Diabetes & Cognition

Brain scans of 9,772 people aged 44 to 79, who were enrolled in the UK Biobank study, have revealed that smoking, high blood pressure, high pulse pressure, diabetes, and high BMI — but not high cholesterol — were all linked to greater brain shrinkage, less grey matter and less healthy white matter.

Smoking, high blood pressure, and diabetes were the most important factors, but there was also a compound effect, with the number of vascular risk factors being associated with greater damage to the brain. On average, those with the highest vascular risk had nearly 3% less volume of grey matter, and one-and-a-half times the damage to their white matter, compared to people who had the lowest risk.

The brain regions affected were mainly those involved in ‘higher-order’ thinking, and those known to be affected early in the development of dementia.

The associations were as strong for middle-aged adults as for older ones, suggesting the importance of tackling these factors early.

While the effect size was small, the findings emphasize how vulnerable the brain is to vascular factors even in relatively healthy adults. This also suggests the potential of lifestyle changes for fighting cognitive decline.

Although this study didn't itself examine cognitive performance in its participants, other studies have shown links between cognitive impairment and vascular risk factors, particularly diabetes, obesity, hypertension, and smoking.

https://www.eurekalert.org/pub_releases/2019-03/esoc-shb030719.php

Cognitive decline in type 2 diabetes linked to white matter hyperintensities

While type 2 diabetes has been associated with cognitive problems, the mechanism has been unclear. Now a study involving 93 people with type 2 diabetes has found that greater white matter hyperintensities (indicative of cerebral small vessel disease) were associated with decreased processing speed (but not with memory or executive function).

https://www.eurekalert.org/pub_releases/2018-09/w-rem091818.php

Cox, Simon R. et al. 2019. Associations between vascular risk factors and brain MRI indices in UK Biobank. European Heart Journal. doi:10.1093/eurheartj/ehz100

[4395] Mankovsky, B., Zherdova N., van den Berg E., Biessels G.-J., & de Bresser J.
(2018).  Cognitive functioning and structural brain abnormalities in people with Type 2 diabetes mellitus.
Diabetic Medicine. 35(12), 1663 - 1670.

 

A study involving 65 older adults (average age 66), of whom 35 had type 2 diabetes, has found that after two years, those with diabetes had decreases in their ability to regulate blood flow in the brain, and a reduced ability to regulate blood flow was associated with lower cognitive scores.

Specifically, at the start of the study those with diabetes scored an average 46 points on a cognitive test, compared with 55 in the control group. After two years, the diabetics' scores had fallen to an average of 41, while the scores of the control group hadn't fallen at all.

Greater decreases in blood flow regulation were also associated with higher levels of inflammation.

It's suggested that inflammation impairs blood flow regulation, and this accelerates cognitive decline.

http://www.eurekalert.org/pub_releases/2015-07/aaon-ssl070615.php

Chung, C.-C., Pimentel, D., Jor’dan, A. J., Hao, Y., Milberg, W., & Novak, V. (2015). Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes. Neurology, 85(5), 450–458. http://doi.org/10.1212/WNL.0000000000001820

A German study involving 1,936 older adults (50+) has found that mild cognitive impairment (MCI) occurred twice as often in those diagnosed with type 2 diabetes.

Analysis of 560 participants with MCI (289 with amnestic MCI and 271 with non-amnestic MCI) and 1,376 cognitively normal participants revealed that this was only observed in middle-aged participants (50-65), not in older participants (65-80). Interestingly, there was a gender difference. Middle-aged women showed a stronger association between diabetes and amnestic MCI, while middle-aged men showed a stronger association with non-amnestic MCI.

http://www.eurekalert.org/pub_releases/2014-09/ip-dma090214.php

Winkler, A., Dlugaj, M., Weimar, C., Jöckel, K.-H., Erbel, R., Dragano, N., & Moebus, S. (2014). Association of diabetes mellitus and mild cognitive impairment in middle-aged men and women. Journal of Alzheimer’s Disease: JAD, 42(4), 1269–1277. http://doi.org/10.3233/JAD-140696

A study involving older adults has found that diabetes was associated with higher levels of tau protein and greater brain atrophy.

The study involved 816 older adults (average age 74), of whom 397 had mild cognitive impairment, 191 had Alzheimer's disease, and 228 people had no cognitive problems. Fifteen percent (124) had diabetes.

Those with diabetes had greater levels of tau protein in the spinal and brain fluid regardless of cognitive status. Tau tangles are characteristic of Alzheimer's.

Those with diabetes also had cortical tissue that was an average of 0.03 millimeter less than those who didn't have diabetes, regardless of their cognitive status. This greater brain atrophy in the frontal and parietal cortices may be partly related to the increase in tau protein.

There was no link between diabetes and amyloid-beta, the other main pathological characteristic of Alzheimer's.

Previous research has indicated that people with type 2 diabetes have double the risk of developing dementia. Previous research has also found that those who had been diabetic for longer had a greater degree of brain atrophy

The findings support the idea that type 2 diabetes may have a negative effect on cognition independent of dementia, and that this effect may be driven by an increase in tau phosphorylation.

http://www.eurekalert.org/pub_releases/2015-09/aaon-dab082715.php

A review and a large study have recently added to the growing evidence that type 2 diabetes is not only a risk factor for Alzheimer's, but is also linked to poorer cognitive function and faster age-related cognitive decline. The amount of this also seems to be related to glucose control in a dose-dependent manner.

Somewhat surprisingly, there is evidence that the association is not linked to vascular factors, but is in significant part explained by neuron loss. That part is not surprising — brains 'naturally' shrink with age, and growing evidence points to the importance of exercise (which promotes the growth of new neurons) in combating that loss. If diabetics are less likely to exercise (which seems likely, given the strong association with obesity), this may, at least in part, account for the greater brain atrophy.

Type 2 diabetes linked to poorer executive function

A meta-analysis of 60 studies involving a total of 9815 people with Type 2 diabetes and 69,254 control individuals, has found a small but reliable association between diabetes and poorer executive function. This was true across all aspects of executive function tested: verbal fluency, mental flexibility, inhibition, working memory, and attention.

Unfortunately, effective diabetes management does depend quite heavily on executive function, making this something of a negative feedback cycle.

http://www.eurekalert.org/pub_releases/2015-02/uow-t2d021315.php

Diabetes in midlife linked to greater age-related cognitive decline

A long-running U.S. study involving 13,351 adults, has found that cognitive decline over 19 years was 19% greater among those who had diabetes in midlife. Moreover, cognitive decline increased with higher hemoglobin A1c level and longer duration of diabetes.

At the beginning of the study, participants were aged 48-67 (median: 57), and 13% of participants were diagnosed as diabetic. Cognition was tested using delayed word recall, digit symbol substitution, and word fluency tests.

The findings support the view that glucose control in midlife is important to protect against cognitive decline later in life.

http://www.jwatch.org/na36497/2014/12/31/diabetes-midlife-associated-with-accelerated-cognitive

http://www.sciencedaily.com/releases/2014/12/141201191253.htm

http://www.psychiatryadvisor.com/diabetes-may-accelerate-cognitive-decline/article/386208/

Brain atrophy linked with cognitive decline in diabetes

A 2013 study showed that almost half of the cognitive impairment seen among diabetics was explained by their loss of gray matter.

Brain scans and cognitive tests of 350 people with Type 2 diabetes and 363 people without diabetes revealed that those with diabetes had more cerebral infarcts and greater shrinkage in specific regions of the brain. Diabetes was associated with poorer visuospatial memory, planning, visual memory, and processing speed. These associations were independent of vascular risk factors, cerebrovascular lesions, or white matter volume, but almost half of the associations were explained by the shrinkage of gray matter in the hippocampus and across the brain.

http://www.eurekalert.org/pub_releases/2013-09/mu-bal091113.php

Vincent, C. & Hall, P.A. 2015. Executive Function in Adults With Type 2 Diabetes: A Meta-Analytic Review. Psychosomatic Medicine, doi: 10.1097/PSY.0000000000000103

[3910] Rawlings, A. M., A. Sharrett R., Schneider A. L. C., Coresh J., Albert M., Couper D., et al.
(2014).  Diabetes in midlife and cognitive change over 20 years: a cohort study.
Annals of Internal Medicine. 161(11), 785 - 793.

[3909] Moran, C., Phan T. G., Chen J., Blizzard L., Beare R., Venn A., et al.
(2013).  Brain Atrophy in Type 2 Diabetes Regional distribution and influence on cognition.
Diabetes Care. 36(12), 4036 - 4042.

A study involving 614 patients with type 2 diabetes (mean age 62) has found that longer duration of diabetes was associated with more brain volume loss, particularly in the gray matter. Roughly, for every 10 years of diabetes, the brain was similar to that of a non-diabetic person who was two years older.

However, the study did not confirm any association of diabetes characteristics with small vessel ischemic disease.

http://www.eurekalert.org/pub_releases/2014-04/rson-dda042214.php

I’ve reported before on the growing evidence that metabolic syndrome in middle and old age is linked to greater risk of cognitive impairment in old age and faster decline. A new study shows at least part of the reason.

The study involved 71 middle-aged people recruited from the Wisconsin Registry for Alzheimer's Prevention (WRAP), of whom 29 met the criteria for metabolic syndrome (multiple cardiovascular and diabetes risk factors including abdominal obesity, high blood pressure, high blood sugar and high cholesterol).

Those with metabolic syndrome averaged 15% less blood flow to the brain than those without the syndrome.

One tried and true method of increasing blood flow to the brain is of course through exercise.

The study was presented at the Alzheimer's Association International Conference in Vancouver, Canada by Barbara Bendlin.

Damage to the retina (retinopathy) doesn’t produce noticeable symptoms in the early stages, but a new study indicates it may be a symptom of more widespread damage. In the ten-year study, involving 511 older women (average age 69), 7.6% (39) were found to have retinopathy. These women tended to have lower cognitive performance, and brain scans revealed that they had more areas of small vascular damage within the brain — 47% more overall, and 68% more in the parietal lobe specifically. They also had more white matter damage. They did not have any more brain atrophy.

These correlations remained after high blood pressure and diabetes (the two major risk factors for retinopathy) were taken into account. It’s estimated that 40-45% of those with diabetes have retinopathy.

Those with retinopathy performed similarly to those without on a visual acuity test. However, testing for retinopathy is a simple test that should routinely be carried out by an optometrist in older adults, or those with diabetes or hypertension.

The findings suggest that eye screening could identify developing vascular damage in the brain, enabling lifestyle or drug interventions to begin earlier, when they could do most good. The findings also add to the reasons why you shouldn’t ignore pre-hypertensive and pre-diabetic conditions.

Older adults who sleep poorly react to stress with increased inflammation

A study involving 83 older adults (average age 61) has found that poor sleepers reacted to a stressful situation with a significantly greater inflammatory response than good sleepers. High levels of inflammation increase the risk of several disorders, including cardiovascular disease and diabetes, and have been implicated in Alzheimer’s.

Each participant completed a self-report of sleep quality, perceived stress, loneliness and medication use. Around 27% were categorized as poor sleepers. Participants were given a series of tests of verbal and working memory designed to increase stress, with blood being taken before and after testing, as well as three more times over the next hour. The blood was tested for levels of a protein marker for inflammation (interleukin-6).

Poor sleepers reported more depressive symptoms, more loneliness and more perceived stress compared to good sleepers. Before cognitive testing, levels of IL-6 were the same for poor and good sleepers. However, while both groups showed increases in IL-6 after testing, poor sleepers showed a significantly larger increase — as much as four times larger and at a level found to increase risk for illness and death in older adults.

After accounting for loneliness, depression or perceived stress, this association remained. Surprisingly, there was no evidence that poor sleep led to worse cognitive performance, thus causing more stress. Poor sleepers did just as well on the tests as the good sleepers (although I note that we cannot rule out that poor sleepers were having to put in more effort to achieve the same results). Although there was a tendency for poor sleepers to be in a worse mood after testing (perhaps because they had to put in more effort? My own speculation), this mood change didn’t predict the increased inflammatory response.

The findings add to evidence that poor sleep (unfortunately common as people age) is an independent risk factor for cognitive and physical health, and suggest we should put more effort into dealing with it, rather than just accepting it as a corollary of age.

REM sleep disorder doubles risk of MCI, Parkinson's

A recent Mayo Clinic study has also found that people with rapid eye movement sleep behavior disorder (RBD) have twice the risk of developing mild cognitive impairment or Parkinson’s disease. Some 34% of those diagnosed with probable RBD developed MCI or Parkinson's disease within four years of entering the study, a rate 2.2 times greater than those with normal REM sleep.

Earlier research has found that 45% of those with RBD developed MCI or Parkinson's disease within five years of diagnosis, but these findings were based on clinical patients. The present study involved cognitively healthy older adults (70-89) participating in a population-based study of aging, who were diagnosed for probable RBD on the basis of the Mayo Sleep Questionnaire.

A study involving 130 HIV-positive people has found that memory impairment was associated with a significantly larger waistline.

Some 40% of participants (average age 46) had impaired cognition. This group had an average waist circumference of 39 inches, compared to 35 inches for those without such problems. Memory impairment was also linked to diabetes in those older than 55 (15% of those with memory problems had diabetes compared to only 3% of those without memory problems).

Waistline was more important than BMI. Unfortunately, some anti-HIV drugs cause weight gain in this area.

The finding is consistent with evidence that abdominal weight is more important than overall weight for cognitive impairment and dementia in the general population.

For more about HIV-related cognitive impairment

Why is diabetes associated with cognitive impairment and even dementia in older adults? New research pinpoints two molecules that trigger a cascade of events that end in poor blood flow and brain atrophy.

The study involved 147 older adults (average age 65), of whom 71 had type 2 diabetes and had been taking medication to manage it for at least five years. Brain scans showed that the diabetic patients had greater blood vessel constriction than the age- and sex-matched controls, and more brain atrophy. The reduction in brain tissue was most marked in the grey matter in the parietal and occipital lobes and cerebellum. Research has found that, at this age, while the average brain shrinks by about 1% annually, a diabetic brain might shrink by as much as 15%. Diabetics also had more white matter hyperintensities in the temporal, parietal and occipital lobes.

Behaviorally, the diabetics also had greater depression, slower walking, and executive dysfunction.

The reduced performance of blood vessels (greater vasoconstriction, blunted vasodilatation), and increased brain atrophy in the frontal, temporal, and parietal lobes, was associated with two adhesion molecules – sVCAM and sICAM. White matter hyperintensities were not associated with the adhesion molecules, inflammatory markers, or blood vessel changes.

It seems that the release of these molecules, probably brought about by chronic hyperglycemia and insulin resistance, produces chronic inflammation, which in turn brings about constricted blood vessels, reduced blood flow, and finally loss of neurons. The blood vessel constriction and the brain atrophy were also linked to higher glucose levels.

The findings suggest that these adhesion molecules provide two biomarkers of vascular health that could enable clinicians to recognize impending brain damage, that could then perhaps be prevented.

The findings also add weight to the growing evidence that diabetes management is crucial in preventing cognitive decline.

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, R. A., Ghosh-Dastidar B., Margolis K. L., Slaughter M. E., Jewell A., Bird C. E., et al.
(2011).  Neighborhood Socioeconomic Status and Cognitive Function in Women.
Am J Public Health. 101(9), 1721 - 1728.

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.

Growing evidence links obesity and poorer cognitive performance. Many factors associated with obesity, such as high blood pressure, type 2 diabetes and sleep apnea, damage the brain.

A study involving109 bariatric surgery patients and 41 obese control subjects has found that the bariatric surgery patients demonstrated improved memory and concentration 12 weeks after surgery, improving from the slightly impaired range to the normal range. That of the obese controls actually declined over this period. The improvement of those who had surgery seemed to be particularly related to improved blood pressure.

Study participants will be tested one year and two years after surgery.

[2224] Gunstad, J., Strain G., Devlin M. J., Wing R., Cohen R. A., Paul R. H., et al.
(2010).  Improved memory function 12 weeks after bariatric surgery.
Surgery for Obesity and Related Diseases.

The new label of ‘metabolic syndrome’ applies to those having three or more of the following risk factors: high blood pressure, excess belly fat, higher than normal triglycerides, high blood sugar and low high-density lipoprotein (HDL) cholesterol (the "good" cholesterol). Metabolic syndrome has been linked to increased risk of heart attack.

A new French study, involving over 7,000 older adults (65+) has found that those with metabolic syndrome were 20% more likely to show cognitive decline on a memory test (MMSE) over a two or four year interval. They were also 13% more likely to show cognitive decline on a visual working memory test. Specifically, higher triglycerides and low HDL cholesterol were linked to poorer memory scores; diabetes (but not higher fasting blood sugar) was linked to poorer visual working memory and word fluency scores.

The findings point to the importance of managing the symptoms of metabolic syndrome.

High cholesterol and blood pressure in middle age tied to early memory problems

Another study, involving some 4800 middle-aged adults (average age 55), has found that those with higher cardiovascular risk were more likely to have lower cognitive function and a faster rate of cognitive decline over a 10-year period. A 10% higher cardiovascular risk was associated not only with increased rate of overall mental decline, but also poorer cognitive test scores in all areas except reasoning for men and fluency for women.

The cardiovascular risk score is based on age, sex, HDL cholesterol, total cholesterol, systolic blood pressure and whether participants smoked or had diabetes.

Memory problems may be sign of stroke risk

A very large study (part of the REGARDS study) tested people age 45 and older (average age 67) who had never had a stroke. Some 14,842 people took a verbal fluency test, and 17,851 people took a word recall memory test. In the next 4.5 years, 123 participants who had taken the verbal fluency test and 129 participants who had taken the memory test experienced a stroke.

Those who had scored in the bottom 20% for verbal fluency were 3.6 times more likely to develop a stroke than those who scored in the top 20%. For the memory test, those who scored in the bottom 20% were 3.5 times more likely to have a stroke than those in the top quintile.

The effect was greatest at the younger ages. At age 50, those who scored in the bottom quintile of the memory test were 9.4 times more likely to later have a stroke than those in the top quintile.

 

Together, these studies, which are consistent with many previous studies, confirm that cardiovascular problems and diabetes add to the risk of greater cognitive decline (and possible dementia) in old age. And point to the importance of treating these problems as soon as they appear.

[2147] Raffaitin, C., Féart C., Le Goff M., Amieva H., Helmer C., Akbaraly T. N., et al.
(2011).  Metabolic syndrome and cognitive decline in French elders.
Neurology. 76(6), 518 - 525.

The findings of the second and third studies are to be presented at the American Academy of Neurology's 63rd Annual Meeting in Honolulu April 9 to April 16, 2011

Lesions of the brain microvessels include white-matter hyperintensities and the much less common silent infarcts leading to loss of white-matter tissue. White-matter hyperintensities are common in the elderly, and are generally regarded as ‘normal’ (although a recent study suggested we should be less blasé about them — that ‘normal’ age-related cognitive decline reflects the presence of these small lesions). However, the degree of white-matter lesions is related to the severity of decline (including increasing the risk of Alzheimer’s), and those with hypertension or diabetes are more likely to have a high number of them.

A new study has investigated the theory that migraines might also lead to a higher number of white-matter hyperintensities. The ten-year French population study involved 780 older adults (65+; mean age 69). A fifth of the participants (21%) reported a history of severe headaches, of which 71% had migraines.

Those with severe headaches were twice as likely to have a high quantity of white-matter hyperintensities as those without headaches. However, there was no difference in cognitive performance between the groups. Those who suffered from migraines with aura (2% of the total), also showed an increased number of silent cerebral infarcts — a finding consistent with other research showing that people suffering from migraine with aura have an increased risk of cerebral infarction (or strokes). But again, no cognitive decline was observed.

The researchers make much of their failure to find cognitive impairment, but I would note that, nevertheless, the increased number of brain lesions does suggest that, further down the track, there is likely to be an effect on cognitive performance. Still, headache sufferers can take comfort in the findings, which indicate the effect is not so great that it shows up in this decade-long study.

Previous research has indicated that obesity in middle-age is linked to higher risk of cognitive decline and dementia in old age. Now a study of 32 middle-aged adults (40-60) has revealed that although obese, overweight and normal-weight participants all performed equally well on a difficult cognitive task (a working memory task called the 2-Back task), obese individuals displayed significantly lower activation in the right inferior parietal cortex. They also had lower insulin sensitivity than their normal weight and overweight peers (poor insulin sensitivity may ultimately lead to diabetes). Analysis pointed to the impaired insulin sensitivity mediating the relationship between task-related activation in that region and BMI.

This suggests that it is insulin sensitivity that is responsible for the higher risk of cognitive impairment later in life. The good news is that insulin sensitivity is able to be modified through exercise and diet.

A follow-up study to determine if a 12-week exercise intervention can reverse the differences is planned.

Type 2 diabetes is known to increase the risk of cognitive impairment in old age. Now analysis of data from 41 older diabetics (aged 55-81) and 458 matched controls in the Victoria Longitudinal Study has revealed that several other factors make it more likely that an older diabetic will develop cognitive impairment. These factors are: having higher (though still normal) blood pressure, having gait and balance problems, and/or reporting yourself to be in bad health regardless of actual problems.

Diabetes and hypertension often go together, and both are separately associated with greater cognitive impairment and dementia risk, so it is not surprising that higher blood pressure is one of the significant factors that increases risk. The other factors are less expected, although gait and balance problems have been linked to cognitive impairment in a recent study, and they may be connected to diabetes through diabetes’ effect on nerves. Negativity about one’s health may reflect emotional factors such as anxiety, stress, or depression, although depression and well-being measures were not themselves found to be mediating effects for cognitive impairment in diabetics (Do note that this study is not investigating which factors, in general, are associated with age-related cognitive impairment; it is trying to establish which factors are specifically sensitive to cognitive impairment in older diabetics).

In the U.S., type 2 diabetes occurs in over 23% of those over 60; in Canada (where this study took place) the rate is 19%. It should be noted that the participants in this study are not representative of the general population, in that they were fairly well-educated older Canadians, most of whom have benefited from a national health care system. Moreover, the study did not have longitudinal data on these various factors, meaning that we don’t know the order of events (which health problems come first? How long between the development of the different problems?). Nevertheless, the findings provide useful markers to alert diabetics and health providers.

A small study comparing 18 obese adolescents with type 2 diabetes and equally obese adolescents without diabetes or pre-diabetes has found that those with diabetes had significantly impaired cognitive performance, as well as clear abnormalities in the integrity of their white matter (specifically, reduced white matter volume, especially in the frontal lobe, as well as impaired integrity in both white and grey matter). Similar abnormalities have previously been found in adults with type 2 diabetes, but the subjects were elderly and, after many years of diabetes, generally had significant vascular disease. One study involving middle-aged diabetics found a reduction in the volume of the hippocampus, which was directly associated with poor glycaemic control.

It remains to be seen whether such changes can be reversed by exercise and diet interventions. While those with diabetes performed worse in all cognitive tasks tested, the differences were only significant for intellectual functioning, verbal memory and psychomotor efficiency.

A study involving over 1000 older men and women (60-75) with type-2 diabetes has found that those with higher levels of the stress hormone cortisol in their blood are more likely to have experienced cognitive decline. Higher fasting cortisol levels were associated with greater estimated cognitive decline in general intelligence, working memory and processing speed. This was independent of mood, education, metabolic variables and cardiovascular disease. Strategies aimed at lowering stress levels may be helpful for older diabetics.

Studies on the roundworm C. elegans have revealed that the molecules required for learning and memory are the same from C. elegans to mammals, suggesting that the basic mechanisms underlying learning and memory are ancient, and that this animal can serve as a testing ground for treatments for age-related memory loss. Intriguingly, a comparison of two known regulators of longevity — reducing calorie intake and reducing activity in the insulin-signaling pathway (achieved through genetic manipulation) — has found that these two treatments produce very different effects on memory. While dietary restriction impaired memory in early adulthood, it maintained memory with age. On the other hand, reduced insulin signaling improved early adult memory performance but failed to preserve it with age. These different effects appear to be linked to expression of CREB, a protein known to be important for long-term memory. Young roundworms with defective insulin receptors had higher levels of CREB protein, while those worms genetically altered to eat less had low levels, but the level did not diminish with age. These findings add to our understanding of why memory declines with age.

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

Diabetic episodes affect memory

A study involving 62 children with type 1 diabetes, of whom 33 had experienced diabetic ketoacidosis, has found those with such experience performed significantly worse on a memory test that tested their ability to recall events in association with specific details. The finding points to the importance of avoiding diabetic ketoacidosis, which is avoidable in those known to have diabetes.

[1384] Ghetti, S., Lee J. K., Sims C. E., DeMaster D. M., & Glaser N. S.
(2010).  Diabetic Ketoacidosis and Memory Dysfunction in Children with Type 1 Diabetes.
The Journal of Pediatrics. 156(1), 109 - 114.

http://www.eurekalert.org/pub_releases/2009-10/uoc--dea101909.php

Poor glucose control linked to cognitive impairment in diabetics

The ongoing Memory in Diabetes (MIND) study, involving some 3,000 type 2 diabetics 55 years and older, has found that cognitive functioning abilities drop as average blood sugar levels rise. However, there was no connection between daily blood glucose levels and cognitive performance. The study adds to growing evidence that poorer blood glucose control is strongly associated with poorer memory function, that may eventually lead to mild cognitive impairment, vascular dementia and Alzheimer's disease. It is also possible that people with impaired cognitive ability are less compliant in taking medications and controlling their diabetes. Further research will test the hypothesis that improving glucose control results in improved cognitive function.

[797] Marcovina, S. M., Launer L. J., Cukierman-Yaffe T., Gerstein H. C., Williamson J. D., Lazar R. M., et al.
(2009).  Relationship Between Baseline Glycemic Control and Cognitive Function in Individuals With Type 2 Diabetes and Other Cardiovascular Risk Factors.
Diabetes Care. 32(2), 221 - 226.

http://www.eurekalert.org/pub_releases/2009-02/wfub-hbs021109.php

Adult-onset diabetes slows mental functioning in several ways, with deficits appearing early

A comparison of 41 adults with diabetes and 424 adults in good health, aged between 53 and 90, has revealed that healthy adults performed significantly better than adults with diabetes on two of the five domains tested: executive functioning and speed of processing. There were no significant differences on tests of episodic and semantic memory, verbal fluency, reaction time and perceptual speed. The effect remained even when only the younger group (those below 70) were analyzed, indicating that the diabetes-linked cognitive deficits appear early and remain stable.

[796] Yeung, S. E., Fischer A. L., & Dixon R. A.
(2009).  Exploring effects of type 2 diabetes on cognitive functioning in older adults.
Neuropsychology. 23(1), 1 - 9.

http://www.eurekalert.org/pub_releases/2009-01/apa-ads123008.php

Blood sugar linked to normal cognitive aging

Following research showing that decreasing brain function in the area of the hippocampus called the dentate gyrus is a main contributor of normal age-related cognitive decline, an imaging study has been investigating the cause of this decreasing function by looking at measures that typically change during aging, like rising blood sugar, body mass index, cholesterol and insulin levels. The study of 240 community-based nondemented elders (average age 80 years), of whom 60 had type 2 diabetes, found that decreasing activity in the dentate gyrus only correlated with levels of blood glucose. The same association was also found in aging rhesus monkeys and in mice. The finding suggests that maintaining blood sugar levels, even in the absence of diabetes, could help maintain aspects of cognitive health. It also suggests that one reason why physical exercise benefits memory may be its effect on lowering glucose levels.

[830] Mayeux, R., Vannucci S. J., Small S. A., Wu W., Brickman A. M., Luchsinger J., et al.
(2008).  The brain in the age of old: The hippocampal formation is targeted differentially by diseases of late life.
Annals of Neurology. 64(6), 698 - 706.

http://www.eurekalert.org/pub_releases/2008-12/cumc-rac121508.php

Diabetic seniors may experience memory declines after eating high-fat food

Growing evidence links diabetes to cognitive impairment. Now a small study of 16 adults (aged 50 years and older) with type 2 diabetes compared their cognitive performance on three separate occasions, fifteen minutes after consuming different meals. One meal consisted of high fat products – a danish pastry, cheddar cheese and yogurt with added whipped cream; the second meal was only water; and the third was the high-fat meal plus high doses of vitamins C (1000 mg) and E (800 IU) tablets. Researchers found that vitamin supplementation consistently improved recall scores relative to the meal alone, while those who ate the high fat meal without vitamin supplements showed significantly more forgetfulness of words and paragraph information in immediate and time delay recall tests. Those on water meal and meal with vitamins showed similar levels in cognitive performance. The finding indicates not only that diabetics can temporarily further worsen already underlying memory problems associated with the disease by consuming unhealthy meals, but also that this can be remedied by taking high doses of antioxidant vitamins C and E with the meal, suggesting that the effect of high-fat foods is to cause oxidative stress. However, this is hardly a recommended course of action, and the real importance of this finding is that it emphasizes the need for diabetics to consume healthy foods high in antioxidants, like fruits and vegetables. Of course, this is a very small study, and further replication is needed.

[1094] Chui, M., & Greenwood C.
(2008).  Antioxidant vitamins reduce acute meal-induced memory deficits in adults with type 2 diabetes.
Nutrition Research. 28(7), 423 - 429.

http://www.eurekalert.org/pub_releases/2008-06/bcfg-swt062408.php

Stress hormone impacts memory, learning in diabetic rodents

A rodent study sheds light on why diabetes can impair cognitive function. The study found that increased levels of a stress hormone (called cortisol in humans) in diabetic rats impaired synaptic plasticity and reduced neurogenesis in the hippocampus. When levels returned to normal, the hippocampus recovered. Cortisol production is controlled by the hypothalamic-pituitary axis (HPA). People with poorly controlled diabetes often have an overactive HPA axis and excessive cortisol.

[1050] Stranahan, A. M., Arumugam T. V., Cutler R. G., Lee K., Egan J. M., & Mattson M. P.
(2008).  Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons.
Nature Neuroscience. 11(3), 309 - 317.

http://www.eurekalert.org/pub_releases/2008-02/nioa-shi021508.php

Tight diabetes control does not impact cognitive ability in type 1 diabetes

A long-running study involving 1,441 type 1 diabetics, aged 13 to 39, has demonstrated that multiple episodes of severe hypoglycaemia, though they can cause confusion, irrational behavior, convulsions and unconsciousness, do not lead to long-term loss of cognitive ability.

[1120] The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications(DCCT/EDIC) Study Research
(2007).  Long-Term Effect of Diabetes and Its Treatment on Cognitive Function.
N Engl J Med. 356(18), 1842 - 1852.

http://www.eurekalert.org/pub_releases/2007-05/jdc-sst050107.php

Brain function not impaired by tight diabetes control and hypoglycemia

Previous research had indicated that tight blood glucose control -- achieved by taking three or more insulin injections daily – meant type 1 diabetics were three times as likely to suffer episodes of severe hypoglycemia, raising the fear that it might lead to a long-term loss of cognitive ability. Now a follow-up study provides the reassuring news that there was no link between multiple severe hypoglycemic reactions and impaired cognitive function in people with type 1 diabetes.

Jacobson, A.M. et al. 2006. Effects of Intensive and Conventional Treatment on Cognitive Function Twelve Years after the Completion of the Diabetes Control and Complications Trial (DCCT). Abstract Number 750232, presented at the American Diabetes Association's 66th Annual Scientific Sessions held in Washington, D.C, June 9—13.

http://www.eurekalert.org/pub_releases/2006-06/jdc-lss060806.php

Fat hormone linked to learning and memory

A new study reveals why obese patients who have diabetes also may have problems with their long-term memory. Leptin — the so-called ‘fat’ hormone — doesn't cross into the brain to help regulate appetite in obese people. Leptin also acts in the hippocampus, suggesting that leptin plays a role in learning and memory. The new study supports this by demonstrating that mice navigated a maze better after they received leptin. Moreover, mice with elevated levels of amyloid-beta plaques (characteristic of Alzheimer's) were particularly sensitive to leptin.

[2400] Farr, S. A., Banks W. A., & Morley J. E.
(2006).  Effects of leptin on memory processing.
Peptides. 27(6), 1420 - 1425.

http://www.sciencedaily.com/releases/2006/06/060614090511.htm
http://www.eurekalert.org/pub_releases/2006-06/slu-alb061306.php

Age-related vision problems may be associated with cognitive impairment

Age-related macular degeneration (AMD) develops when the macula, the portion of the eye that allows people to see in detail, deteriorates. An investigation into the relationship between vision problems and cognitive impairment in 2,946 patients has been carried out by The Age-Related Eye Disease Study (AREDS) Research Group. Tests were carried out every year for four years. Those who had more severe AMD had poorer average scores on cognitive tests, an association that remained even after researchers considered other factors, including age, sex, race, education, smoking, diabetes, use of cholesterol-lowering medications and high blood pressure. Average scores also decreased as vision decreased. It’s possible that there is a biological reason for the association; it is also possible that visual impairment reduces a person’s capacity to develop and maintain relationships and to participate in stimulating activities.

Chaves, P.H.M. et al. 2006. Association Between Mild Age-Related Eye Disease Study Research Group. 2006. Cognitive Impairment in the Age-Related Eye Disease Study: AREDS Report No. 16. Archives of Ophthalmology,124, 537-543.

http://www.eurekalert.org/pub_releases/2006-04/jaaj-avp040606.php

Review supports link between lifestyle factors and cognitive function in older adults

A review of 96 papers involving 36 very large, ongoing epidemiological studies in North America and Europe looking at factors involved in maintaining cognitive and emotional health in adults as they age has concluded that controlling cardiovascular risk factors, such as reducing blood pressure, reducing weight, reducing cholesterol, treating (or preferably avoiding) diabetes, and not smoking, is important for maintaining brain health as we age. The link between hypertension and cognitive decline was the most robust across studies. They also found a consistent close correlation between physical activity and brain health. However, they caution that more research is needed before specific recommendations can be made about which types of exercise and how much exercise are beneficial. They also found protective factors most consistently reported for cognitive health included higher education level, higher socio-economic status, emotional support, better initial performance on cognitive tests, better lung capacity, more physical exercise, moderate alcohol use, and use of vitamin supplements. Psychosocial factors, such as social disengagement and depressed mood, are associated with both poorer cognitive and emotional health in late life. Increased mental activity throughout life, such as learning new things, may also benefit brain health.

Wagster M, Hendrie H, Albert M, Butters M, Gao S, Knopman DS, Launer L, Yaffe K, Cuthbert B, Edwards E. The NIH Cognitive and Emotional Health ProjectReport of the Critical Evaluation Study Committee. Alzheimer's and Dementia [Internet]. 2006 ;2(1):12 - 32. Available from: http://www.alzheimersanddementia.com/article/S1552-5260(05)00503-0/abstract?articleId=&articleTitle=&citedBy=false&medlinePmidWithoutMDLNPrefix=&overridingDateRestriction=&related=false&restrictdesc_author=&restrictDescription=&restrictName.jalz=jalz&rest

http://www.eurekalert.org/pub_releases/2006-02/aa-nss021606.php

Risk for lowered cognitive performance greater in people at high risk for stroke

A new large-scale study supports earlier suggestions that those with a high risk for stroke within 10 years are also at risk for lowered cognitive function and show a pattern of deficits similar to that seen in mild vascular cognitive impairment. It is speculated that the reason may lie in structural and functional changes in the brain that do not rise to the level of clinical detection, and this is supported by a recent brain imaging study showing that abnormal brain atrophy is related both to higher risk of stroke and poorer cognitive ability. The probability of experiencing stroke within 10 years was calculated using weighted combinations of age, systolic blood-pressure, presence of diabetes, cigarette smoking, history of cardiovascular disease, treatment for hypertension and atrial fibrillation.

[1422] Elias, M. F., Sullivan L. M., D'Agostino R. B., Elias P. K., Beiser A., Au R., et al.
(2004).  Framingham stroke risk profile and lowered cognitive performance.
Stroke; a Journal of Cerebral Circulation. 35(2), 404 - 409.

http://www.eurekalert.org/pub_releases/2004-01/ama-rfl010804.php

Age-related changes in the brain's white matter affect cognitive function

From around age 60, "white-matter lesions" appear in the brain, significantly affecting cognitive function. But without cognitive data from childhood, it is hard to know how much of the difference in cognitive abilities between elderly individuals is due to aging. A longitudinal study has been made possible by the Scottish Mental Survey of 1932, which gave 11-year-olds a validated cognitive test. Scottish researchers have tracked down healthy living men and women who took part in this Survey and retested 83 participants. Testing took place in 1999, when most participants were 78 years old.
It was found that the amount of white-matter lesions made a significant contribution to general cognitive ability differences in old age, independent of prior ability. The amount of white-matter lesions contributed 14.4% of the variance in cognitive scores; early IQ scores contributed 13.7%. The two factors were independent.
Although white-matter lesions are viewed as a normal part of aging, they are linked with other health problems, in particular to circulatory problems (including hypertension, diabetes, heart disease and cardiovascular risk factors).

[442] Deary, I. J., Leaper S. A., Murray A. D., Staff R. T., & Whalley L. J.
(2003).  Cerebral white matter abnormalities and lifetime cognitive change: a 67-year follow-up of the Scottish Mental Survey of 1932.
Psychology and Aging. 18(1), 140 - 148.

http://www.eurekalert.org/pub_releases/2003-03/apa-aci031703.php

High sugar blood levels linked to poor memory

A new study takes an important step in explaining cognitive impairment in diabetics, and suggests a possible cause for some age-related memory impairment. The study assessed non-diabetic middle-aged and elderly people. Those with impaired glucose tolerance (a pre-diabetic condition) had a smaller hippocampus and scored worse on tests for recent memory. These results were independent of age or overall cognitive performance. The brain uses glucose almost exclusively as a fuel source. The ability to get glucose from the blood is reduced in diabetes. The study raises the possibility that exercise and weight loss, which help control blood sugar levels, may be able to reverse some of the memory loss that accompanies aging.

[543] Convit, A., Wolf O. T., Tarshish C., & de Leon M. J.
(2003).  Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly.
Proceedings of the National Academy of Sciences of the United States of America. 100(4), 2019 - 2022.

http://www.eurekalert.org/pub_releases/2003-02/nyum-hsb013003.php

Diabetes and high blood pressure linked to decline in mental ability

A large-scale six-year study of people aged 40 to 70 years old found that people with diabetes and high blood pressure are more likely to experience cognitive decline. Diabetes was associated with greater cognitive decline for those younger than 58 as well as those older than 58, but high blood pressure was a risk factor only for the 58 and older group.

[2534] Knopman, D. S., Boland L. L., Mosley T., Howard G., Liao D., Szklo M., et al.
(2001).  Cardiovascular risk factors and cognitive decline in middle-aged adults.
Neurology. 56(1), 42 - 48.

http://www.eurekalert.org/pub_releases/2001-01/MC-Nsld-0701101.php
http://www.eurekalert.org/pub_releases/2001-01/AAoN-Dahb-0801101.php

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