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1.  Dietary fat types and 4-year cognitive change in community-dwelling older women 
Annals of Neurology  2012;72(1):124-134.
To relate dietary fat types to cognitive change in healthy community-based elders.
Among 6,183 older participants in the Women’s Health Study, we related intake of major fatty acids (FAs) (saturated [SFA], mono-unsaturated [MUFA], total poly-unsaturated [PUFA], trans-unsaturated) to late-life cognitive trajectory. Serial cognitive testing, conducted over 4 years, began 5 years post-dietary assessment. Primary outcomes were global cognition (averaging tests of general cognition, verbal memory and semantic fluency) and verbal memory (averaging tests of recall). We used analyses of response profiles and logistic regression to estimate multivariable-adjusted differences in cognitive trajectory and risk of worst cognitive change (worst 10%) by fat intake.
Higher SFA intake was associated with worse global cognitive (p-linear-trend=0.008) and verbal memory (p-linear-trend=0.01) trajectories. There was a higher risk of worst cognitive change, comparing highest vs. lowest SFA quintiles: the multivariable-adjusted odds ratio (OR) (95% confidence interval, CI) was 1.64 (1.04,2.58) for global cognition and 1.65 (1.04,2.61) for verbal memory. By contrast, higher MUFA intake was related to better global cognitive (p-linear-trend<0.001) and verbal memory (p-linear-trend=0.009) trajectories, and lower OR (95% CI) of worst cognitive change in global cognition (0.52 [0.31,0.88]) and verbal memory (0.56 [0.34,0.94]). Total fat, PUFA, and trans fat intakes were not associated with cognitive trajectory.
Higher SFA intake was associated with worse global cognitive and verbal memory trajectories, while higher MUFA intake was related to better trajectories. Thus, different consumption levels of the major specific fat types, rather than total fat intake itself, appeared to influence cognitive aging.
PMCID: PMC3405188  PMID: 22605573
2.  Plasma c-peptide levels and rates of cognitive decline in older, community-dwelling women without diabetes 
Psychoneuroendocrinology  2008;33(4):455-461.
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.
PMCID: PMC2396343  PMID: 18261857
insulin; c-peptide; diabetes; cognitive decline; aging
3.  Physical activity and cognition in women with vascular conditions 
Archives of internal medicine  2011;171(14):1244-1250.
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.
PMCID: PMC3153432  PMID: 21771894
4.  Low dose aspirin and cognitive function in the women's health study cognitive cohort 
BMJ : British Medical Journal  2007;334(7601):987.
Objective To determine whether low dose aspirin protects women aged 65 or more against cognitive decline.
Design Cohort study within both arms of the women's health study, a randomised, double blind, placebo controlled trial of low dose aspirin for the primary prevention of cardiovascular disease and cancer, 1992-5.
Setting Women's health study, 1998-2004.
Participants 6377 women aged 65 or more.
Interventions Low dose aspirin (100 mg on alternate days) or placebo for a mean of 9.6 years.
Main outcome measures Women had three cognitive assessments at two year intervals by telephone. The battery to assess cognition included five tests measuring general cognition, verbal memory, and category fluency. The primary prespecified outcome was a global score, averaging performance across all tests. The key secondary outcome was a verbal memory score, averaging performance on four measures of verbal memory.
Results At the initial assessment (mean 5.6 years after randomisation) cognitive performance in the aspirin group was similar to that of the placebo group (mean difference in global score −0.01, 95% confidence interval −0.04 to 0.02). Mean decline in the global score from the first to the final cognitive assessment was also similar in the aspirin compared with placebo groups (mean difference 0.01, −0.02 to 0.04). The risk of substantial decline (in the worst 10th centile of decline) was also comparable between the groups (relative risk 0.92, 0.77 to 1.10). Findings were similar for verbal memory; however, a 20% lower risk was observed for decline in category fluency with aspirin (relative risk 0.80, 0.67 to 0.97).
Conclusion Long term use of low dose aspirin does not provide overall benefits for cognition among generally healthy women aged 65 or more.
PMCID: PMC1867896  PMID: 17468120
5.  Prospective study of type 2 diabetes and cognitive decline in women aged 70-81 years 
BMJ : British Medical Journal  2004;328(7439):548.
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.
PMCID: PMC381043  PMID: 14980984
6.  Fasting Insulin Levels and Cognitive Decline in Older Women without Diabetes 
Neuroepidemiology  2008;30(3):174-179.
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.
PMCID: PMC2821443  PMID: 18421217
Diabetes; Insulin, cognitive performance; Aging, cognitive decline; Dementia
7.  Education and Cognitive Decline in Older Americans: Results From the AHEAD Sample 
Research on aging  2007;29(1):73-94.
Although education is consistently related to better cognitive performance, findings on the relationship between education and age-associated cognitive change have been conflicting. Using measures of multiple cognitive domains from four waves of the Asset and Health Dynamics of the Oldest Old study, a representative sample of Americans aged 70 years and older, the authors performed growth curve modeling to examine the relationships between education, initial cognitive score, and the rate of decline in cognitive function. More years of education were linked to better initial performance on each of the cognitive tests, and higher levels of education were linked to slower decline in mental status. However, more education was unrelated to the rate of decline in working memory, and education was associated with somewhat faster cognitive decline on measures of verbal memory. These findings highlight the role of early-life experiences not only in long-term cognitive performance but also in old-age cognitive trajectories.
PMCID: PMC2760835  PMID: 19830260
education; socioeconomic status; cognition; memory; growth curve modeling
8.  Formal Education Level Versus Self-Rated Literacy as Predictors of Cognitive Aging 
To compare the prediction of cognitive functioning by formal education and self-rated literacy and the differences in prediction across younger and older cohorts.
Data on 28,535 respondents were drawn from a cross-sectional representative sample of community-dwelling older individuals (≥50), participating in the Survey of Health, Ageing, and Retirement in Europe. Education level was classified according to the International Standard Classification of Education 1997 (ISCED-1997) self-rated literacy was determined by having respondents rate their reading and writing on 1–5 scales. Cognitive functioning was measured by verbal recall, word fluency, and arithmetic ability.
Structural equation modeling demonstrated that self-rated literacy was more strongly associated with cognitive functioning than was education level, with or without additional exogenous variables (age, sex, household income, medical conditions, activities of daily living, reading eyesight, and country). The association between education level and cognitive functioning was weaker in older than in younger age groups, whereas the association between self-rated literacy and cognitive functioning showed the opposite trend.
Self-rated literacy was found to be a better predictor of late-life cognitive functioning than was the level of formal education. The results have implications for studies of age-related differences in which education level is taken into account.
PMCID: PMC3636669  PMID: 22421808
Aging; Cognitive functioning; Education; Literacy; Reading and writing
9.  Caffeine and cognitive decline in elderly women at high vascular risk 
Journal of Alzheimer's disease : JAD  2013;35(2):10.3233/JAD-122371.
Persons with vascular disorders are at higher risk of cognitive decline.
To determine whether caffeine may be associated with cognitive decline reduction in elderly at high vascular risk.
We included 2475 women aged 65+ years in the Women’s Antioxidant Cardiovascular Study, a randomized trial of antioxidants and B vitamins for cardiovascular disease secondary prevention. We ascertained regular caffeine intake at baseline (1995–1996) using a validated 116 item-food frequency questionnaire. From 1998–2000 to 2005–2006, we administered four telephone cognitive assessments at two-year intervals evaluating global cognition, verbal memory and category fluency. The primary outcome was the change in global cognitive score, which was the average of the z-scores of all tests. We used generalized linear models for repeated measures that were adjusted for various sociodemographic, health and lifestyle factors to evaluate the difference in cognitive decline rates across quintiles of caffeine intake.
We observed significantly slower rates of cognitive decline with increasing caffeine intake (p-trend=0.02). The rate difference between the highest and lowest quintiles of usual caffeine intake (> 371 versus < 30 mg/day) was equivalent to that observed between those who were 7 years apart in age (p=0.006). Consumption of caffeinated coffee was significantly related to slower cognitive decline (p-trend=0.05), but not other caffeinated products (e.g., decaf, tea, cola, chocolate). We conducted interaction analyses and observed stronger associations in women assigned to vitamin B supplementation (p-interaction = 0.02).
Caffeine intake was related to moderately better cognitive maintenance over 5 years in older women with vascular disorders.
PMCID: PMC3807252  PMID: 23422357
Cognition; Aging; Caffeine; Cohort studies; Risk factors; Epidemiology
10.  Cognitive function is a risk for health literacy in older adults with diabetes 
Cognitive impairment is common in older adults with diabetes, yet it is unclear to what extent cognitive function is associated with health literacy. We hypothesized that cognitive function, independent of education, is associated with health literacy.
The sample included 537 African American, American Indian, and White men and women 60 years or older. Measures of cognitive function included the Mini-Mental State Examination (MMSE), Verbal Fluency, Brief Attention, and Digit Span Backward tests. Health literacy was assessed using the S-TOFHLA.
Cognitive function was associated with health literacy, independent of education and other important confounders. Every unit increase in the MMSE, Digit Span Backward, Verbal Fluency or Brief Attention was associated with a 20% (p<.001), 34% (p<.001), 5% (p<.01), and 16% (p<.01) increase in the odds of having adequate health literacy, respectively.
These results suggest that cognitive function is associated with health literacy in older adults with diabetes. Because poor cognitive function may undermine health literacy, efforts to target older adults on improving health literacy should consider cognitive function as a risk factor.
PMCID: PMC3742688  PMID: 23806477
cognition; health literacy; diabetes
11.  Executive Decline and Dysfunction Precedes Declines in Memory: The Women's Health and Aging Study II 
Understanding preclinical transitions to impairment in cognitive abilities associated with risks for functional difficulty and dementia. This study characterized in the Women's Health and Aging Study (WHAS) II 9-year declines and transitions to impairment across domains of cognition.
The WHAS II is an observational study of initially high-functioning, community-dwelling women aged 70–80 years at baseline. Random-effects models jointly compared rates of decline, and discrete-time Cox models estimated hierarchies of incident clinical impairment on measures of psychomotor speed and executive function (EF) using the Trail Making Test and in immediate and delayed verbal recall using the Hopkins Verbal Learning Test. Patterns of transition were related to incidence of global cognitive impairment on the Mini-Mental State Exam (MMSE).
Mean decline and impairment occurred first in EF and preceded declines in memory by about 3 years. Thereafter, memory decline was equivalent to that for EF. Over 9 years, 49% developed domain-specific impairments. Risk of incident EF impairment occurred in 37% of the sample and was often the first impairment observed (23.7%), at triple the rate for psychomotor speed (p < .01). Risk of immediate and delayed recall impairments was nearly double that for psychomotor speed (p values <.01). Incident impairment in EF and delayed recall was associated with greater risk for MMSE impairment.
Executive dysfunction developed first among nearly one quarter of older women and was associated with elevated risk for global cognitive impairment. Because EF declines preceded memory declines and are important to efficient storage and retrieval EF represents an important target for interventions to prevent declines in memory and MMSE both of which are associated with progression to dementia.
PMCID: PMC2691188  PMID: 19182230
Cognitive decline; Executive dysfunction; Memory; Cognitive impairment; Mild cognitive impairment
12.  Migraine and cognitive decline among women: prospective cohort study 
Objective To evaluate the association between migraine and cognitive decline among women.
Design Prospective cohort study.
Setting Women’s Health Study, United States.
Participants 6349 women aged 65 or older enrolled in the Women’s Health Study who provided information about migraine status at baseline and participated in cognitive testing during follow-up. Participants were classified into four groups: no history of migraine, migraine with aura, migraine without aura, and past history of migraine (reports of migraine history but no migraine in the year prior to baseline).
Main outcome measures Cognitive testing was carried out at two year intervals up to three times using the telephone interview for cognitive status, immediate and delayed recall trials of the east Boston memory test, delayed recall trial of the telephone interview for cognitive status 10 word list, and a category fluency test. All tests were combined into a global cognitive score, and tests assessing verbal memory were combined to create a verbal memory score.
Results Of the 6349 women, 853 (13.4%) reported any migraine; of these, 195 (22.9%) reported migraine with aura, 248 (29.1%) migraine without aura, and 410 (48.1%) a past history of migraine. Compared with women with no history of migraine, those who experienced migraine with or without aura or had a past history of migraine did not have significantly different rates of cognitive decline in any of the cognitive scores: values for the rate of change of the global cognitive score between baseline and the last observation ranged from −0.01 (SE 0.04) for past history of migraine to 0.08 (SE 0.04) for migraine with aura when compared with women without any history of migraine. Women who experienced migraine were also not at increased risk of substantial cognitive decline (worst 10% of the distribution of decline). When compared with women without a history of migraine, the relative risks for the global score ranged from 0.77 (95% confidence interval 0.46 to 1.28) for women with migraine without aura to 1.17 (0.84 to 1.63) for women with a past history of migraine.
Conclusion In this prospective cohort of women, migraine status was not associated with faster rates of cognitive decline.
PMCID: PMC3414433  PMID: 22875950
13.  Mediterranean diet and cognitive decline in women with cardiovascular disease or risk factors 
Cardiovascular disease and vascular risk factors increase rates of cognitive impairment, but very little is known regarding prevention in this high-risk group. The heart-healthy Mediterranean-type dietary pattern may beneficially influence both vascular and cognitive outcomes.
We examined the association between Mediterranean-style diet and cognitive decline in women with prevalent vascular disease or ≥3 coronary risk factors.
Design / Participants / Setting
Prospective cohort study among 2504 women participants of the Women’s Antioxidant Cardiovascular Study (WACS), a cohort of female health professionals Adherence to the Mediterranean diet was determined at WACS baseline (1995–1996) using a zero-to-nine-point scale with higher scores indicating higher adherence. In 1998–2000, participants aged ≥ 65 years underwent a telephone cognitive battery including five tests of global cognition, verbal memory, and category fluency. Tests were administered three additional times over 5.4 years.
Statistical analyses performed
We used multivariable-adjusted generalized linear models for repeated measures to compare the annual rates of cognitive score changes across tertiles of Mediterranean diet score, as assessed at WACS baseline.
In both basic- and multivariable-adjusted models, Mediterranean diet was not related to cognitive decline. No effect modification was detected by age, education, depression, cardiovascular disease severity at WACS baseline, or level of cognition at initial assessment.
In women at higher risk of cognitive decline due to vascular disease or risk factors, adherence to the Mediterranean diet was not associated with subsequent 5-year cognitive change.
PMCID: PMC3378990  PMID: 22709809
cognitive decline; vascular disease; hypertension; Mediterranean diet; longitudinal study
14.  Frequent Cognitive Activity Compensates for Education Differences in Episodic Memory 
To test the hypothesis that frequent participation in cognitive activities can moderate the effects of limited education on cognitive functioning.
A national study of adult development and aging, Midlife in the United States (MIDUS), with assessments conducted at the second wave of measurement in 2004-2006.
Assessments were made over the telephone (cognitive measures) and in a mail questionnaire (demographic variables, measures of cognitive and physical activity, and self-rated health).
A total of 3343 men and women between the ages of 32 and 84 with a mean age of 55.99.
The dependent variables were Episodic Memory (Immediate and Delayed Word List Recall) and Executive Functioning (Category Fluency, Backward Digit Span, Backward Counting Speed, Reasoning, and Attention Switching Speed). The independent variables were years of education and frequency of cognitive activity (reading, writing, doing word games or puzzles, and attending lectures). The covariates were age, sex, self-rated health, income, and frequency of physical activity.
The two cognitive measures were regressed on education, cognitive activity frequency, and their interaction, while controlling for the covariates. Education and cognitive activity were significantly correlated with both cognitive abilities. The interaction of education and cognitive activity was significant for episodic memory, but not for executive functioning.
Those with lower education had lower cognitive functioning, but this was qualified by level of cognitive activity. For those with lower education, engaging frequently in cognitive activities showed significant compensatory benefits for episodic memory, which has promise for reducing social disparities in cognitive aging.
PMCID: PMC2855891  PMID: 20094014
cognitive activity; education; memory; executive function; cognitive aging
15.  Does cognitive reserve shape cognitive decline? 
Annals of neurology  2011;70(2):296-304.
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.
PMCID: PMC3152621  PMID: 21563209
16.  Neighborhood Socioeconomic Context and Cognitive Decline Among Older Mexican Americans: Results From the Sacramento Area Latino Study on Aging 
American Journal of Epidemiology  2011;174(4):423-431.
In 1 previous study, it was shown that neighborhood socioeconomic disadvantage is associated with cognitive decline among Latinos. No studies have explored whether and to what extent individual-level socioeconomic factors account for the relation between neighborhood disadvantage and cognitive decline. The purpose of the present study was to assess the influence of neighborhood socioeconomic position (SEP) on cognitive decline and examine how individual-level SEP factors (educational level, annual income, and occupation) influenced neighborhood associations over the course of 10 years. Participants (n = 1,789) were community-dwelling older Mexican Americans from the Sacramento Area Latino Study on Aging. Neighborhood SEP was derived by linking the participant's individual data to the 2000 decennial census. The authors assessed cognitive function with the Modified Mini-Mental State Examination. Analyses used 3-level hierarchical linear mixed models of time within individuals within neighborhoods. After adjustment for individual-level sociodemographic characteristics, higher neighborhood SEP was significantly associated with cognitive function (β = −0.033; P < 0.05) and rates of decline (β = −0.0009; P < 0.10). After adjustment for individual educational level, neighborhood SEP remained associated with baseline cognition but not with rates of decline. Differences in individual educational levels explained most of the intra- and interneighborhood variance. These results suggest that the effect of neighborhood SEP on cognitive decline among Latinos is primarily accounted for by education.
PMCID: PMC3159426  PMID: 21715645
aging; cognition; education; Mexican Americans; residence characteristics
17.  Validation of a cognitive assessment battery administered by telephone 
While the gold standard method of cognitive assessment is a face-to-face administration, telephone-based assessments offer several advantages if they demonstrate reliability and validity.
Observational study; 110 participants randomly assigned to receive two administrations of the same cognitive test battery 6 months apart in one of four combinations (1st administration/2nd administration): telephone/telephone; telephone/face-to-face; face-to-face/telephone; or face-to-face/face-to-face.
Academic medical center
110 non-demented women between the ages of 65 and 90 years.
The battery included tests of attention, verbal learning and memory, verbal fluency, executive function, working memory and global cognitive functioning plus self-report measures of perceived memory problems, depressive symptoms, sleep disturbance and health-related quality of life. Test-retest reliability, concurrent validity, relative bias associated with telephone administration, and change scores were evaluated.
There were no statistically significant differences in scores on any of the cognitive tests or questionnaires between randomly assigned modes of administration at baseline indicating equivalence across modes. There was no significant bias for tests or questionnaires administered by telephone (ps>0.01). Nor was there a difference in mean change scores between administration modes except for the Category Fluency (p = 0.01) and the California Verbal Learning Test long delay-free recall (p < 0.01). Mean test-retest coefficients for the battery were not significantly different across groups though individual test-retest correlation coefficients were generally higher within mode than across mode.
Telephone administration of cognitive tests and questionnaires to older women is both reliable and valid. Use of telephone batteries can substantially reduce the economic cost and burden of cognitive assessments and increase enrollment, retention and data completeness thereby improving study validity.
PMCID: PMC3448122  PMID: 22985137
cognition; assessment; telephone; validation; tests
18.  Education, Income, and Incident Heart Failure in Post Menopausal Women: The Women’s Health Initiative Hormone Therapy trials 
To estimate the effect of education and income on incident heart failure (HF) hospitalization among post-menopausal women.
Investigations of socioeconomic status (SES) have focused on outcomes after HF diagnosis, not associations with incident HF. We used data from the Women’s Health Initiative Hormone Trials to examine the association between SES levels and incident HF hospitalization.
We included 26,160 healthy, post-menopausal women. Education and income were self-reported. ANOVA, Chi-square tests, and proportional hazards models were used for statistical analysis, with adjustment for demographics, co-morbid conditions, behavioral factors, and hormone and dietary modification assignments.
Women with household incomes <$20,000/year had higher HF hospitalization incidence (57.3/10,000 person-years) than women with household incomes >$50,000/year (16.7/10,000 person-years; p<0.01). Women with less than a high school education had higher HF hospitalization incidence (51.2/10,000 person-years) than college graduates and above (25.5/10,000 person-years; p<0.01). In multivariable analyses, women with the lowest income levels had 56% higher risk (HR 1.56, 95% CI 1.19 to 2.04) than the highest income women; women with the least amount of education had 21% higher risk for incident HF hospitalization (HR 1.21, 95% CI 0.90 to 1.62) than the most educated women.
Lower income is associated with an increased incidence of HF hospitalization among healthy, post-menopausal women, whereas multivariable adjustment attenuated the association of education with incident HF.
PMCID: PMC3635103  PMID: 21939829
heart failure; socioeconomic status; women
19.  Information Processing Speed and 8-Year Mortality Among Community-Dwelling Elderly Japanese 
Journal of Epidemiology  2014;24(1):52-59.
Cognitive function is an important contributor to health among elderly adults. One reliable measure of cognitive functioning is information processing speed, which can predict incident dementia and is longitudinally related to the incidence of functional dependence. Few studies have examined the association between information processing speed and mortality. This 8-year prospective cohort study design with mortality surveillance examined the longitudinal relationship between information processing speed and all-cause mortality among community-dwelling elderly Japanese.
A total of 440 men and 371 women aged 70 years or older participated in this study. The Digit Symbol Substitution Test (DSST) was used to assess information processing speed. DSST score was used as an independent variable, and age, sex, education level, depressive symptoms, chronic disease, sensory deficit, instrumental activities of daily living, walking speed, and cognitive impairment were used as covariates.
During the follow-up period, 182 participants (133 men and 49 women) died. A multivariate Cox proportional hazards model showed that lower DSST score was associated with increased risk of mortality (hazard ratio [HR] = 1.62, 95% CI = 0.97–2.72; HR = 1.73, 95% CI = 1.05–2.87; and HR = 2.55, 95% CI = 1.51–4.29, for the third, second, and first quartiles of DSST score, respectively).
Slower information processing speed was associated with shorter survival among elderly Japanese.
PMCID: PMC3872525  PMID: 24240629
all-cause mortality; cognition; community elderly; information processing speed
20.  Sex Differences in the Association of Framingham Cardiac Risk Score with Cognitive Decline in Community-Dwelling Elders without Clinical Heart Disease 
Psychosomatic medicine  2011;73(8):683-689.
To investigate a possible link between cardiovascular risk factors and age-related cognitive decline, the association of the 1998 Framingham Cardiac Risk Score (FCRS) with the trajectory of cognitive function test (CFT) performance over 18 years was examined in adults 50 years and older without clinical heart disease at baseline.
Participants were 985 men and women who had assessments of cognitive function at three to four year intervals. The association of FCRS category with CFT score trajectory was examined using mixed effect models stratified by sex and controlling for age, education, and number of repeat cognitive assessments.
At baseline, median FCRS corresponded to a 14% risk of a CHD event within 10 years for men and a 8% risk for women; 31% of men and 6% of women were at high (>20%) risk. In longitudinal analyses, women with FCRS risk >7% had a higher rate of decline on tests of verbal fluency (p’s <.05) and long term recall (p’s <.01) compared to low risk women; modest, but significant (p’s <.05), differences in the trajectory of MMSE and Trails B scores were also apparent. FCRS category was not related to the rate of decline in CFT performance in men.
For older women, very low levels of CHD risk were associated with preservation of cognitive function over 10 years, suggesting that maintenance of cardiovascular health may slow cognitive decline. The minimal association in men, who were at higher baseline risk, may be due to selective attrition of men with greater cognitive decline.
PMCID: PMC3188670  PMID: 21949428
aging; cardiovascular; cognitive function; prospective
21.  Vitamin E, vitamin C and β-carotene and cognitive function among women with or at risk of cardiovascular disease: the WACS study 
Circulation  2009;119(21):2772-2780.
Cardiovascular factors are associated with cognitive decline. Antioxidants may be beneficial.
The Women’s Antioxidant Cardiovascular Study was a trial of vitamin E (402 mg every other day), β-carotene (50 mg every other day) and vitamin C (500 mg daily) for the secondary prevention of cardiovascular disease (CVD). From 1995–1996, women 40+ years, with CVD or ≥3 coronary risk factors were randomized. From 1998–1999, a cognitive function substudy was initiated among 2824 participants aged 65+ years. With 5 cognitive tests, cognition was assessed by telephone four times over 5.4 years. The primary outcome was a global composite score averaging all scores; repeated measures analyses were used to examine cognitive change over time.
Vitamin E and β-carotene supplementation were not associated with slower rates of cognitive change (mean difference in change for vitamin E versus placebo = −0.01, 95% CI −0.05, 0.04, p=0.78; for β-carotene=0.03, 95% CI −0.02, 0.07, p=0.28). Although vitamin C supplementation was associated with better performance at the last assessment (mean difference = 0.13, 95% CI 0.06, 0.20, p=0.0005), it was not associated with cognitive change over time (mean difference in change = 0.02, 95% CI −0.03, 0.07, p=0.39). Vitamin C was more protective against cognitive change among those with new cardiovascular events during the trial (p-interaction= 0.009).
Antioxidant supplementation did not slow cognitive change among women with preexisting CVD or CVD risk factors. A possible late effect of vitamin C or of β-carotene among those with low dietary intake on cognition warrant further study.
PMCID: PMC2752297  PMID: 19451353
22.  Baseline Serum Cholesterol Is Selectively Associated With Motor Speed and Not Rates of Cognitive Decline: The Women's Health and Aging Study II 
Background. Although several studies have investigated the association between cholesterol and dementia, few have examined cholesterol and decline across cognitive domains. We examined serum total and high-density lipoprotein (HDL) cholesterol, total-to-HDL ratio, and trajectories across cognitive domains.
Methods. Participants were 436 community-residing women (70–79 years old) in the Women's Health and Aging Study II; they were screened to be physically high-functioning and cognitively intact at baseline. Cognition and other health-related variables were assessed at five intervals spanning 9 years. Cognitive assessments included Trail Making Test Parts A (TMT-A) and B (TMT-B), Hopkins Verbal Learning Test-Revised, Purdue Pegboard, and Mini-Mental State Examination (MMSE). The association between baseline levels of serum lipids and cognitive trajectories were evaluated using Generalized Estimating Equations (GEE). Covariates included age, education, race, vascular disease, serum creatinine, depression, and lipid-lowering medications.
Results. In multivariate analyses, baseline higher total (p =.02) and HDL (p =.03) cholesterol were associated with better performance on the Purdue Pegboard. Using clinical cholesterol cutoffs, baseline serum total cholesterol levels >240 mg/dL were associated with the best performance (p =.02). Baseline lipids were not associated with any other cognitive tests; there were no Lipid × Time interactions.
Conclusion. Higher baseline serum lipid levels predicted better performance over time on a measure of motor speed, but not memory or psychomotor or executive functioning in this population of elderly women. This association suggests that peripheral cholesterol levels, measured in late-life, may not be a good predictor of subsequent cognitive decline. Future research examining peripheral cholesterol over the life span and its relationship with cognition is needed.
PMCID: PMC3304295  PMID: 18559637
Cholesterol; Cognition; Motor speed; Biological aging
23.  Characteristics of hormone therapy, cognitive function, and dementia: the prospective 3C Study 
Neurology  2009;73(21):1729-1737.
To examine the association between hormone therapy (HT) and cognitive performance or dementia, focusing on the duration and type of treatment used, as well as the timing of initiation of HT in relation to the menopause.
Women 65 years and older were recruited in France as part of the Three City Study. At baseline and 2 and 4 year follow-up, women were administered a short cognitive test battery and a clinical diagnosis of dementia was made. Detailed information was also gathered relating to current and past HT use. Analysis was adjusted for a number of socio-demographic, behavioural, physical and mental health variables, as well as Apolipoprotein ε4 (Apoe-ε4).
Among 3130 naturally postmenopausal women, current HT users performed significantly better than never users on verbal fluency, working memory and psychomotor speed. These associations varied according to the type of treatment and a longer duration of HT appeared to be more beneficial. However, initiation of HT close to the menopause was not associated with better cognition. HT did not significantly reduce dementia risk over 4 years but current treatment diminished the negative effect associated with Apoe-ε4.
Current HT was associated with better performance in certain cognitive domains but these associations are dependent on the duration and type of treatment used. We found no evidence that HT needs to be initiated close to the menopause to have a beneficial effect on cognitive function in later life. Current HT may decrease the risk of dementia associated with the Apoe-ε4 allele.
PMCID: PMC2993903  PMID: 19933973
Aged; Aged, 80 and over; Apolipoproteins E; genetics; Cognition Disorders; drug therapy; etiology; genetics; Cohort Studies; Dementia; complications; genetics; Estrogen Replacement Therapy; methods; Female; Humans; Logistic Models; Neuropsychological Tests; Retrospective Studies
24.  Resistance Training and Executive Functions: A 12-Month Randomised Controlled Trial 
Archives of internal medicine  2010;170(2):170-178.
Cognitive decline among seniors is a pressing health care issue. Specific exercise training may combat cognitive decline. We compared the effect of once-weekly and twice-weekly resistance training with twice-weekly balance and tone exercise training on the performance of executive cognitive functions in senior women.
In this single-blinded randomised trial, 155 community-dwelling women aged 65 to 75 years old living in Vancouver, Canada were randomly allocated to once-weekly resistance training (n=54), twice-weekly resistance training (n=52), or to twice-weekly balance and tone training (i.e., control group) (n=49). Primary outcome measure was performance on the Stroop Test, an executive cognitive test of selective attention and conflict resolution. Secondary outcomes of executive cognitive functions included set shifting as measured by the Trail Making Tests (Part A & B) and working memory as assessed by verbal digits forward and backward tests. Gait speed, muscular function, and whole brain volume were also secondary outcome measures.
Both resistance training groups significantly improved their performance on the Stroop Test compared with those in the balance and tone group (p≤0.03). Specifically, task performance improved by 12.6% and 10.9% in the once-weekly and twice-weekly resistance training groups respectively; it deteriorated by 0.5% in the balance and tone group. Enhanced selective attention and conflict resolution was significantly associated with increased gait speed. Also, both resistance training groups demonstrated reductions in whole brain volume compared with the balance and tone group at the end of the study (p≤0.03).
Twelve months of once-weekly or twice-weekly resistance training benefited the executive cognitive function of selective attention and conflict resolution among senior women.
TRIAL REGISTRATION Identifier: NCT00426881
PMCID: PMC3448565  PMID: 20101012 CAMSID: cams2304
Resistance Training; Executive Functions; Older Adults
25.  Lipid lowering agents, cognitive decline, and dementia: the three-city study 
Journal of Alzheimer's Disease  2012;30(3):629-637.
The aim of this prospective cohort study was to evaluate the effects of lipid lowering agent (LLA) intake on cognitive function in 6830 community-dwelling elderly persons. Cognitive performance (global cognitive functioning, visual memory, verbal fluency, psychomotor speed and executive function), clinical diagnosis of dementia, and fibrate and statin use, were evaluated at baseline, and 2, 4, and 7 year follow-up. Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics, mental and physical health including vascular risk factors, and genetic vulnerability (apolipoprotein E and cholesteryl ester transfer protein). For women but not men, fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only (HR=1.29, 95%CI=1.09–1.54, p=0.004), and did not increase risk for incident dementia. This association was independent of genetic vulnerability related to ApoE and Cholesteryl Exchange Transfer Protein polymorphisms and occurred only in women with higher LDL-cholesterol levels and treated with fibrate (HR=1.39, 95%CI=1.08–1.79, p=0.01) and not in those with lower LDL-cholesterol levels irrespective of fibrate treatment. For both sexes, no significant associations were found between statins (irrespective of their lipophilicity) and either cognitive decline or dementia incidence. This prospective study, adjusting for multiple confounders, found no evidence that LLA given in late life reduced the risk of cognitive decline and dementia, but did raise the possibility that women with treatment-resistant high LDL-cholesterol may be at increased risk of decline in visual memory.
PMCID: PMC3743740  PMID: 22451317
Fibrate; Statin; Cognitive aging; Alzheimer's disease; Elderly; Apolipoprotein E; Cholesteryl Exchange Transfer Protein; Prospective cohort.

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