Persons with type 2 diabetes have a high risk of late-life cognitive impairment, and physical activity might be a potential target for modifying this risk. Therefore, the authors evaluated the association between physical activity level and cognition in women with type 2 diabetes. Beginning in 1995–2000, cognitive function was assessed in 1,550 Nurses’ Health Study participants aged ≥70 years with type 2 diabetes. Follow-up assessments were completed twice thereafter, at 2-year intervals. Multivariate-adjusted linear regression models were used to obtain mean differences in baseline cognitive scores and cognitive decline across tertiles of long-term physical activity. Initial results from age- and education-adjusted models indicated that greater physical activity levels were associated with better baseline cognition (for a global score averaging scores from 6 cognitive tests, P-trend = 0.02). However, results were substantially attenuated after adjustment for multiple potential confounders, largely because of physical disability indicators (global score: P-trend = 0.06); for example, the mean difference for the global score was 0.07 standard units (95% confidence interval: −0.01, 0.15) when comparing extreme tertiles. Results were similar for cognitive decline. These findings indicate little overall association between physical activity and cognition after adjustment for disability factors in older women with type 2 diabetes.
cognition; cohort studies; diabetes mellitus, type 2; exercise; women
Berries are high in flavonoids, especially anthocyanidins, and improve cognition in experimental studies. We prospectively evaluated whether greater long-term intakes of berries and flavonoids are associated with slower rates of cognitive decline in older women.
Beginning in 1980, a semi-quantitative food frequency questionnaire was administered every four years to Nurses’ Health Study participants. In 1995–2001, we began measuring cognitive function in 16,010 participants, aged ≥70 years; follow-up assessments were conducted twice, at two-year intervals. To ascertain long-term diet, we averaged dietary variables from 1980 through the initial cognitive interview. Using multivariable-adjusted, mixed linear regression, we estimated mean differences in slopes of cognitive decline by long-term berry and flavonoid intakes.
Greater intakes of blueberries and strawberries were associated with slower rates of cognitive decline (e.g., for a global score averaging all six cognitive tests, for blueberries: p-trend=0.014 and mean difference=0.04 [95% CI=0.01, 0.07] comparing extreme categories of intake; for strawberries: p-trend= 0.022 and mean difference=0.03 [95% CI=0.00, 0.06] comparing extreme categories of intake), after adjusting for multiple potential confounders. These effect estimates were equivalent to those we find for approximately 1.5 to 2.5 years of age in our cohort, indicating that berry intake appears to delay cognitive aging by up to 2.5 years. Additionally, in further supporting evidence, greater intakes of anthocyanidins and total flavonoids were associated with slower rates of cognitive decline (p-trends= 0.015 and 0.053, respectively, for the global score).
Higher intake of flavonoids, particularly from berries, appears to reduce rates of cognitive decline in older adults.
As a site of high metabolic activity, the brain is particularly susceptible to oxidative damage. We explored the association between plasma antioxidants and cognition. In 858 female participants of the Nurses’ Health Study, aged 70+ years, we measured plasma carotenoids and tocopherols in 1989–1990, and assessed cognitive function by telephone beginning in 1995–2001; assessments were repeated twice at two-year intervals. We used linear regression to estimate multivariable-adjusted mean cognitive performance at the initial assessment by quartile of antioxidants, and longitudinal models for analyzing cognitive decline over four years. Higher antioxidant levels were not associated with initial performance or decline. Mean difference in initial global composite score (averaging all 6 cognitive tests) for the top versus bottom quartile of total carotenoids was −0.05 standard units (95% confidence interval [CI] −0.19, 0.09), and 0.04 units for total tocopherols (95% CI −0.10, 0.18). Individual antioxidants were not associated with cognition. Overall, total plasma carotenoids or tocopherols were not related to cognition in women.
Individuals with type 2 diabetes have high risk of late-life cognitive impairment, yet little is known about strategies to modify risk. Targeting insulin resistance and vascular complications—both associated with cognitive decline—may be a productive approach. We investigated whether dietary fat, which modulates glucose and lipid metabolism, might influence cognitive decline in older adults with diabetes.
RESEARCH DESIGN AND METHODS
Beginning in 1995–1999, we evaluated cognitive function in 1,486 Nurses' Health Study participants, aged ≥70 years, with type 2 diabetes; second evaluations were conducted 2 years later. Dietary fat intake was assessed regularly beginning in 1980; we considered average intake from 1980 (at midlife) through initial cognitive interview and also after diabetes diagnosis. We used multivariate-adjusted linear regression models to obtain mean differences in cognitive decline across tertiles of fat intake.
Higher intakes of saturated and trans fat since midlife, and lower polyunsaturated to saturated fat ratio, were each highly associated with worse cognitive decline in these women. On a global score averaging all six cognitive tests, mean decline among women in the highest trans fat tertile was 0.15 standard units worse than that among women in the lowest tertile (95% CI −0.24 to −0.06, P = 0.002); this mean difference was comparable with the difference we find in women 7 years apart in age. Results were similar when we analyzed diet after diabetes diagnosis.
These findings suggest that lower intakes of saturated and trans fat and higher intake of polyunsaturated fat relative to saturated fat may reduce cognitive decline in individuals with type 2 diabetes.
To test the hypothesis that type 2 diabetes is associated with greater decline in cognitive function in middle-aged individuals.
RESEARCH DESIGN AND METHODS
In the Dutch prospective Doetinchem Cohort Study, cognitive functioning was measured twice within a 5-year time interval in 2,613 men and women. Participants were aged 43–70 years at baseline (1995–2002), and no one had a history of stroke. Change in scores on global cognitive function as well as on specific cognitive function domains (memory, speed of cognitive processes, and cognitive flexibility) were compared for respondents with and without type 2 diabetes (verified by the general practitioner or random plasma glucose levels ≥11.1 mmol/l).
At the 5-year follow-up, the decline in global cognitive function in diabetic patients was 2.6 times greater than that in individuals without diabetes. For individuals aged ≥60 years, patients with incident and prevalent diabetes showed a 2.5 and 3.6 times greater decline, respectively, in cognitive flexibility than individuals without diabetes. For most cognitive domains, the magnitude of cognitive decline in patients with incident diabetes was intermediate between that of individuals without diabetes and that of patients with diabetes at baseline.
Middle-aged individuals with type 2 diabetes showed a greater decline in cognitive function than middle-aged individuals without diabetes.
Objective To examine the association of type 2 diabetes with baseline cognitive function and cognitive decline over two years of follow up, focusing on women living in the community and on the effects of treatments for diabetes.
Design Nurses' health study in the United States. Two cognitive interviews were carried out by telephone during 1995-2003.
Participants 18 999 women aged 70-81 years who had been registered nurses completed the baseline interview; to date, 16 596 participants have completed follow up interviews after two years.
Main outcome measures Cognitive assessments included telephone interview of cognitive status, immediate and delayed recalls of the East Boston memory test, test of verbal fluency, delayed recall of 10 word list, and digit span backwards. Global scores were calculated by averaging the results of all tests with z scores.
Results After multivariate adjustment, women with type 2 diabetes performed worse on all cognitive tests than women without diabetes at baseline. For example, women with diabetes were at 25-35% increased odds of poor baseline score (defined as bottom 10% of the distribution) compared with women without diabetes on the telephone interview of cognitive status and the global composite score (odds ratios 1.34, 95% confidence interval 1.14 to 1.57, and 1.26, 1.06 to 1.51, respectively). Odds of poor cognition were particularly high for women who had had diabetes for a long time (1.52, 1.15 to 1.99, and 1.49, 1.11 to 2.00, respectively, for ≥ 15 years' duration). In contrast, women with diabetes who were on oral hypoglycaemic agents performed similarly to women without diabetes (1.06 and 0.99), while women not using any medication had the greatest odds of poor performance (1.71, 1.28 to 2.281, and 1.45, 1.04 to 2.02) compared with women without diabetes. There was also a modest increase in odds of poor cognition among women using insulin treatment. All findings were similar when cognitive decline was examined over time.
Conclusions Women with type 2 diabetes had increased odds of poor cognitive function and substantial cognitive decline. Use of oral hypoglycaemic therapy, however, may ameliorate risk.
Both type 2 diabetes and hyperinsulinemia have been related to diminished cognition. To address independent effects of increasing mid-life insulin secretion on late-life cognition, we prospectively examined the relation of plasma c-peptide levels to cognitive decline in a large sample of older women without diabetes or stroke.
Plasma c-peptide levels were measured in 1,187 “young-old” women (mean age=64 years) without diabetes in the Nurses’ Health Study. Cognitive decline was assessed approximately 10 years later. Three repeated cognitive batteries were administered over an average of 4.4 years using telephone-based tests of general cognition, verbal memory, category fluency, and attention. Primary outcomes were general cognition (measured by the Telephone interview for Cognitive Status [TICS], as well as a global score averaging all tests) and a verbal memory score averaging 4 tests of word-list and paragraph recall. Linear mixed effects models were used to compute associations between c-peptide levels and rates of cognitive decline.
Higher c-peptide levels were associated with faster decline in global cognition and verbal memory. Compared to those in the lowest c-peptide quartile, multivariable-adjusted mean differences (95% CI) in rates of decline for women in the highest quartile were −0.03 (−0.06, − 0.00) units/year for the global score, and −0.05 (−0.09, −0.02) units/year for verbal memory. Each one standard-deviation increase in c-peptide was associated with significantly faster decline on the TICS (p-trend=0.05), global score (p-trend=0.04) and verbal memory (p-trend=0.006).
Higher levels of insulin secretion in those without diabetes may be related to decline in general cognition and verbal memory.
insulin; c-peptide; diabetes; cognitive decline; aging
Cerebral microvascular disease associated with type 2 diabetes may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral microcirculations; a hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with type 2 diabetes.
RESEARCH DESIGN AND METHODS
In the population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60–75 years with type 2 diabetes underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using a modification of the Early Treatment of Diabetic Retinopathy Scale.
After age and sex adjustment, a significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency, mental flexibility, and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, sociodemographic characteristics, cardiovascular risk factors, and macrovascular disease.
DR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation.
To determine whether metabolic syndrome is associated with accelerated cognitive decline in community-dwelling older adults.
Longitudinal study of 993 adults (mean 66.8 ± 8.7 years) from the Rancho Bernardo Study. Metabolic syndrome components, defined by 2001 NCEP-ATP III criteria, were measured in 1984–87. Cognitive function was first assessed in 1988–92. Cognitive assessments were repeated approximately every four years, for a maximum 16-year follow-up. Mixed-effects models examined longitudinal rate of cognitive decline by metabolic syndrome status, controlling for factors plausibly associated with cognitive function (diabetes, inflammation).
Metabolic syndrome was more common in men than women (14% vs. 9%, p=0.01). In women, metabolic syndrome was associated with greater executive function and long term memory decline. These associations did not differ by inflammatory biomarker levels. Diabetes did not alter the association of metabolic syndrome with long-term recall but modified the association with executive function: metabolic syndrome was associated with accelerated executive function decline in diabetic women only. Metabolic syndrome was not related to rate of decline on any cognitive measure in men.
Metabolic syndrome was a risk factor for accelerated cognitive decline, but only in women. Prevention of metabolic syndrome may aid in maintenance of cognitive function with age.
Aging; cognition; inflammation; diabetes; memory; executive function
To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes.
RESEARCH DESIGN AND METHODS
A cross-sectional study of 1,066 men and women aged 60–75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary–based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing.
Higher IL-6 and TNF-α levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients −0.074 to −0.173 (P < 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, IL-6 remained associated with three of the cognitive tests and with g.
In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline.
longitudinal studies have reported that smoking increases risk for
cognitive impairment and that moderate alcohol intake could be
preventive.The association between both cigarette smoking and alcohol
drinking and incident cognitive impairment was studied in a
METHODS—This is a 1 year prospective population based cohort sudy of all residents aged 65 or over in the electoral ward of Gospel Oak in London, UK (n=889).
Cognitive impairment was assessed at baseline and 1 year later using
the organic brain syndrome (OBS) cognitive impairment scale from the
short CARE structured assessment. Subjects who were cognitively
impaired at baseline were excluded from this analysis.
of OBS cognitive impairment was 10.4% at index assessment and the 1 year cumulative incidence of cognitive impairment was 5.7%. Cognitive
impairment was not associated with use of alcohol, although there was a
non-significant association in the direction of a protective effect
against onset of cognitive impairment for moderate drinkers compared
with non-drinkers and heavy drinkers. Current smoking status predicted
cognitive impairment (risk ratio (RR) 3.7; (95% confidence interval
(95% CI)=1.1-12.3) independently from sex, age, alcohol, occupational
class, education, handicap, depression, and baseline cognitive function.
seems to be a prospective risk factor for incident cognitive
impairment; thus encouragement of older people to stop smoking could be
considered as part of a strategy to reduce the incidence of cognitive impairment.
Associations between postmenopausal hormone therapy (HT) and cognitive decline may depend on apolipoprotein E (APOE) status or timing of initiation.
We included 16,514 Nurses’ Health Study participants aged 70–81 years who were followed since 1976 and completed up to three telephone cognitive assessments (2 years apart), between 1995 and 2006. The tests assessed general cognition (Telephone Interview of Cognitive Status (TICS)), verbal memory, and category fluency. We used longitudinal analyses to estimate differences in cognitive decline across hormone groups. APOE genotype was available in 3697 participants.
Compared with never users, past or current HT users showed modest but statistically significant worse rates of decline in the TICS: the multivariable-adjusted difference in annual rate of decline in the TICS among current estrogen only users versus never users was −0.04 (95% CI = −0.07, −0.004); for current estrogen+progestin users, the mean difference was −0.05 (95% CI = −0.10, −0.002). These differences were equivalent to those observed in women who are 1–2 years apart in age. We observed no protective associations with early timing of hormone initiation. We found suggestive interactions with APOE e4 status (e.g., on TICS, p-interaction = 0.10), where the fastest rate of decline was observed among APOE e4 carriers who were current HT users.
Regardless of timing of initiation, HT may be associated with worse rates of decline in general cognition, especially among those with an APOE e4 allele.
We reviewed 143 papers that described the relationship between moderate drinking of alcohol and some aspect of cognition. Two types of papers were found: (1) those that provided ratios of risk between drinkers and nondrinkers (74 papers in total) and (2) those that, although they did not provide such ratios, allowed cognition in drinkers to be rated as “better,” “no different,” or “worse” than cognition in nondrinkers (69 papers in total). The history of research on moderate drinking and cognition can be divided into two eras: 1977–1997 and 1998–present. Phase I (1977–1997) was the era of neuropsychological evaluation involving mostly young to middle-aged (18–50 years old) subjects. Although initial studies indicated moderate drinking impaired cognition, many later studies failed to confirm this, instead finding no difference in cognition between drinkers and nondrinkers. Phase II (1998–present) was and is the era of mental status exam evaluation involving mostly older (≥55 years old) subjects. These studies overwhelmingly found that moderate drinking either reduced or had no effect on the risk of dementia or cognitive impairment. When all the ratios of risk from all the studies in phase II providing such ratios are entered into a comprehensive meta-analysis, the average ratio of risk for cognitive risk (dementia or cognitive impairment/decline) associated with moderate “social” (not alcoholic) drinking of alcohol is 0.77, with nondrinkers as the reference group. The benefit of moderate drinking applied to all forms of dementia (dementia unspecified, Alzheimer’s disease, and vascular dementia) and to cognitive impairment (low test scores), but no significant benefit against cognitive decline (rate of decline in test scores) was found. Both light and moderate drinking provided a similar benefit, but heavy drinking was associated with nonsignificantly higher cognitive risk for dementia and cognitive impairment. Although the meta-analysis also indicated that wine was better than beer or spirits, this was based on a relatively small number of studies because most studies did not distinguish among these different types of alcohol. Furthermore, a number of the studies that did make the distinction reported no difference among the effects of these different types of alcohol. Therefore, at present this question remains unanswered. Analysis also showed that the presence of the apolipoprotein E epsilon 4 allele eliminated the benefit of moderate drinking. However, this was based on a relatively small number of studies and several other studies have found a beneficial effect of the epsilon e4 allele. Further studies are necessary to settle this question. The benefit of moderate alcohol for cognition was seen in both men and women, although the amount and pattern of drinking is very different between the two sexes. Lastly, the finding of unaffected or significantly reduced cognitive risk in light to moderate drinkers was seen in 14/19 countries for which country-specific ratio data were available, with three of the five remaining countries showing nonsignificant reductions as well. Overall, light to moderate drinking does not appear to impair cognition in younger subjects and actually seems to reduce the risk of dementia and cognitive decline in older subjects.
Alzheimer’s disease; dementia; drinking
We sought to determine if type 2 diabetes mellitus (T2DM) was associated with accelerated decline in domain-specific measures of cognitive function and fine motor speed.
Women aged 65–80 years who were enrolled in a clinical trial of postmenopausal hormone therapy were grouped as having T2DM (n=179) or not (n=1984) and followed for an average of 5 years with annual standardized assessments of domain-specific cognitive function. Mean patterns of cognitive measures over time were contrasted between groups using general linear models and Wald tests, with varying levels of covariate adjustment. The influences of age at onset, use of oral medications, and use of insulin were also examined.
T2DM was associated with mean deficits of 0.2–0.4 standard deviations (SD) across follow-up in most cognitive domains. Consistent evidence that rates of decline were accelerated among women with T2DM was evident only for verbal knowledge and verbal memory (p<0.05). Decrements in fine motor speed, but no measure of cognitive function, were greater for women with earlier onset T2DM. Use of oral diabetes medications was associated with better relative cognitive function.
In these women, T2DM was associated with cognitive deficits in most domains. Relative deficits in verbal knowledge and verbal memory may continue to increase after deficits in other domains have stabilized. Relative deficits in fine motor speed may be greater among women with earlier onsets of T2DM. Use of insulin, which may reflect greater T2DM severity, was associated with relatively greater cognitive deficits.
People with type 2 diabetes are at increased risk of cognitive impairment but the mechanism is uncertain. Elevated glucocorticoid levels in rodents and humans are associated with cognitive impairment. We aimed to determine whether fasting cortisol levels are associated with cognitive ability and estimated lifetime cognitive change in an elderly population with type 2 diabetes.
RESEARCH DESIGN AND METHODS
This was a cross-sectional study of 1,066 men and women aged 60–75 years with type 2 diabetes, living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study). Cognitive abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility were tested, and a general cognitive ability factor, g, was derived. Prior intelligence was estimated from vocabulary testing, and adjustment for scores on this test was used to estimate lifetime cognitive change. Relationships between fasting morning plasma cortisol levels and cognitive ability and estimated cognitive change were tested. Models were adjusted for potential confounding and/or mediating variables including metabolic and cardiovascular variables.
In age-adjusted analyses, higher fasting cortisol levels were not associated with current g or with performance in individual cognitive domains. However, higher fasting cortisol levels were associated with greater estimated cognitive decline in g and in tests of working memory and processing speed, independent of mood, education, metabolic variables, and cardiovascular disease (P < 0.05).
High morning cortisol levels in elderly people with type 2 diabetes are associated with estimated age-related cognitive change. Strategies targeted at lowering cortisol action may be useful in ameliorating cognitive decline in individuals with type 2 diabetes.
Consumption of large amounts of alcohol is known to have negative effects, but consumption in smaller amounts may be protective. The effect of alcohol may be greater in the elderly than in younger adults, particularly with regard to cognition. However, the drinking pattern that will provide optimal protection against dementia and cognitive decline in the elderly has not been systematically investigated. The present paper is a critical review of research on the effect of alcohol on cognitive function and dementia in the elderly. Studies published from 1971 to 2011 related to alcohol and cognition in the elderly were reviewed using a PubMed search. Alcohol may have both a neurotoxic and neuroprotective effect. Longitudinal and brain imaging studies in the elderly show that excessive alcohol consumption may increase the risk of cognitive dysfunction and dementia, but low to moderate alcohol intake may protect against cognitive decline and dementia and provide cardiovascular benefits. Evidence suggesting that low to moderate alcohol consumption in the elderly protects against cognitive decline and dementia exists; however, because of varying methodology and a lack of standardized definitions, these findings should be interpreted with caution. It is important to conduct more, well-designed studies to identify the alcohol drinking pattern that will optimally protect the elderly against cognitive decline and dementia.
Alcohol; Cognition; Neuroprotection; Neurotoxicity; Elderly; Dementia
Type 2 diabetes has been associated with an increased risk of dementia. To assess possible independent effects of insulin, we investigated the relation of insulin levels to cognitive decline in nondiabetic women.
Fasting plasma insulin levels were measured in mid-life in 1,416 nondiabetic Nurses’ Health Study participants, who also completed cognitive testing that began 10 years later (current age: 70–75 years). Over 4 years, 3 assessments of general cognition, verbal memory, category fluency and attention were administered. Primary outcomes were the Telephone Interview for Cognitive Status (TICS) performance, the global score (average of all tests) and verbal memory (average of verbal recall tests). Linear mixed-effects models were used to calculate the association between insulin and cognitive decline.
Higher insulin levels were associated with a faster decline on the TICS and verbal memory. For analysis, batch-specific quartiles of insulin levels were constructed. Compared to the lowest quartile, adjusted differences in the annual rates of decline (with 95% CI values in parentheses) for the second, third and fourth quartiles were: TICS, −0.06 (−0.16, 0.03), −0.14 (−0.24, −0.04), and −0.09 (−0.19, 0.01) points (p trend = 0.04); verbal memory, −0.01 (−0.04, 0.02), −0.05 (−0.08, −0.02), and −0.02 (−0.05, 0.01) units (p trend = 0.02). These associations remained after multivariable adjustment.
Our study provides evidence for a potential role of higher fasting insulin levels in cognitive decline, possibly independent of diabetes.
Diabetes; Insulin, cognitive performance; Aging, cognitive decline; Dementia
Observational studies have generated conflicting evidence on the effects of moderate maternal alcohol consumption during pregnancy on offspring cognition mainly reflecting problems of confounding. Among mothers who drink during pregnancy fetal alcohol exposure is influenced not only by mother’s intake but also by genetic variants carried by both the mother and the fetus. Associations between children’s cognitive function and both maternal and child genotype at these loci can shed light on the effects of maternal alcohol consumption on offspring cognitive development.
We used a large population based study of women recruited during pregnancy to determine whether genetic variants in alcohol metabolising genes in this cohort of women and their children were related to the child’s cognitive score (measured by the Weschler Intelligence Scale) at age 8.
We found that four genetic variants in alcohol metabolising genes in 4167 children were strongly related to lower IQ at age 8, as was a risk allele score based on these 4 variants. This effect was only seen amongst the offspring of mothers who were moderate drinkers (1–6 units alcohol per week during pregnancy (per allele effect estimates were −1.80 (95% CI = −2.63 to −0.97) p = 0.00002, with no effect among children whose mothers abstained during pregnancy (0.16 (95%CI = −1.05 to 1.36) p = 0.80), p-value for interaction = 0.009). A further genetic variant associated with alcohol metabolism in mothers was associated with their child’s IQ, but again only among mothers who drank during pregnancy.
Cognitive reserve is associated with a lower risk of dementia but the extent to which it shapes cognitive aging trajectories remains unclear. Our objective is to examine the impact of three markers of reserve from different points in the lifecourse on cognitive function and decline in late adulthood.
Data are from 5234 men and 2220 women, mean age 56 years (standard deviation=6) at baseline, from the Whitehall II cohort study. Memory, reasoning, vocabulary, phonemic and semantic fluency were assessed three times over 10 years. Linear mixed models were used to assess the association between markers of reserve (height, education, and occupation) and cognitive decline, using the 5 cognitive tests and a global cognitive score composed of these tests.
All three reserve measures were associated with baseline cognitive function, with strongest associations with occupation and the weakest with height. All cognitive functions except vocabulary declined over the 10 year follow-up period. On the global cognitive test, there was greater decline in the high occupation group (−0.27; 95% confidence interval (CI): −0.28, −0.26) compared to the intermediate (−0.23; 95% CI: −0.25, −0.22) and low groups (−0.21; 95% CI: −0.24, −0.19); p=0.001. The decline in reserve groups defined by education (p=0.82) and height (p=0.55) was similar.
Cognitive performance over the adult lifecourse was remarkably higher in the high reserve groups. However, rate of cognitive decline did not differ between reserve groups except occupation where there was some evidence of greater decline in the high occupation group.
Prospectively assess effects of select dietary fats on cognitive decline
Prospective observational; 3-year follow-up
Subjects recruited at Northwestern University who participated in Women's Health Initiative Observational Study or control group of Diet Modification arm.
482 women ≥ 60 years
We averaged dietary intake from a validated food frequency questionnaire (FFQ) administered twice (mean=2.7 years apart) before baseline cognitive assessment (mean=2.9 years after 2nd FFQ). Testing of memory, vision, executive function, language, and attention was performed at 2 time points, 3 years apart. We created a global Z-score for both time points by averaging all Z-scores for each participant and defined global cognitive change as the difference between follow-up and baseline Z-scores.
Median intakes of saturated fats (SFA), trans-fats, (TFA), dietary cholesterol (DC) and monounsaturated fats (MUFA) were 18.53 g/d, 3.45 g/d, 0.201 g/d and 19.39 g/d, respectively. There were no associations between degree of cognitive decline and intakes of SFA (p=0.69), TFA (p=0.54) or DC (p=0.64) after adjusting for baseline cognition, total energy, age, education, reading ability, Apolipoprotein E (ε4) allele, BMI, estrogen and beta-blocker use, and intake of caffeine and other fatty acids. In contrast, compared with participants in the lowest quartile, MUFA intake was associated with lower cognitive decline in fully adjusted linear regression models, with decline of 0.21 + 0.05 SE in the lowest versus 0.05 + 0.05 SE in the highest quartiles (p=0.02). This effect of MUFA intake was primarily in the visual and memory domains (p=0.03 for both).
Higher intakes of SFA, TFA and DC in these women were not associated with cognitive decline, while MUFA intake was associated with less cognitive decline.
Fatty acids; cognitive decline; monounsaturated fat intake and prospective
To examine the relationship between reduced heart rate variability (HRV) and cognitive function in middle aged adults in the general population
HRV, in both time and frequency domains, and cognitive function were measured twice, at mean ages 55 and 61 years, in 5,375 male and female participants of the UK Whitehall II study. Logistic regression was used to model associations between HRV and cognition (short-term verbal memory, reasoning (AH4-I), vocabulary, phonemic and semantic fluency). Cross-sectional associations were assessed at both waves and longitudinal associations as change in cognition over the 5 year follow-up.
No consistent associations were found in men or women, either in cross-section, prospective or the longitudinal analysis of decline in cognition.
Reduced cardiovascular autonomic function does not contribute to cognitive impairment in this middle-aged population. Further studies are needed to verify the potential role of HRV measures in predicting the degeneration of cognitive function at older ages.
autonomic function; cognitive impairment; heart rate variability; cohort studies
To examine the relationship between reduced heart rate variability (HRV) and cognitive function in middle-aged adults in the general population.
HRV, in both time and frequency domains, and cognitive functioning were measured twice in 5,375 male and female participants of the UK Whitehall II study (mean ages = 55 and 61 years, respectively). Logistic regression was used to model associations between HRV and cognition [short-term verbal memory, reasoning (Alice Heim 4-I), vocabulary, phonemic and semantic fluency]. Cross-sectional associations were assessed at both waves, and longitudinal associations were measured as changes in cognition over the 5-year follow-up.
No consistent associations were found in men or women, either in the cross-sectional, prospective or the longitudinal analyses of declines in cognition.
Reduced cardiovascular autonomic function does not contribute to cognitive impairment in this middle-aged population. Further studies are needed to verify the potential role of HRV measures in predicting the degeneration of cognitive function at older ages.
Autonomic function; Cognitive impairment; Heart rate variability; Cohort studies
The literature remains contentious regarding the separate and combined effects of moderate drinking and ERT (Estrogen Replacement Therapy) on cognition. In the current study, the authors sought to disentangle the predictive utility of alcohol use, ERT and their interaction on the episodic and semantic memory stores of postmenopausal women. It was predicted that relationships between moderate drinking, ERT and cognition would be attenuated by demographic and health-related factors.
Postmenopausal women (N=298) completed a battery of cognitive tests designed to assess speed and accuracy of episodic and knowledge-based cognitive processing. Potentially confounding variables were categorized and tested as mediators in hierarchical regression analyses.
Moderate drinking was a weak predictor of episodic availability prior to removal of potential mediators. ERT use was a significant predictor of episodic and knowledge-based availability; no mediators were identified. Alcohol moderated ERT, as a combined alcohol/ERT variable was shown to be related to cognition. Neither moderate drinking nor ERT use was associated with cognitive speed.
These findings suggest that positive relationships between alcohol and cognition are likely mediated by other variables and should not be regarded as a benefit of drinking. Further, results support ERT as a predictor of knowledge-based and episodic availability, independent of mood stabilization or socioeconomic influences. Finally, alcohol and ERT appear to interact to impact both episodic and knowledge-based performance.
alcohol; moderate drinking; estrogen replacement therapy; ERT; cognition
This study aimed to examine the association between diabetes and hyperglycaemia—assessed by HbA1c—and change in cognitive function in persons with and without diabetes.
This was a prospective cohort study of 8,442 non-diabetic and 516 diabetic participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined the association of baseline categories of HbA1c with 6 year change in three measures of cognition: the digit symbol substitution test (DSST); the delayed word recall test (DWRT); and the word fluency test (WFT). Our primary outcomes were the quintiles with the greatest annual cognitive decline for each test. Logistic regression models were adjusted for demographic (age, sex, race, field centre, education, income), lifestyle (smoking, drinking) and metabolic (adiposity, blood pressure, cholesterol) factors.
The mean age was 56 years. Women accounted for 56% of the study population and 21% of the study population were black. The mean HbA1c was 5.7% overall: 8.5% in persons with and 5.5% in persons without diabetes. In adjusted logistic regression models, diagnosed diabetes was associated with cognitive decline on the DSST (OR 1.42, 95% CI 1.14–1.75, p=0.002), but HbA1c was not a significant independent predictor of cognitive decline when stratifying by diabetes diagnosis (diabetes, p trend=0.320; no diabetes, p trend=0.566). Trends were not significant for the DWRT or WFT in either the presence or the absence of diabetes.
Hyperglycaemia, as measured by HbA1c, did not add predictive power beyond diabetes status for 6 year cognitive decline in this middle-aged population. Additional work is needed to identify the non-glycaemic factors by which diabetes may contribute to cognitive decline.
Cognition; Diabetes; Epidemiology; Haemoglobin A1c
Individuals with vascular disease or risk factors have substantially higher rates of cognitive decline, yet little is known on means of maintaining cognition in this group.
We examined the relation between physical activity and cognitive decline in participants of the Women’s Antioxidant Cardiovascular Study (WACS), a cohort of women with prevalent vascular disease or ≥3 coronary risk factors. Recreational physical activity was assessed at baseline (1995–1996) and every two years thereafter. In 1998–2000, participants aged ≥65 years underwent a telephone cognitive battery including five tests of global cognition, verbal memory, and category fluency (n=2809). Tests were administered three additional times over 5.4 years. We used multivariable-adjusted generalized linear models for repeated measures to compare the annual rates of cognitive score changes across levels of total physical activity and on walking, as assessed at WACS baseline.
We found a significant trend (p-trend<0.001) of slower rates of cognitive decline with increasing energy expenditure. Compared to the bottom quintile of total physical activity, significant differences in rates of cognitive decline were observed from the fourth quintile (p=0.04 for fourth quintile, p<0.001 for fifth quintile) or the equivalent of daily 30-minute walks at a brisk pace. This difference was equivalent to the difference in cognitive decline observed for women who were younger by 5–7 years. Walking was also strongly related to slower rates of cognitive decline (p-trend=0.003).
Regular physical activity, including walking, was associated with better preservation of cognitive function in older women with vascular disease or risk factors.