Ginkgo Evaluation Of Memory Study Research Articles

An assessment of the mediating role of hypertension in the effect of long-term air pollution exposure on dementia.

Growing evidence links air pollution exposure to the risk of dementia. We hypothesized that hypertension may partially mediate this effect. We previously documented an association between air pollution and dementia in the Ginkgo Evaluation of Memory Study, a randomized, placebo-controlled trial of 3069 adults ≥75 years across four US sites who were evaluated for dementia every 6 months from 2000-2008. We utilized a two-stage regression approach for causal mediation analysis to decompose the total effect of air pollution on dementia into its natural direct and indirect effect through prevalent hypertension. Exposure to air pollution in the 10 or 20 years before enrollment was assigned using estimates from fine-scale spatial-temporal models for PM2.5, PM10, and NO2. We used Poisson regression models for hypertension and Cox proportional hazard models for time-to-incident all-cause dementia, adjusting for a priori confounders. Participants were free of mild cognitive impairment at baseline (n = 2564 included in analyses); 69% had prevalent hypertension at baseline. During follow-up, 12% developed all-cause dementia (Alzheimer's disease [AD] = 212; vascular dementia with or without AD [VaD/AD mixed] = 97). We did not find an adverse effect of any air pollutant on hypertension. Hypertension was associated with VaD/AD mixed (HR, 1.92 [95% CI = 1.14, 3.24]) but not AD. We did not observe mediation through hypertension for the effect of any pollutant on dementia outcomes. The lack of mediated effect may be due to other mechanistic pathways and the minimal effect of air pollution on hypertension in this cohort of older adults.

The impact of falls on activities of daily living in older adults: A retrospective cohort analysis.

Falls contribute to impairments in activities of daily living (ADLs), resulting in significant declines in the quality of life, safety, and functioning of older adults. Understanding the magnitude and duration of the effect of falls on ADLs, as well as identifying the characteristics of older adults more likely to have post-fall ADL impairment is critical to inform fall prevention and post-fall intervention. The purpose of this study is to 1) Quantify the association between falls and post-fall ADL impairment and 2) Model trajectories of ADL impairment pre- and post-fall to estimate the long-term impact of falls and identify characteristics of older adults most likely to have impairment. Study participants were from the Ginkgo Evaluation of Memory Study, a randomized controlled trial in older adults (age 75+) in the United States. Self-reported incident falls and ADL scores were ascertained every 6 months over a 7-year study period. We used Cox proportional hazards analyses (n = 2091) to quantify the association between falls and ADL impairment and latent class trajectory modeling (n = 748) to visualize trajectories of ADL impairment pre-and post-fall. Falls reported in the previous 6 months were associated with impairment in ADLs (HR: 1.42; 95% CI 1.32, 1.52) in fully adjusted models. Based on trajectory modeling (n = 748), 19% (n = 139) of participants had increased, persistent ADL impairment after falling. Participants who were female, lived in a neighborhood with higher deprivation, or experienced polypharmacy were more likely to have ADL impairment post-fall. Falls are associated with increased ADL impairment, and this impairment can persist over time. It is crucial that all older adults, and particularly those at higher risk of post-fall ADL impairment have access to comprehensive fall risk assessment and evidence-based fall prevention interventions, to help mitigate the negative impacts on ADL function.

Baseline Frailty and Domain‐specific Cognitive Declines in Healthy and MCI Older Adults

AbstractBackgroundBoth physical frailty and cognitive decline increase with age and each place adults at elevated risk for loss of independence. Inconsistent associations have been found between frailty and risk for cognitive declines across cognitive domains. However, most studies were cross‐sectional and did not include a comprehensive battery of neuropsychological tests. We hypothesized that frail older adults, whether with or without Mild Cognitive Impairment (MCI) at baseline, are at risk for accelerated domain‐specific cognitive declines.MethodThe Ginkgo Evaluation of Memory Study (GEMS) was a prospective study of 3069 dementia‐free older adults aged 72‐96 years, followed for up to 7.5 years or a diagnosis of dementia, 482 of whom were diagnosed with MCI at baseline. A modified physical frailty phenotype was constructed using GEMS baseline data. A Neuropsychological Battery consisted of 13 tests reflecting global cognition, memory, visual‐spatial construction, language, psychomotor speed/attention, and executive function were administered annually. Linear random effects models were used to compare differences in baseline and rate of change in domain scores among individuals with and without baseline frailty.ResultOverall, frail participants showed poorer baseline cognitive function in all domains, and greater declines in all cognitive domains. When stratified by baseline MCI, among non‐MCI participants, those with frailty revealed poorer baseline psychomotor speed/attention and executive function, and greater declines in all cognitive domains. Among MCI participants, those with frailty exhibited lower baseline visual‐spatial construction, and greater declines in all cognitive domains except for visual‐spatial construction and executive function. In all cognitive domains, the estimated effect of frailty on cognitive decline was greater in MCI participants than non‐MCI participants.ConclusionFrailty was predictive of accelerated cognitive declines across domains and more so in those with baseline MCI. The results from this study highlight the importance of assessing frailty as a risk factor for accelerated cognitive declines, particularly among those at elevated preclinical cognitive risk. These individuals may be at the greatest risk of transitioning to dementia.

An Examination of the Joint Effect of the Social Environment and Air Pollution on Dementia Among US Older Adults.

This study draws from the Ginkgo Evaluation of Memory Study. Participants aged 75 years and older were enrolled between 2000 and 2002 and evaluated for dementia semi-annually through 2008. Long-term exposure to particulate matter and nitrogen dioxide was assigned from spatial and spatiotemporal models. Census tract-level measures of the social environment and individual measures of social activity were used as measures of the social environment. We generated Cox proportional hazard models with census tract as a random effect and adjusted for demographic and study visit characteristics. Relative excess risk due to interaction was estimated as a qualitative measure of additive interaction. This study included 2,564 individuals. We observed associations between increased risk of dementia and fine particulate matter (µg/m3), coarse particulate matter (µg/m3), and nitrogen dioxide (ppb); HRs per 5 unit increase were 1.55 (1.01, 2.18), 1.31 (1.07, 1.60), and 1.18 (1.02, 1.37), respectively. We found no evidence of additive interaction between air pollution and the neighborhood social environment. We found no consistent evidence to suggest a synergistic effect between exposure to air pollution and measures of the social environment. Given the many qualities of the social environment that may reduce dementia pathology, further examination is encouraged.

Change in gait speed and fall risk among community-dwelling older adults with and without mild cognitive impairment: a retrospective cohort analysis

BackgroundAlthough slow gait speed is an established risk factor for falls, few studies have evaluated change in gait speed as a predictor of falls or considered variability in effects by cognitive status. Change in gait speed may be a more useful metric because of its potential to identify decline in function. In addition, older adults with mild cognitive impairment are at an elevated risk of falls. The purpose of this research was to quantify the association between 12-month change in gait speed and falls in the subsequent 6 months among older adults with and without mild cognitive impairment.MethodsFalls were self-reported every six months, and gait speed was ascertained annually among 2,776 participants in the Ginkgo Evaluation of Memory Study (2000–2008). Adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for fall risk relative to a 12-month change in gait speed.ResultsSlowing gait speed over 12 months was associated with increased risk of one or more falls (HR:1.13; 95% CI: 1.02 to 1.25) and multiple falls (HR:1.44; 95% CI: 1.18 to 1.75). Quickening gait speed was not associated with risk of one or more falls (HR 0.97; 95% CI: 0.87 to 1.08) or multiple falls (HR 1.04; 95% CI: 0.84 to 1.28), relative to those with a less than 0.10 m/s change in gait speed. Associations did not vary by cognitive status (pinteraction = 0.95 all falls, 0.25 multiple falls).ConclusionsDecline in gait speed over 12 months is associated with an increased likelihood of falls among community-dwelling older adults, regardless of cognitive status. Routine checks of gait speed at outpatient visits may be warranted as a means to focus fall risk reduction efforts.

Air pollution and plasma amyloid beta in a cohort of older adults: Evidence from the Ginkgo Evaluation of Memory study

Air pollution has been linked to Alzheimer’s disease and related dementias (ADRD), but the mechanisms connecting air pollution to ADRD have not been firmly established. Air pollution may cause oxidative stress and neuroinflammation and contribute to the deposition of amyloid beta (Aβ) in the brain. We examined the association between fine particulate matter<2.5 μm in diameter (PM2.5), particulate matter<10 μm in diameter (PM10), nitrogen dioxide (NO2), and plasma based measures of Aβ1-40, Aβ1-42 and Aβ1-42/Aβ1-40 using data from 3044 dementia-free participants of the Ginkgo Evaluation of Memory Study (GEMS). Air pollution exposures were estimated at residential addresses that incorporated address histories dating back to 1980, resulting in one-, five-, 10- and 20- year exposure averages. Aβ was measured at baseline (2000–2002) and then again at the end of the study (2007–2008) allowing for linear regression models to assess cross-sectional associations and linear random effects models to evaluate repeated measures. After adjustment for socio-demographic and behavioral covariates, we found small positive associations between each air pollutant and Aβ1-40 but no association with Aβ1-42 or the ratio measures in cross sectional analysis. In repeat measures analysis, we found larger positive associations between each air pollutant and all three outcomes. We observed a 4.43% (95% CI 3.26%, 5.60%) higher Aβ1-40 level, 9.73% (6.20%, 13.38%) higher Aβ1-42 and 1.57% (95% CI: 0.94%, 2.20%) higher Aβ1-42/Aβ1-40 ratio associated with a 2 µg/m3 higher 20-year average PM2.5. Associations with other air pollutants were similar. Our study contributes to the broader evidence base on air pollution and ADRD biomarkers by evaluating longer air pollution exposure averaging periods to better mimic disease progression and provides a modifiable target for ADRD prevention.

Air pollution and dementia in older adults in the Ginkgo Evaluation of Memory Study.

Growing evidence implicates air pollution as a risk factor for dementia, but prior work is limited by challenges in diagnostic accuracy and assessing exposures in the decades prior to disease development. We evaluated the impact of long-term fine particulate matter (PM2.5 ) exposures on incident dementia (all-cause, Alzheimer's disease [AD], and vascular dementia [VaD]) in older adults. A panel of neurologists adjudicated dementia cases based on extensive neuropsychological testing and magnetic resonance imaging. We applied validated fine-scale air pollutant models to reconstructed residential histories to assess exposures. An interquartile range increase in 20-year PM2.5 was associated with a 20% higher risk of dementia (95% confidence interval [CI]: 5%, 37%) and an increased risk of mixed VaD/AD but not AD alone. Our findings suggest that air pollutant exposures over decades contribute to dementia and that effects of current exposures may be experienced years into the future.

Evaluating the importance of historical address histories in an air pollution and dementia study

AbstractBackgroundEvidence linking long‐term air pollutant exposures with dementia‐related risks is increasing. Changes in the brain may occur decades before diagnosis, and studies assessing the effects of air pollution on dementia should account for participant residential history to reduce exposure misclassification. Using the Ginkgo Evaluation of Memory Study (GEMS), we evaluated cumulative PM2.5 and NO2 exposure on dementia risk both with and without historical residential addresses.MethodGEMS was a randomized trial of 3,069 participants in Hagerstown MD, Pittsburgh PA, Sacramento CA, and Winston‐Salem NC from 2000‐2008. Residential historical addresses were obtained through LexisNexis, a company constructing address histories from public databases. PM2.5 (1980‐1999) and NO2 (1990‐1999) cumulative exposures were calculated for each participant from a spatio‐temporal model in two ways: 1) using residential address histories reconstructed from LexisNexis addresses from 1980‐1999 (Figure 1), and 2) assuming participants lived from 1980‐1999 at the address documented during the GEMS baseline visit (2000‐2002). Hazard ratios from Cox models of all‐cause dementia, Alzheimer’s disease (AD), and mixed vascular dementia (VaD/AD) were compared across both sets of cumulative PM2.5 and NO2 estimates. Models were adjusted for age, study site, randomization year, gender, treatment group, neighborhood deprivation index (NDI), education, smoking status, smoking pack years, passive smoking exposure and apolipoprotein E4 (APOE4) status.ResultHazard ratios based on the LexisNexis historical addresses were generally larger than those from analyses without residential histories (Figure 2). The largest attenuation in effect after eliminating address history was for participants with vascular dementia either with or without AD (VaD/AD). An approximate interquartile range (IQR; 3 µg/m3) increase in 10 year mean NO2 exposure was associated with a 39% (95% CI: 7%, 81%) greater risk of mixed VaD/AD, but this decreased to 25% (95% CI: ‐7%, 66%) without histories. Similarly, an IQR (2 µg/m3) increase in 20 year PM2.5 was associated with a 19% (95% CI: 4%, 36%) greater risk of all cause dementia compared to 14% (95% CI:‐1%, 31%) without the historical addresses.ConclusionFor epidemiological studies aiming to quantify long term place‐based exposures related to dementia risk, utilizing residential address databases may reduce misclassification in exposure assignments.

Plasma antioxidants and phospholipids and brain imaging biomarkers among non‐demented older adults

AbstractBackgroundPrevious studies have linked dietary fatty acids and antioxidants to dementia risk and cognitive decline. The relationships of objective markers of fatty acid and antioxidant intakes with brain imaging biomarkers remain uncertain.MethodWe assessed the associations of antioxidants and phospholipids in plasma, collected in 2000‐2002, with brain amyloid‐ß deposition on PET scans and hippocampal and white matter lesion volume on MRIs in 2009 among 193 participants of the Ginkgo Evaluation of Memory Study who were free of clinical dementia. We used multivariable‐adjusted and inverse‐probability‐weighted robust linear regression models. We measured antioxidants by organic phase extraction followed by chromatographic analysis and individual plasma phospholipids (as a percentage of total plasma phospholipid fatty acids) by gas chromatography with flame ionization detection.ResultA total of 20 participants (10%) had mild cognitive impairment at baseline and 134 participants (69%) used either multivitamin, vitamin A or β‐carotene, or vitamin E supplements (Table 1). Higher plasma retinol,α‐tocopherol, and total vitamin E were related to higher future amyloid‐ß deposition (Table 2). Higher α‐tocopherol and total vitamin E were also related to less white matter lesion volume. Carotenoids were not significantly related to any of the brain imaging biomarkers.Higher concentrations of the saturated fatty acid margaric acid (17:0) were associated with more amyloid‐ß deposition (adjusted difference per 1 SD higher margaric acid: 0.10 standardized uptake value ratio; 95% CI: 0.02, 0.19) and smaller hippocampal volume (Table 3). In contrast, higher concentrations of the saturated fatty acid behenic acid (22:0) were associated with less white matter lesion volume. Higher oleic acid (18:1n‐9c, a major monounsaturated fatty acid), was related to more hippocampal volume. Higher concentrations of the n‐3 polyunsaturated fatty acid docosahexaenoic acid (22:6n‐3c) were associated with more amyloid‐ß deposition, while higher concentrations of linoleic acid (18:2n‐6cc; a major n‐6 polyunsaturated fatty acid) were associated with less amyloid‐ß deposition (adjusted difference per 1 SD higher linoleic acid: ‐0.10 standardized uptake value ratio; 95% CI:‐0.19, ‐0.01).ConclusionSpecific antioxidants and phospholipids may be associated with brain imaging biomarkers, a hypothesis that requires formal testing in long‐term intervention studies and that represents a possible preventive intervention,

Associations between long‐term air pollution exposure and plasma amyloid beta in very old adults

AbstractBackgroundAnimal studies suggest associations between exposure to air pollutants and increased amyloid beta (Aβ) pathology. However, there is limited research evaluating the relationship of air pollution to Aβ levels in human populations. Therefore, this study examined the role of long‐term air pollution exposure in plasma amyloid levels in a US cohort of older adults.MethodThis cross‐sectional study included participants from the Ginkgo Evaluation of Memory Study, a longitudinal cohort of older adults (aged 75 years and older) recruited from four US communities who were dementia free at baseline. Plasma Aβ1‐40 levels were measured in 2000‐2002 and again in 2007‐2008 and log transformed for analyses. We applied validated fine‐scale spatiotemporal models to estimate fine particulate matter (PM2.5), coarse particles (PM10) and nitrogen dioxide (NO2) at participant residential addresses. Address history was constructed up to 20 years prior to visit dates using LexisNexis, a commercial credit reporting company. Exposure to air pollutants was averaged over multiple time periods (from one to 20 years) prior to plasma collection. We estimated percent differences (95% CIs) from ordinary least squares and linear mixed‐effect regression models for baseline and repeated measures data, respectively. All models were adjusted for age, race, gender, site, education, treatment, cystatin c, neighborhood deprivation index, alcohol intake, smoking status, pack‐years of smoking, passive smoke exposure and gait speed.ResultThis study included 3,029 participants with measured Aβ1‐40. A 3 µg/m3 (interquartile range (IQR)) higher PM10 over 10 years was associated with higher levels of Aβ1‐40 at baseline: percent difference 1.80% (95% CI: 0.22%, 3.40%). We also observed a positive association of increased magnitude in repeated measures analyses: percent difference 5.20% (95% CI: 3.69%, 6.72%). Similar associations between PM2.5 (IQR = 2 µg/m3) and NO2 (IQR = 7 ppb) and Aβ1‐40 were found in repeated measures analyses. Findings from other pollutants and exposure periods are presented in Figure 1.ConclusionThese findings provide some of the first epidemiologic evidence suggesting long‐term concentrations of PM2.5, PM10 and NO2 are associated with increased Aβ1‐40.

The impact of greenspace and air pollution exposure on incident dementia in the Ginkgo Evaluation of Memory Study

BACKGROUND AND AIM: While long term exposure to fine particulate matter (PM₂.₅) has been linked to all-cause dementia, less is known about potential modification of these effects by greenspace exposure. METHODS: The Ginkgo Evaluation of Memory Study (GEMS) was a randomized trial in four US sites (Hagerstown MD, Pittsburgh PA, Sacramento CA, and Winston-Salem NC) from 2000-2008 with rigorous neuropsychological assessments for dementia every six months. Minimum age at enrollment was 75 years. Mean residence-specific PM₂.₅ concentrations were estimated using a novel spatiotemporal model and reconstructed from residential address histories for a 20-year period (1980-1999). Greenspace exposure was measured by averaging standardized 1) normalized difference vegetation index (NDVI), 2) reverse coded distance to nearest park, and 3) percentage of park overlap within a 10km buffer of residence. We evaluated modification by greenspace of the effects of PM₂.₅ on dementia risk by including an interaction term in Cox proportional hazards models adjusted for age, study site, year of randomization, gender, treatment assignment, neighborhood deprivation index, and education. RESULTS:For 2,549 participants who were free of mild cognitive impairment (MCI) at enrollment, preliminary analyses indicate that an interquartile range (2 µg/m³) increase in 20-yr mean PM₂.₅ exposure was associated with a 19% (HR: 1.19: CI: 1.04, 1.37) greater risk of dementia. Relative to participants in the first tertile of greenspace, those in the second tertile had a 17% reduction (HR: 0.83; 95% CI: 0.63, 1.09) in dementia risk and those in the third tertile had a 25% reduction (HR: 0.75; 95% CI: 0.54, 1.03); however, these estimates included the null. Greenspace exposure did not modify the impact of PM₂.₅ on dementia risk (interaction term p-value=0.57). CONCLUSIONS:Greenspace exposure may be a promising protective factor against dementia but does not appear to modify the impact of PM₂.₅ on dementia in this cohort of older adults. KEYWORDS: Greenspace, Air pollution, All-cause dementia, Fine particulate matter, Long-term exposure

Air pollution and plasma amyloid beta: Evidence from the Ginkgo Evaluation of Memory Study

BACKGROUND AND AIM: Accumulation of amyloid beta (Aβ) proteins are central to the development of Alzheimer’s disease (AD). Air pollution has also been implicated in AD through its potential to cause neuroinflammation, microglia activation and white matter abnormalities. To date, few epidemiologic studies have examined the association between air pollution and Aβ. METHODS: The Ginkgo Evaluation of Memory Study (GEMS) is a longitudinal study of adults age 75 and older recruited from four US sites. Fine particulate matter (PM2.5), coarse particles (PM10) and nitrogen dioxide (NO2) were predicted from a national universal kriging model which estimated annual average pollutant levels at participant’s address one, five, 10 and 20 years prior to baseline visit. Both Aβ 1-40 and Aβ 1-42 were measured at baseline (years 2000-2002) and then again in 2008 in plasma blood samples using ELISA. After using multiple imputation by chained equations to impute missing covariates, we modelled baseline Aβ 1-40 and Aβ 1-42 separately using linear regression models and repeat measures (i.e., pooled) data using multilevel models with random intercepts. Final models were adjusted for several socio-demographic and behavioral covariates as well as cystatin C and apolipoprotein E ε4 carrier status. RESULTS:Pooled analyses included 4650 observations on 3004 participants. An interquartile range (IQR, 2-µg/m3) higher 5-year average PM2.5 was associated with a 4.9% higher Aβ 1-40 (95% CI: 3.6%, 6.3%) and a 10.9% higher Aβ 1-42 level (95% CI: 6.7%, 15.2%). A 7 ppb (one IQR) higher 5-year averaged NO2 was associated with a 10% higher Aβ 1-40 (95% CI: 7.7%, 12.4%) and 17.8% higher Aβ 1-42 level (95% CI: 10.4%, 25.7%). Similar results were seen for other pollutant-biomarker associations, although analysis of baseline Aβ data found attenuated results. CONCLUSIONS:Findings suggest a robust association between PM2.5, PM10 and NO2 and both plasma Aβ 1-40 and Aβ 1-42. KEYWORDS: air pollution, fine particulate matter, dementia, amyloid beta, Alzheimer's Disease

Chronic exposure to air pollution and cognitive decline in older adults

BACKGROUND AND AIM: Growing epidemiologic evidence suggests chronic exposure to fine particulate matter (PM2.5) increases risk of dementia in older adults. Despite this, studies of cognitive impairment, a prodromal sign of dementia, report inconsistent results. Studying repeated measures of cognitive function, rather than measures at a single time point, may be a more robust metric of cognitive outcomes because the study design adjusts for time-fixed confounders that affect air pollution exposure and performance on cognitive tests. Therefore, we examined the effect of air pollution on cognitive decline in a U.S. cohort of older adults. METHODS: This analysis draws from the Ginkgo Evaluation of Memory Study, a clinical trial aimed at understanding dementia prevention. Participants aged 75 years and older were enrolled between 2000 and 2002 and completed a neuropsychological battery of 10 tests repeated annually for up to eight years. Tests examined domains of memory, visuospatial abilities, language, attention, and executive function. Chronic exposure (20 years before baseline) to PM2.5 was estimated using annual averages from fine-scale spatiotemporal models and accounted for residential mobility. Trajectories of cognitive function across levels of PM2.5 were compared using generalized estimating equation regression models to account for correlations among repeated cognitive scores. Models included demographic and socioeconomic characteristics as covariates. RESULTS:This study included 2,587 individuals (mean age=78 years) free of mild cognitive impairment at baseline. Chronic exposure to PM2.5 was associated with lower overall scores of memory and visuospatial abilities. Increased exposure to PM2.5 was not associated with declines in either domain. Associations with language, attention, and executive function will be assessed in future analyses. CONCLUSIONS:This study provides support for associations between increased exposure to particulate matter and worse memory and visuospatial abilities. However, preliminary findings show no association between increased exposure and cognitive decline. KEYWORDS: Air pollution, epidemiology, neurodegenerative outcomes

Risk of Dementia Differs Across Lifestyle Engagement Subgroups: A Latent Class and Time-to-Event Analysis in Community-Dwelling Older Adults.

Better understanding of the lifestyle activities shared among older adult subgroups may inform further health behavioral interventions that can be deployed at the group or community level. We applied latent class analysis to characterize qualitatively distinct lifestyle engagement groups, examined their differential risk of incident dementia, and compared their predictive utility to traditional activity frequency and variety scores. Participants were from the Ginkgo Evaluation of Memory Study (N = 3,068, mean age = 78.5). Lifestyle activities were measured at baseline using the Lifestyle Activity Questionnaire. All-cause dementia was screened every 6 months and cases were clinically adjudicated. Median follow-up was 6 years. Time to dementia was assessed using discrete-time proportional hazards models, adjusted for demographic and health covariates. Latent classes provided slightly poorer case discrimination than the frequency scores but identified distinct qualitative subgroups. In the 4-class model, the Variety (22%) and Intellectual (18%) lifestyle groups had high engagement in intellectual activities, whereas the Variety and Social groups (32%) had high engagement in formal social activities. Compared to the Least Active group (28%), the Variety (hazard ratio [HR] = 0.67, 95% confidence interval [CI]: 0.48, 0.93) and Intellectual (HR = 0.65, 95% CI: 0.45, 0.93) groups had significantly lower risk of incident dementia, but only among those without prevalent mild cognitive impairment. Older adults highly engaged in intellectual activities, but not necessarily social activities, had the lowest risk of incident dementia. Activity frequency scores provided only slightly better case discrimination than activity variety scores and latent classes. Latent classes of older adults differed by their amount and types of activities, which may inform intervention design.

Case-cohort study of plasma phospholipid fatty acid profiles, cognitive function, and risk of dementia: a secondary analysis in the Ginkgo Evaluation of Memory Study

Phospholipids are biomarkers of dietary fat intake and metabolism, linked to several cardiometabolic disorders. Few prospective studies have assessed plasma phospholipids in relation to dementia risk and cognitive function. We aimed to evaluate the association between a decrease in linoleic acid accompanied with an increase in other fatty acids and cognitive function and dementia risk. We conducted a case-cohort study nested within the Ginkgo Evaluation of Memory Study. We included 1252 participants, 498 of whom who developed dementia during a mean of 5 y of follow-up. We measured 45 individual plasma phospholipids (as a percentage of total plasma phospholipid fatty acids) by GC and related these to Modified Mini-Mental State Examination (3MSE) scores at baseline and neurologist-adjudicated incidence of all-cause dementia and Alzheimer disease (AD), adjusting for sociodemographic and clinical characteristics. Substitution of 1% of SFAs for 1% of linoleic acid, the predominant polyunsaturated n-6 (ɷ-6) fatty acid, was associated with higher risk of dementia (HR per 1% of SFAs instead of linoleic acid=1.03; 95% CI: 1.00, 1.07) and a 0.08 point lower 3MSE score at baseline (95% CI: -0.12, -0.03), signifying worse cognitive function. When compared with linoleic acid, we found no associations of total monounsaturated, n-3 polyunsaturated, or trans fatty acids with risk of dementia or AD. However, the substitution of 1% of the marine n-3 PUFA DHA for linoleic acid was associated with lower risk of dementia (HR=0.86 per 1% of DHA instead of linoleic acid; 95% CI: 0.76, 0.96). These associations were not modified by apolipoprotein E genotype, mild cognitive impairment at baseline, age, or sex. Specific elements of diet may be associated with late-life dementia, a hypothesis that requires formal testing in randomized controlled trials and that represents a possible preventive intervention.

The Association between Gait Speed and Falls in Community Dwelling Older Adults with and without Mild Cognitive Impairment.

(1) Background: Falls are common in older adults and result in injuries, loss of independence, and death. Slow gait is associated with falls in older adults, but few studies have assessed the association between gait speed and falls among those with mild cognitive impairment (MCI). (2) Methods: The association between gait speed and falls was assessed in 2705 older adults with and without MCI participating in the Ginkgo Evaluation of Memory Study. Gait speed was measured via a 15-foot walk test and fall history through self-report. We used data collected at the 12-month (2001–2003) and 18-month visits (2002–2004). (3) Results: Participant average age was 78.5 years (sd = 3.2); 45% were female, and 14% had MCI at baseline. The average gait speed was 0.93 m/s (sd = 0.20). Sixteen percent (n = 433) and 18% (n = 498) reported at least one fall at the 12-month and 18-month visits, respectively. Faster gait speed was associated with decreased risk of falling (RR: 0.95, 95% CI: 0.91, 0.99) for every 10 cm/s increase in gait speed adjusted for age, gender, study arm, site, and MCI status. (4) Conclusions: The relationship between gait speed and risk of falling did not vary by MCI status (interaction p-value = 0.78).

Plasma antioxidants and risk of dementia in older adults.

IntroductionPlant‐based diets rich in fruits and vegetables have been associated with lower risk of dementia, but the specific role of antioxidants, a key class of bioactive phytochemicals, has not been well ascertained.MethodsWe measured antioxidants in a case‐cohort study nested within the Ginkgo Evaluation of Memory Study. We included 996 randomly selected participants and 521 participants who developed dementia, of which 351 were diagnosed with Alzheimer's disease (AD) during a median of 5.9 years of follow‐up. We measured baseline plasma levels of retinol, α‐, and γ‐tocopherol; zeaxanthin and lutein (combined); beta‐cryptoxanthin; cis‐lycopene; trans‐lycopene; α‐carotene; and trans‐β‐carotene by organic phase extraction followed by chromatographic analysis and related these to neurologist‐adjudicated risks of all‐cause dementia and AD.ResultsPlasma retinol, α‐, and γ‐tocopherol, and carotenoids were not significantly related to risk of dementia or AD. Associations were not significant upon Bonferroni correction for multiple testing and were consistent within strata of sex, age, apolipoprotein E ε4 genotype, mild cognitive impairment at baseline, and intake of multivitamin, vitamin A or β‐carotene, or vitamin E supplements. Higher trans‐β‐carotene tended to be related to a higher risk of dementia (adjusted hazard ratio [HR] per 1 standard deviation [SD] higher trans‐β‐carotene: 1.10; 95% confidence interval [CI]: 1.00, 1.20) and α‐carotene tended to be associated with higher risk of AD only (adjusted HR per 1 SD higher α‐carotene: 1.15; 95% CI: 1.02, 1.29).DiscussionPlasma antioxidants were not significantly associated with risk of dementia or AD among older adults. Similar studies in younger populations are required to better understand the association between plasma antioxidants and dementia risk.

Depressive symptoms and risk of dementia in non‐depressed older adults

AbstractBackgroundThe relationship between depression and dementia is complex. Whether depression serves as a risk factor, prodromal symptom, or comorbidity of dementia remains unclear. Longitudinal studies that establish temporality of these conditions in late life may shed light on their relationship.MethodWe analyzed data from the Ginkgo Evaluation of Memory Study (GEMS) initiated in 2000 and followed for 8 years to determine incident dementia and its subtypes Alzheimer’s disease (AD) and vascular dementia (VaD). Inclusion criteria for enrollment in GEMS required participants to have a Center for Epidemiology Studies Depression score (CES‐D) &lt;16 or to be on treatment for depression. Dementia was determined by consensus of study neurologists based on standardized criteria using neuropsychiatric testing, MRI imaging, and comorbidities. Cox Proportional Hazards Regression was used to evaluate the associations of dementia (n=515), AD (without VaD, n=348) and VaD (with or without AD, n=145) with number of depressive symptoms at baseline. We determined the optimum cutpoint for depressive symptoms to predict dementia using Receiver Operating Characteristic (ROC) curves. Adjustments for age, gender, race, education, area level income, and study site were included in models.Result3,042 participants mean age 78.6 (SD 3.3), 46% women, mean follow‐up time 5.5 (SD 1.6) person‐years, were included in analyses. Mean number of CES‐D depressive symptoms at baseline was 3.5 (SD 3.2) with 525 participants reporting none. Number of depressive symptoms was associated with an increased risk of dementia (HR:1.09, 95% CI:1.06‐1.12, p&lt;0.001), AD (HR:1.10, 95% CI:1.07‐1.13, p&lt;0.001) and VaD (HR:1.05, 95% CI:1.00‐1.10, p=0.04). The optimum cutpoint based on the ROC curve was 2.6 with sensitivity of 0.64 and specificity of 0.49. Participants who reported &gt; 3 depressive symptoms had a 45% increased risk of dementia compared to those with fewer symptoms (HR: 1.45, 95% CI:1.04‐2.04, p=0.03). Effect modification by presence of mild cognitive impairment (MCI) was found (p interaction = 0.008). Results were only significant for those without MCI.ConclusionReporting just a few depressive symptoms in late life may indicate future onset of dementia. These results suggest the need for close clinical follow‐up of cognitive impairment in these non‐depressed older adults.

Plasma phospholipid fatty acids, cognitive function, and risk of dementia among older adults

AbstractBackgroundPlasma phospholipids are biomarkers of dietary fat intake and metabolism which have been linked to several cardiometabolic disorders. Few prospective studies have assessed plasma phospholipids in relation to adjudicated dementia risk and cognitive decline.MethodWe measured plasma phospholipids in a case‐cohort study nested within the Ginkgo Evaluation of Memory Study. We included 911 randomly selected participants and 498 participants who developed dementia during a mean [SD] of 5.0 [1.8] years of follow‐up. We measured individual plasma phospholipids (as a percentage of total plasma phospholipid fatty acids) by gas chromatography with flame ionization detection. These were evaluated in association with the Modified Mini‐Mental State Examination (3MSE) scores at baseline and neurologist‐adjudicated risks of all‐cause dementia and Alzheimer’s disease (AD), adjusting for sociodemographic and clinical characteristics.ResultWhen compared with saturated fatty acids (SFA), we found no associations of total mono‐unsaturated (MUFA), polyunsaturated (PUFA), or trans‐fatty acids (TFA) with risk of dementia or AD. However, higher docosahexaenoic acid was associated with a lower risk of dementia (hazard ratio 0.80 per 1% of docosahexaenoic acid instead of SFA; 95% confidence interval: 0.71‐0.91). Similarly, higher PUFA was associated with 0.04 point higher 3MSE score at baseline (per 1% PUFA instead of SFA; 95% confidence interval: 0.01, 0.08) signifying better cognitive function.ConclusionsAlthough we did not find strong associations of mono‐unsaturated or TFA with risk of dementia or AD when compared with SFA, replacement with PUFA was associated with better baseline cognitive function, and replacement with the marine n‐3 fatty acid docosahexaenoic acid was associated with lower risk of dementia. This prospective study highlights the potential of dietary improvement to prevent dementia.

Evaluating commercially generated residential address histories in an aging population: the Ginkgo Evaluation of Memory Study

Background: Epidemiological studies of spatially varying exposures benefit from accurate long-term comprehensive residential address histories of study participants in order to accurately link locations to spatially and temporally resolved exposure information. Commercially available residential address history databases might help researchers establish historical address data retrospective to study onset. The Ginkgo Evaluation of Memory Study (GEMS) was a randomized trial in four US sites (Hagerstown MD, Pittsburgh PA, Sacramento CA, and Winston-Salem NC) from 2000-2008. We aimed to assess the accuracy and historical reach of LexisNexis residential histories for the 3,069 GEMS participants from 1980 to 2008. Methods: We submitted to LexisNexis a list of 3069 participant names and 4050 known addresses and dates of residency from 2000-2008. The query returned 10,966 addresses. We developed a set of specific rules along with a fuzzy matching algorithm, to establish a sequence of probable residential histories. The average length of histories per participant were then evaluated and compared across gender, study site, and age. Results: Almost all (97.8%) GEMS participants had at least a partial address history returned by LexisNexis for years prior to 2000. The earliest historical addresses had a median year of 1983 and 35.2% of participants had their earliest historical address going back to at least 1980. The biggest differences in average historical lengths were between study sites. Participants from Hagerstown had an average of between 2.9 and 6.0 fewer years of residential history than the other three sites. Additionally, males had between .56 and 1.23 more years on average than females. Conclusions: Commercial residential address systems have the potential to enhance health studies that require historical residential information. As these types of databases grow in accessibility and accuracy, historical databases can be a key tool of environmental epidemiologists. Demographics and geographic locations, however, could impact accuracy and address length.