be due to changes in brain function, and may respond to treatment.

[1275] Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S. Prevalence of Neuropsychiatric Symptoms in Dementia and Mild Cognitive Impairment: Results From the Cardiovascular Health Study. JAMA [Internet]. 2002 ;288(12):1475 - 1483. Available from: http://jama.ama-assn.org/cgi/content/abstract/288/12/1475

http://www.eurekalert.org/pub_releases/2002-09/wfub-tdo092702.php