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BACKGROUND: To examine the effect of intensive blood pressure control on the occurrence of subtypes of mild cognitive impairment (MCI) and determine the risk of progression to dementia or death. METHODS: Secondary analysis of a randomized trial of community-dwelling adults (≥50 years) with hypertension. Participants were randomized to a systolic blood pressure (SBP) goal of

Background: Identification of factors that may help to preserve cognitive function in late life could elucidate mechanisms and facilitate interventions to improve the lives of millions of people. However, the large number of potential factors associated with cognitive function poses an analytical challenge. Objective: We used data from the longitudinal Women’s Health Initiative Memory Study (WHIMS) and machine learning to investigate 50 demographic, biomedical, behavioral, social, and psychological predictors of preserved cognitive function in later life. Methods: Participants in WHIMS and two consecutive follow up studies who were at least 80 years old and had at least one cognitive assessment following their 80th birthday were classified as cognitively preserved. Preserved cognitive function was defined as having a score ≥39 on the most recent administration of the modified Telephone Interview for Cognitive Status (TICSm) and a mean score across all assessments ≥39. Cognitively impaired participants were those adjudicated by experts to have probable dementia or at least two adjudications of mild cognitive impairment within the 14 years of follow-up and a last TICSm score

OBJECTIVE Patients with type 2 diabetes are encouraged to lose weight, but excessive weight loss in older adults may be a marker of poor health and subsequent mortality. We examined weight change during the postintervention period of Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) with diabetes support and education (DSE) (control) in overweight/obese individuals with type 2 diabetes and sought to identify predictors of excessive postintervention weight loss and its association with mortality. RESEARCH DESIGN AND METHODS These secondary analyses compared postintervention weight change (year 8 to final visit; median 16 years) in ILI and DSE in 3,999 Look AHEAD participants. Using empirically derived trajectory categories, we compared four subgroups: weight gainers (n = 307), weight stable (n = 1,561), steady losers (n = 1,731), and steep losers (n = 380), on postintervention mortality, demographic variables, and health status at randomization and year 8. RESULTS Postintervention weight change averaged −3.7 ± 9.5%, with greater weight loss in the DSE than the ILI group. The steep weight loss trajectory subgroup lost on average 17.7 ± 6.6%; 30% of steep losers died during postintervention follow-up versus 10–18% in other trajectories (P < 0001). The following variables distinguished steep losers from weight stable: baseline, older, longer diabetes duration, higher BMI, and greater multimorbidity; intervention, randomization to control group and less weight loss in years 1–8; and year 8, higher prevalence of frailty, multimorbidity, and depressive symptoms and lower use of weight control strategies. CONCLUSIONS Steep weight loss postintervention was associated with increased risk of mortality. Older individuals with longer duration of diabetes and multimorbidity should be monitored for excessive unintentional weight loss.

RATIONALE AND OBJECTIVE: The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in those with and without CKD. STUDY DESIGN: Neuroimaging substudy of a randomized trial. SETTING & PARTICIPANTS: A subset of participants in the Systolic Blood Pressure Intervention Trial who underwent brain MRI studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). INTERVENTION: Participants were randomly assigned to intensive (systolic BP 30 mg/g (N=151), the effects of intensive versus standard BP treatment on change in global cerebral blood flow, WMLs and total brain volume were 1.91 ml/100g/min (95% CI −3.01, 6.82), 0.003 cm(3) (asinh transformed, 95% CI −0.13, 0.13), and −7.0 cm(3) (95% CI −13.3, −0.3), respectively. The overall treatment effects on cerebral blood flow and total brain volume were not modified by baseline eGFR or UACR; however the effect on WMLs was attenuated in participants with albuminuria (interaction p-value 0.04). LIMITATIONS: Measurement variability due to multi-site design. CONCLUSIONS: Among hypertensive adults with primarily early kidney disease, intensive versus standard blood pressure treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive blood pressure treatment targets on brain health in persons with early kidney disease. FUNDING: The Systolic Blood Pressure Intervention Trial was funded by the National Institutes of Health (including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke), and this substudy was funded by the National Institutes of Diabetes and Digestive and Kidney Diseases. TRIAL REGISTRATION: SPRINT was registered at ClinicalTrials.gov with the study number NCT01206062.

ImportanceThe Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive blood pressure control reduced cardiovascular morbidity and mortality. However, the legacy effect of intensive treatment is unknown.ObjectiveTo evaluate the long-term effects of randomization to intensive treatment with the incidence of cardiovascular and all-cause mortality approximately 4.5 years after the trial ended.Design, Setting, and ParticipantsIn this secondary analysis of a multicenter randomized clinical trial, randomization began on November 8, 2010, the trial intervention ended on August 20, 2015, and trial close-out visits occurred through July 2016. Patients 50 years and older with hypertension and increased cardiovascular risk but without diabetes or history of stroke were included from 102 clinic sites in the US and Puerto Rico. Analyses were conducted between October 2021 and February 2022.InterventionsRandomization to systolic blood pressure (SBP) goal of less than 120 mm Hg (intensive treatment group; n = 4678) vs less than 140 mm Hg (standard treatment group; n = 4683).Main Outcomes and MeasuresExtended observational follow-up for mortality via the US National Death Index from 2016 through 2020. In a subset of 2944 trial participants, outpatient SBP from electronic health records during and after the trial were examined.ResultsAmong 9361 randomized participants, the mean (SD) age was 67.9 (9.4) years, and 3332 (35.6%) were women. Over a median (IQR) intervention period of 3.3 (2.9-3.9) years, intensive treatment was beneficial for both cardiovascular mortality (hazard ratio [HR], 0.66; 95% CI, 0.49-0.89) and all-cause mortality (HR, 0.83; 95% CI, 0.68-1.01). However, at the median (IQR) total follow-up of 8.8 (8.3-9.3) years, there was no longer evidence of benefit for cardiovascular mortality (HR, 1.02; 95% CI, 0.84-1.24) or all-cause mortality (HR, 1.08; 95% CI, 0.94-1.23). In a subgroup of participants, the estimated mean outpatient SBP among participants randomized to intensive treatment increased from 132.8 mm Hg (95% CI, 132.0-133.7) at 5 years to 140.4 mm Hg (95% CI, 137.8-143.0) at 10 years following randomization.Conclusions and RelevanceThe beneficial effect of intensive treatment on cardiovascular and all-cause mortality did not persist after the trial. Given increasing outpatient SBP levels in participants randomized to intensive treatment following the trial, these results highlight the importance of consistent long-term management of hypertension.Trial RegistrationClinicalTrials.gov Identifier: NCT01206062

Background Epigenetic age acceleration (AgeAccel), which indicates faster biological aging relative to chronological age, has been associated with lower cognitive function. However, the association of AgeAccel with mild cognitive impairment (MCI) or dementia is not well-understood. We examined associations of 4 AgeAccel measures with incident MCI and dementia. Methods This prospective analysis included 578 older women from the Women’s Health Initiative Memory Study selected for a case–cohort study of coronary heart disease (CHD). Women were free of CHD and cognitive impairment at baseline. Associations of AgeAccel measures (intrinsic AgeAccel [IEAA], extrinsic AgeAccel [EEAA], AgeAccelPheno, and AgeAccelGrim) with risks for incident adjudicated diagnoses of MCI and dementia overall and stratified by incident CHD status were evaluated. Results IEAA was not significantly associated with MCI (HR, 1.23; 95% CI, 0.99–1.53), dementia (HR, 1.10; 95% CI, 0.88–1.38), or cognitive impairment (HR, 1.18; 95% CI, 0.99–1.40). In stratified analysis by incident CHD status, there was a 39% (HR, 1.39; 95% CI, 1.07–1.81) significantly higher risk of MCI for every 5-year increase in IEAA among women who developed CHD during follow-up. Other AgeAccel measures were not significantly associated with MCI or dementia. Conclusions IEAA was not significantly associated with cognitive impairment overall but was associated with impairment among women who developed CHD. Larger studies designed to examine associations of AgeAccel with cognitive impairment are needed, including exploration of whether associations are stronger in the setting of underlying vascular pathologies.

Few studies have examined associations between neighborhood built environments (BE) and longitudinally measured cognition. We examined whether four BE characteristics were associated with six-year change in global cognition and processing speed. We obtained data on 1816 participants without dementia from the Multi-Ethnic Study of Atherosclerosis. BE measures included social destination density, walking destination density, proportion of land dedicated to retail, and network ratio (street connectivity). Global cognition was measured with the Cognitive Abilities Screening Instrument (CASI) and processing speed with the Digit Symbol Coding test (DSC). Multivariable random intercept logistic models tested associations between neighborhood BE at 2010–2012 and maintained/improved cognition (versus decline) from 2010–2018, and mediation by minutes of physical activity (PA)/week. The sample was an average of 67 years old (standard deviation = 8.2) (first cognitive measurement) and racially/ethnically diverse (29% African American, 11% Chinese, 17% Hispanic, 44% White). Compared to individuals with no walking destinations in the 1-mile surrounding their residence, those with 716 walking destinations (maximum observed) were 1.24 times more likely to have maintain/improved DSC score (Odds ratio: 1.24, 95% confidence interval: 1.03–1.45). No other associations were observed between BE and cognition, and PA minutes/week did not mediate the association between walking destination density and DSC change. This study provides limited evidence for an association between greater neighborhood walking destinations and maintained/improved processing speed in older age and no evidence for associations between the other BE characteristics and cognition. Future studies with finer grained BE and cognitive measures and longer-term follow up may be required.

Introduction Little is known about how antecedent vascular risk factor (VRF) profiles impact late-life brain health. Methods We examined baseline VRFs, and cognitive testing and neuroimaging measures (β-amyloid [Aβ] PET, MRI) in a diverse longitudinal cohort (N = 159; 50% African-American, 50% White) from Wake Forest's Multi-Ethnic Study of Atherosclerosis Core. Results African-Americans exhibited greater baseline Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham stroke risk profile (FSRP), and atherosclerotic cardiovascular disease risk estimate (ASCVD) scores than Whites. We observed no significant racial differences in Aβ positivity, cortical thickness, or white matter hyperintensity (WMH) volume. Higher baseline VRF scores were associated with lower cortical thickness and greater WMH volume, and FSRP and CAIDE were associated with Aβ. Aβ was cross-sectionally associated with cognition, and all imaging biomarkers were associated with greater 6-year cognitive decline. Discussion Results suggest the convergence of multiple vascular and Alzheimer's processes underlying neurodegeneration and cognitive decline.

Background Hearing loss (HL) and menopausal hormone therapy (conjugated equine estrogens [CEE] and/or medroxyprogesterone acetate [MPA]) are separately associated with cognitive decline and increased risk of incident cognitive impairment. Joint effects of HL and HT could be associated with additive or synergistic decline in global cognition and risk of incident cognitive impairment among postmenopausal women. Methods Using the Women’s Health Initiative (WHI) Memory Study, 7,220 postmenopausal women with measures of HL, global cognition (Modified Mini-Mental State Examination score), and cognitive impairment (centrally adjudicated diagnoses of mild cognitive impairment and dementia) from 1996 to 2009. Multivariable linear mixed-effects models were used to analyze rate of change in global cognition. Accelerated failure time models were used to evaluate time to incident cognitive impairment, stratified by HT. Results Within the CEE-Alone trial, observed adverse effects of CEE-Alone on change in global cognition did not differ by HL, and estimated joint effects of HL and CEE-Alone were not associated with incident cognitive impairment. Within the CEE+MPA trial, while HL did not independently accelerate time to cognitive impairment, the adverse effect of CEE+MPA on global cognition was heightened in older women with HL. Older women on CEE+MPA either with HL (time ratio [TR] = 0.82, 95% confidence interval [CI]: 0.71, 0.94) or with normal hearing (TR = 0.86, 95% CI: 0.76, 0.97) had faster time to cognitive impairment than those with normal hearing and placebo. Conclusions HL may accentuate the adverse effect of CEE+MPA, not CEE-Alone, on global cognitive decline, not incident cognitive impairment, among postmenopausal women on HT.

Introduction Both high or low plasma amyloid levels have been associated with risk of dementia in nondemented subjects. Methods We examined baseline plasma β-amyloid (Aβ) levels in relationship to incident dementia during a period of 8.5 years in 2840 subjects age >75 years; 2381 were cognitively normal (CN) and 450 mild cognitive impairment. Results Increased plasma Aβ1-40 and Aβ1-42 levels were associated with gender (women), age, low education, creatinine levels, history of stroke, and hypertension. CN participants who developed dementia had lower levels of Aβ1-42 and Aβ1-42/Aβ1-40 ratio compared with those who did not. Aβ levels did not predict dementia in mild cognitive impairment participants. Discussion There was an inverse association between Aβ1-42 and Aβ1-42/Aβ1-40 ratio to risk of dementia in CN participants. Cerebral and cardiovascular disease and renal function are important determinants of increased Aβ levels and must be considered in evaluations of relationship of plasma Aβ and subsequent risk of dementia.

Objective While a number of single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) or cognitive impairment have been identified, independent replications remain the only way to validate proposed signals. We investigated SNPs in candidate genes associated with either cognitive impairment or AD pathogenesis and their relationships with probable dementia (PD) in the Women's Health Initiative Memory Study (WHIMS). Methods We analyzed 96 SNPs across five genes (APOE/TOMM40, BDNF, COMT, SORL1, and KIBRA) in 2857 women (ages ≥65) from the WHIMS randomized trials of hormone therapy using a custom Illumina GoldenGate assay; 19% of the sample were MCI (N = 165) or PD (N = 387), and the remaining 81% were free of cognitive impairment. SNP associations were evaluated for PD in non-Hispanic whites adjusting for age and HT using logistic regression under an additive genetic model. Results One SNP (rs157582), located in the TOMM40 gene nearby APOE, was associated with the PD phenotype based on a P value accounting for multiple comparisons. An additional 12 SNPs were associated with the PD phenotype at P ≤ 0.05 (APOE: rs405509, rs439401; TOMM40: rs8106922, and KIBRA: rs4320284, rs11740112, rs10040267, rs13171394, rs6555802, rs2241368, rs244904, rs6555805, and rs10475878). Results of the sensitivity analyes excluding MCI were similar, with addition of COMT rs737865 and BDNF rs1491850 (P ≤ 0.05). Conclusions Our results in older women provide supporting evidence that the APOE/TOMM40 genes confer dementia risk and extend these findings to COMT, BDNF, and KIBRA. Our findings may lead to a better understanding of the role these genes play in cognition and cognitive impairment.

Objective To examine the association of global cognitive function assessed via the Montreal Cognitive Assessment (MoCA) and deficiencies in instrumental activities of daily living (IADL) on the Functional Activity Questionnaire (FAQ) in hypertensive older adults in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods In cross-sectional analysis, 9,296 SPRINT participants completed the MoCA at baseline. The FAQ was obtained from 2,705 informants for SPRINT participants scoring Results Participants who triggered FAQ administration were older, less educated, and more likely to be Black or Hispanic (p < 0.001). Sixty-one percent (n = 1,661) of participants’ informants reported no functional difficulties in IADLs. An informant report, however, of any difficulty on the FAQ was associated with lower MoCA scores after controlling for age, sex, race/ethnicity, and education (p < 0.05). Partial proportional odds regression indicates that participants scoring lower on the MoCA (in the 10th to Conclusions While lower global cognitive function was strongly associated with IADL deficits on FAQ, informants indicated no functional difficulties for the majority of SPRINT participants, despite low MoCA scores. These findings can help with designing future studies which aim to detect mild cognitive impairment and/or dementia in large, community-dwelling populations.

Introduction: Weight loss and increased physical activity interventions are commonly recommended for individuals with type 2 diabetes (T2D) and overweight or obesity. We examined the impact of randomization to an intensive lifestyle intervention (ILI) on trajectories of cognitive function over 10 years in a cohort of participants in a randomized clinical trial who had T2D and overweight/obesity at baseline. Methods: Participants aged 45–76 years were enrolled in 2001–2004 and were randomized to the ILI or a diabetes support and education (DSE) condition. Cognitive function was assessed in 3,938 participants at up to 4 time points 8–18 years after randomization. General linear mixed effects models examined cognitive trajectories over time. Subgroup analyses focused on sex, individuals with baseline body mass index >30, those carrying the APOE ε4 allele, and those with a baseline history of cardiovascular disease (CVD). Results: Overall, there were no differences in the rate of cognitive decline by intervention arm. Subgroup analyses showed that participants who had a baseline history of CVD and were randomized to the ILI arm of the study performed significantly worse on the Stroop Color Word Test than those in the DSE arm. Discussion/Conclusions: The ILI did not result in preserved cognitive function or slower rates of cognitive decline in this cohort of individuals who had T2D and were overweight or obese at baseline.

Background Increasing evidence shows that cognition and gait speed are associated and are important measures of health among older adults. However, previous studies have used different methods to assess these 2 outcomes and lack sufficient sample size to examine heterogeneity among subgroups. This study examined how the relationship between global cognitive function and gait speed are influenced by age, gender, and race utilizing an integrated data analysis approach. Method Data on cognition (Montreal Cognitive Assessment [MoCA], Mini-Mental Status Examination [MMSE], and Modified Mini-Mental State Examination [3MSE]) and gait speed (range: 4–400 m) were acquired and harmonized from 25 research studies (n = 2802) of adults aged 50+ from the Wake Forest Older American Independence Center. Multilevel regression models examined the relationship between predicted values of global cognitive function (MoCA) and gait speed (4-m walk), including heterogeneity by age, race, and gender. Results Global cognitive function and gait speed exhibited a consistent positive relationship among whites with increasing age, while this was less consistent for African Americans. That is, there was a low correlation between global cognitive function and gait speed among African Americans aged 50–59, a positive correlation in their 60s and 70s, then a negative correlation thereafter. Conclusion Global cognition and gait speed exhibited a curvilinear U-shaped relationship among whites; however, the association becomes inverse in African Americans. More research is needed to understand this racial divergence and could aid in identifying interventions to maintain cognitive and gait abilities across subgroups.

Evidence on the relations between heart rate, brain morphology, and cognition is limited. We examined the associations of resting heart rate (RHR), visit-to-visit heart rate variation (VVHRV), brain volumes and cognitive impairment. The study sample consisted of postmenopausal women enrolled in the Women's Health Initiative Memory Study and its ancillary MRI sub-studies (WHIMS-MRI 1 and WHIMS-MRI 2) without a history of cardiovascular disease, including 493 with one and 299 women with 2 brain magnetic resonance imaging (MRI) scans. HR readings were acquired annually starting from baseline visit (1996-1998). RHR was calculated as the mean and VVHRV as standard deviation of all available HR readings. Brain MRI scans were performed between 2005 and 2006 (WHIMS-MRI 1), and approximately 5 years later (WHIMS-MRI 2). Cognitive impairment was defined as incident mild cognitive impairment or probable dementia until December 30, 2017. An elevated RHR was associated with greater brain lesion volumes at the first MRI exam (7.86 cm3 [6.48, 9.24] vs 4.78 cm3 [3.39, 6.17], p-value0.0001) and with significant increases in lesion volumes between brain MRI exams (6.20 cm3 [4.81, 7.59] vs 4.28 cm3 [2.84, 5.73], p-value = 0.0168). Larger ischemic lesion volumes were associated with a higher risk for cognitive impairment (Hazard Ratio [95% confidence interval], 2.02 [1.18, 3.47], p-value = 0.0109). Neither RHR nor VVHRV were related to cognitive impairment. In sensitivity analyses, we additionally included women with a history of cardiovascular disease to the study sample. The main results were consistent to those without a history of cardiovascular disease. In conclusion, these findings show an association between elevated RHR and ischemic brain lesions, probably due to underlying subclinical disease processes.

Background: Diabetes is a well-known risk factor for dementia. Despite emerging evidence that higher glucose variability is associated with cognitive decline and hypoglycemia is associated with increased risk for dementia, few studies have investigated the relationship of lower fasting glucose and glucose variability with cognitive performance in the general population. Hypothesis: Diabetic and lower levels of fasting glucose and higher visit-to-visit glucose variability over 10 years are associated with worse cognitive performance. Methods: Participants in the Multi-Ethnic Study of Atherosclerosis (N = 4,591; mean age 69.7 ± 9.4 years) completed a cognitive assessment at Exam 5 including the Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS, Forward and Backward combined) tests measuring global cognitive performance, executive function/processing speed, and working memory, respectively. We defined fasting glucose categories as low (β [95% confidence limits]) from regression models adjusted for age, sex, race/ethnicity, education, income, cardiovascular risk factors, and APOE genotype. Results: Relative to normal glucose, participants with diabetic fasting glucose performed significantly worse on the CASI (Exam 1 β = -0.75 [-1.36, -0.15]; Exam 5 β = -0.30 [-0.83, 0.23]), DSC (Exam 1 β = -2.97 [-4.20, -1.74]; Exam 5 β = -1.26 [-2.34, -0.18]), and DS (Exam 1 β = -0.39 [-0.72, -0.07]; Exam 5 β = -0.29 [-0.58, -0.003]). In contrast, participants with low Exam 1 fasting glucose performed significantly better on the DSC (Exam 1 β = 1.55 [0.45, 2.65]) and similarly on the CASI and DS compared to those with normal fasting glucose. Adjusting for glucose lowering medication attenuated associations with the DSC and DS but not the CASI. Accounting for heterogeneity in the low glucose category by hypoglycemia (β = -0.36 [-0.60, -0.12]) and DSC ( β = -1.14 [-1.63, -0.65]). Associations were consistent across race and sex. Conclusions: Results support the hypothesis that hyperglycemia and higher glucose variability are associated with worse cognitive performance. Despite previous suggestion of a link between hypoglycemia and incident dementia, lower antecedent fasting glucose may be associated with better executive function/processing speed in this population-based sample.

Before 2002, hormone therapy (HT) was commonly prescribed to restore naturally diminishing hormonal levels during and after menopause. HT was also thought to prevent many health conditions faced by menopausal women, including osteoporosis, heart disease, cancer, and dementia. Support for these claims came primarily from epidemiological studies and basic research suggesting biological plausibility. Women now live a third of their life beyond ovarian function cessation. Given that cognitive impairment and dementia increase with age, increasing life expectancy may result in greater public health consequences. This chapter reviews the potential risks and benefits of HT, with a focus on cognitive function. It also discusses the implications of menopausal HT on cognitive impairment and dementia prevention, diagnosis, and treatment for aging women.

BACKGROUND: Intensively treating hypertension may benefit cardiovascular disease and cognitive function, but at the short-term expense of reduced kidney function. METHODS: We investigated markers of kidney function and the effect of intensive hypertension treatment on incidence of dementia and mild cognitive impairment (MCI) in 9361 participants in the randomized Systolic Blood Pressure Intervention Trial, which compared intensive versus standard systolic BP lowering (targeting

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INTRODUCTION: There is no accepted classification of cognitive impairment in cancer survivors. We assess the extent of mild cognitive impairment (MCI) syndrome in brain tumor survivors using criteria adapted from the National Institute on Aging and the Alzheimer’s Association (NIA-AA). METHODS: We retrospectively reviewed the cognitive data of brain tumor survivors post-radiation therapy (RT) enrolled from 2008 to 2011 in a randomized trial of donepezil versus placebo for cognitive impairment. One hundred and ninety eight adult survivors with primary or metastatic brain tumors who were ≥ 6 months post RT were recruited at 24 sites in the United States. Cognitive function was assessed at baseline, 12 and 24 weeks post-randomization. For this analysis, we used baseline data to identify MCI and possible dementia using adapted NIA-AA criteria. Cases were subtyped into four groups: amnestic MCI-single domain (aMCI-sd), amnestic MCI-multiple domain (aMCI-md), non-amnestic MCI-single domain (naMCI-sd), and non-amnestic MCI-multiple domain (naMCI-md). RESULTS: One hundred and thirty one of 197 evaluable patients (66%) met criteria for MCI. Of these, 13% were classified as aMCI-sd, 58% as aMCI-md, 19% as naMCI-sd, and 10% as naMCI-md. Patients with poorer performance status, less education, lower household income and those not working outside the home were more likely to be classified as MCI. CONCLUSION: Two-thirds of post-RT brain tumor survivors met NIA-AA criteria for MCI. This taxonomy may be useful when applied to brain tumor survivors because it defines cognitive phenotypes that may be differentially associated with course, treatment response, and risk factor profiles.

Author(s): Espeland, Mark A; Chen, Jiu-Chiuan; Weitlauf, Julie; Hayden, Kathleen M; Rapp, Stephen R; Resnick, Susan M; Garcia, Lorena; Cannell, Brad; Baker, Laura D; Sachs, Bonnie C; Tindle, Hilary A; Wallace, Robert; Casanova, Ramon; Women's Health Initiative Memory Study Magnetic Resonance Imaging Study Group | Abstract: ObjectivesTo examine whether trajectories of global cognitive function over time in studies that change assessment protocols may be modeled based on an individual's performance relative to others in the study cohort.DesignExtended follow-up of a cohort originally enrolled in a clinical trial of postmenopausal hormone therapy.SettingThe Women's Health Initiative Memory Study switched from an in-person interview with the Modified Mini-Mental State Examination to a telephone-based interview with the modified Telephone Interview for Cognitive Status to assess global cognitive function over long-term follow-up.ParticipantsWomen aged 75 to 92 (N=2,561).MeasurementsAnnual cognitive assessments from participants, ranked according to age-, race- and ethnicity-adjusted performance levels, were used to identify distinct trajectories. Participants assigned to the resulting trajectories were compared for selected risk factor profiles.ResultsOur approach grouped participants into five trajectories according to relative cognitive performance over time. These groups differed significantly according to 3 known risk factors for cognitive decline-education level, apolipoprotein E-ϵ4 genotype, and type 2 diabetes mellitus-and a biomarker based on brain structure that has been linked to cognitive decline and Alzheimer's disease. Participants with consistently low relative levels of cognitive function over time and those whose relative performance over time declined to these levels tended to have poorer risk factor profiles.ConclusionLongitudinal measures of an individual's relative performance on different assessment protocols for global cognitive function can be used to identify trajectories of change over time that appear to have internal validity with respect to known risk factors.

Background Lifestyle interventions to reduce weight and increase activity may preserve higher-order cognitive abilities in overweight/obese adults with type 2 diabetes (T2D). Methods Adults (N = 5,084) with T2D who enrolled in a randomized clinical trial of a 10-year intensive lifestyle intervention (ILI) compared with diabetes support and education were queried at baseline and repeatedly during follow-up for complaints about difficulties in memory, problem-solving, and decision-making abilities. Results For those without baseline complaints, assignment to ILI was associated with lower odds that complaints would emerge during follow-up for decision-making ability (odds ratio [OR]=0.851, [95% CI, 0.748,0.967], p=0.014), and, among individuals who were not obese, lower odds that complaints would emerge about problem-solving ability (OR=0.694 [0.510,0.946]). No cognitive benefits from ILI were seen for individuals with baseline complaints about cognitive abilities. ILI may have exacerbated the severity of complaints about problem-solving ability during follow-up among individuals with baseline complaints and cardiovascular disease (OR=2.949 [1.378,6.311]). Conclusions A long-term multidomain ILI may reduce the likelihood that complaints about difficulties in higher-order cognitive abilities will emerge in T2D adults without pre-existing complaints. Among those with pre-existing complaints, the ILI did not prevent increases in complaint severity.

Mara Z Vitolins,1 L Douglas Case,1 Stephen R Rapp,2 Mark O Lively,3 Edward G Shaw,4 Michelle J Naughton,5 Jeffrey Giguere,6 Glenn J Lesser7 1Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Psychiatry and Behavioral Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 5Department of Internal Medicine, The Ohio State University, Columbus, OH, USA; 6Greenville Community Oncology Research Program of the Carolinas, Greenville, SC, USA; 7Department of Internal Medicine-Hematology and Oncology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA Purpose: Women with breast cancer were randomized to receive coenzyme Q10 (CoQ10) plus Vitamin E or placebo in a clinical trial. The objective of this evaluation is to examine the association between participant self-reported adherence to the study supplements and changes in plasma biomarker levels.Patients and methods: Correlation coefficients quantified the association between changes in alpha-tocopherol and CoQ10 levels and the association between self-reported adherence and changes in biomarkers. Participants were categorized by self-reported adherence; Kruskal–Wallis tests compared changes in alpha-tocopherol and CoQ10 levels between self-reported adherence groups.Results: Women (N=155) provided baseline and post-treatment biomarkers; 147 completed at least one diary. While changes in alpha-tocopherol and CoQ10 levels were moderately correlated, correlations ranged from 0.40 to 0.48, association between self-reported adherence and plasma alpha-tocopherol or CoQ10 levels was weak; correlations ranged from 0.10 to 0.29 at weeks 8, 16, and 24. Some participants with high self-reported adherence actually had decreases in their biomarker levels.Conclusion: These findings support that self-reported adherence is likely to be overestimated. Biological and other measures of adherence that can better identify true adherence to study pills provided in clinical trials are greatly needed as they may assist in improving the interpretation of findings of future clinical trials. Keywords: adherence, self-report, blood biomarkers, clinical trial, CoQ10, alpha-tocopherol

Introduction Aim is to evaluate validity, reliability, diagnostic precision, and user acceptability of computer simulations of cognitively demanding tasks when administered to older adults with and without cognitive impairment. Methods Five simulation modules were administered to 161 individuals aged ≥60 years with no cognitive impairment (N = 81), mild cognitive impairment (N = 52), or dementia (N = 28). Groups were compared on total accuracy and time to complete the tasks (seconds). Receiver operating characteristics were evaluated. Reliability was assessed over one month. Participants rated face validity and acceptability. Results Total accuracy (P

Studies on the relationship of cholesterol concentrations and lipid-lowering medications with dementia risk have yielded inconsistent findings. Therefore, we investigated the association of lipid concentrations and lipid-lowering medications with cognitive function in the Multi-Ethnic Study of Atherosclerosis across 3 different cognitive domains assessed by means of the Cognitive Abilities Screening Instrument (CASI; version 2), the Digit Symbol Coding (DSC) Test, and the Digit Span (DS) Test in 2010-2012. After adjustment for sociodemographic and confounding factors, including concentrations of other lipids and use of lipid-lowering medication, higher total cholesterol, low-density lipoprotein cholesterol, and non-high-density-lipoprotein cholesterol concentrations were modestly associated with higher DS Test scores. None of the lipid parameters were associated with CASI or DSC Test scores. Similarly, changes in lipid concentrations were not associated with any cognitive function test score. Using treatment effects model analysis and after adjusting for confounding factors, including lipid concentrations, the use of any lipid-lowering medication, especially statins, was associated with higher scores on the CASI and backward DS tests but not on the DSC and forward DS tests. Our study does not support a robust association between lipid concentrations and cognitive function or between the use of lipid-lowering medication, especially statins, and worse cognitive function.

Introduction This study sought to determine whether 10 years of assignment to intensive lifestyle intervention (ILI) relative to diabetes support and education leads to better cognition. We examine intervention effects overall and among clinical subgroups, and report correlations between computer‐administered and interviewer‐administered cognitive batteries. Methods The Action for Health in Diabetes (Look AHEAD) was a 16‐site randomized controlled trial with overweight/obese individuals (aged 45–76) who had type 2 diabetes. The NIH Toolbox Cognition Battery tests developed to measure cognition across the lifespan were used to evaluate cognition. Results were compared with standard paper‐and‐pencil tests. The Toolbox and paper‐and‐pencil tests were administered an average of 10.9 years after randomization to 1002 participants. Results Toolbox measures significantly correlated with interviewer‐administered measures, with the strongest correlations between the Toolbox Fluid Cognition Composite and Trails B (r = −0.64, P .05 for all). Subgroup analyses identified different intervention effects within baseline body mass index groups for Picture Sequence Memory (P = .01), within baseline cardiovascular disease groups for Picture Vocabulary (P = .01) and Fluid Cognition Composite (P = .02) measures, and within baseline age groups for Picture Vocabulary (P = .02). Discussion Correlations between Toolbox and interviewer‐administered outcomes provide a measure of internal validity. Findings suggest no overall effect of the intervention on cognition and that an ILI resulting in weight loss may have negative implications for cognition in individuals aged ≥60, with previous history of cardiovascular disease, and those with body mass index ≥40.

Background Positive affect (PA) and negative affect (NA) reflect subjective emotional experiences. Although related to depression and anxiety, these dimensions are distinct constructs representing affective states and patterns. Prior studies suggest that elevated depressive symptoms are associated with risk of mild cognitive impairment (MCI) and probable dementia, but whether affective states are associated with cognitive impairment is still unknown. The present study examined relationships between baseline affective states and cognitive impairment (MCI, probable dementia) in nondepressed women. Method Baseline PA and NA were assessed in postmenopausal women (N = 2,137; mean age = 73.8 years) from the Women's Health Initiative Study of Cognitive Aging (WHISCA) using the Positive and Negative Affect Schedule (PANAS). Women were followed annually for an average of 11.3 years; those with elevated depressive symptoms at baseline were excluded. Results Higher NA was associated with a higher risk of MCI and probable dementia, even after adjusting for important covariates including age, education, sociodemographic, lifestyle, and cardiovascular risk factors, global cognition, and hormone therapy assignment at baseline. PA was not significantly associated with either outcome. Conclusions We present the first evidence to date that greater NA, even in the absence of elevated depressive symptoms, is associated with higher risk of MCI and dementia. This suggests that NA may be an important, measureable and potentially modifiable risk factor for age-related cognitive decline.

BACKGROUND: Diabetes adversely impacts cognition. Lifestyle change can improve diabetes control and potentially improve cognition. We examined whether weight loss through reduced caloric intake and increased physical activity was associated with slower cognitive aging in older adults with type 2 diabetes mellitus. METHODS: The Look AHEAD randomized controlled clinical trial delivered 10 years of intensive lifestyle intervention (ILI) that yielded long-term weight losses. During 5 years spanning the end of intervention and postintervention follow-up, repeated cognitive assessments were obtained in 1,091 individuals who had been assigned to ILI or a control condition of diabetes support and education (DSE). We compared the means and slopes of scores on cognitive testing over these repeated assessments. RESULTS: Compared with DSE, assignment to ILI was associated with a −0.082 SD deficit in mean global cognitive function across repeated assessments (p = .010). However, overweight (body mass index [BMI] < 30 kg/m(2)) ILI participants had 0.099 (95% confidence interval [CI]: −0.006, 0.259) better mean global cognitive function compared with overweight DSE participants, while obese (BMI ≥ 30 kg/m(2)) ILI participants had −0.117 (−0.185, −0.049) SD worse mean composite cognitive function scores (interaction p = .014) compared to obese DSE participants. For both overweight and obese participants, cognitive decline was marginally (−0.014 SD/y overall) steeper for ILI participants (p = .068), with 95% CI for differences in slopes excluding 0 for measures of attention and memory. CONCLUSIONS: The behavioral weight loss intervention was associated with small relative deficits in cognitive function among individuals who were obese and marginally greater cognitive decline overall compared to control. ClinicalTrials.gov Identifier: NCT00017953

Introduction The Mediterranean and Dietary Approaches to Stop Hypertension diets have been associated with lower dementia risk. We evaluated dietary inflammatory potential in relation to mild cognitive impairment (MCI)/dementia risk. Methods Baseline food frequency questionnaires from n = 7085 women (aged 65–79 years) were used to calculate Dietary Inflammatory Index (DII) scores that were categorized into four groups. Cognitive function was evaluated annually, and MCI and all-cause dementia cases were adjudicated centrally. Mixed effect models evaluated cognitive decline on over time; Cox models evaluated the risk of MCI or dementia across DII groups. Results Over an average of 9.7 years, there were 1081 incident cases of cognitive impairment. Higher DII scores were associated with greater cognitive decline and earlier onset of cognitive impairment. Adjusted hazard ratios (HRs) comparing lower (anti-inflammatory; group 1 referent) DII scores to the higher scores were group 2-HR: 1.01 (0.86–1.20); group 3-HR: 0.99 (0.82–1.18); and group 4-HR: 1.27 (1.06–1.52). Conclusions Diets with the highest pro-inflammatory potential were associated with higher risk of MCI or dementia.

Background Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline. However, methodological limitations have limited the quality of this evidence. Heterogeneity in study design, cognitive test administration, and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice. We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes. Methods Tests of memory, visuo-spatial construction, language, psychomotor speed, and executive function were administered. Test scores were standardized to z-scores and averaged to yield domain scores. Linear random effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes. Results Among the 3,069 adults, aged 72-96 years, 9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with diabetes exhibited greater baseline differences in a test of executive function (trail making test, Part B) and greater declines in a test of language (phonemic verbal fluency). For the composite cognitive domain scores, participants with diabetes exhibited lower baseline executive function and global cognition domain scores, but no significant differences in the rate of decline. Conclusions Identifying cognitive domains most affected by diabetes can lead to targeted risk modification, possibly in the form of lifestyle interventions such as diet and physical activity, which we know to be beneficial for improving vascular risk factors, such as diabetes, and therefore may reduce the risk of executive dysfunction and possible dementia.

Objective The purpose of this study was to examine the relationship between dynapenia and metabolic risk factors in obese and nonobese older adults. Methods A total of 1453 men and women (age ≥70 years) from the Lifestyle Interventions and Independence for Elders (LIFE) Study were categorized as (1) nondynapenic/nonobese (NDYN-NO), (2) dynapenic/nonobese (DYN-NO), (3) nondynapenic/obese (NDYN-O), or (4) dynapenic/obese (DYN-O), based on muscle strength (Foundation for the National Institute of Health criteria) and body mass index. Dependent variables were blood lipids, fasting glucose, blood pressure, presence of at least 3 metabolic syndrome (MetS) criteria, and other chronic conditions. Results A significantly higher likelihood of having abdominal obesity criteria in NDYN-NO compared with DYN-NO groups (55.6 vs 45.1%, P ≤ .01) was observed. Waist circumference also was significantly higher in obese groups (DYN-O = 114.0 ± 12.9 and NDYN-O = 111.2 ± 13.1) than in nonobese (NDYN-NO = 93.1 ± 10.7 and DYN-NO = 92.2 ± 11.2, P ≤ .01); and higher in NDYN-O compared with DYN-O ( P = .008). Additionally, NDYN-O demonstrated higher diastolic blood pressure compared with DYN-O (70.9 ± 10.1 vs 67.7 ± 9.7, P ≤ .001). No significant differences were found across dynapenia and obesity status for all other metabolic components ( P > .05). The odds of having MetS or its individual components were similar in obese and nonobese, combined or not with dynapenia (nonsignificant odds ratio [95% confidence interval]). Conclusion Nonobese dynapenic older adults had fewer metabolic disease risk factors than nonobese and nondynapenic older adults. Moreover, among obese older adults, dynapenia was associated with lower risk of meeting MetS criteria for waist circumference and diastolic blood pressure. Additionally, the presence of dynapenia did not increase cardiometabolic disease risk in either obese or nonobese older adults.

Background We examined whether changes in metabolic factors over 10 years were associated with cognitive performance. Methods Participants from the Multi-Ethnic Study of Atherosclerosis were followed since baseline (2000–2002) with five clinical examinations. At exam 5 (2010–2012), they received a short cognitive battery (Cognitive Abilities Screening Instrument [CASI], Digit Symbol Coding [DSC], and Digit Span [DS]). We examined associations between baseline metabolic factors and their changes over time before cognitive testing. Results Among 4392 participants, baseline metabolic disorders (fasting glucose, systolic and diastolic blood pressures) were significantly associated with poorer CASI, DSC, and DS scores measured 10 years later. Increases in blood pressure were associated with lower cognitive performance. Results did not differ by race/ethnicity and were stronger among those without the APOE e4 allele. Conclusions Cognitive performance was associated with antecedent abnormalities in glucose metabolism and blood pressure increases. Findings appeared stronger among APOE e4-negative participants.

BACKGROUND: Hearing loss (HL) and menopausal hormone therapy (conjugated equine estrogens [CEE] and/or medroxyprogesterone acetate [MPA]) are separately associated with cognitive decline and increased risk of incident cognitive impairment. Joint effects of HL and HT could be associated with additive or synergistic decline in global cognition and risk of incident cognitive impairment among postmenopausal women. METHODS: Using the Women’s Health Initiative (WHI) Memory Study, 7,220 postmenopausal women with measures of HL, global cognition (Modified Mini-Mental State Examination score), and cognitive impairment (centrally adjudicated diagnoses of mild cognitive impairment and dementia) from 1996 to 2009. Multivariable linear mixed-effects models were used to analyze rate of change in global cognition. Accelerated failure time models were used to evaluate time to incident cognitive impairment, stratified by HT. RESULTS: Within the CEE-Alone trial, observed adverse effects of CEE-Alone on change in global cognition did not differ by HL, and estimated joint effects of HL and CEE-Alone were not associated with incident cognitive impairment. Within the CEE+MPA trial, while HL did not independently accelerate time to cognitive impairment, the adverse effect of CEE+MPA on global cognition was heightened in older women with HL. Older women on CEE+MPA either with HL (time ratio [TR] = 0.82, 95% confidence interval [CI]: 0.71, 0.94) or with normal hearing (TR = 0.86, 95% CI: 0.76, 0.97) had faster time to cognitive impairment than those with normal hearing and placebo. CONCLUSIONS: HL may accentuate the adverse effect of CEE+MPA, not CEE-Alone, on global cognitive decline, not incident cognitive impairment, among postmenopausal women on HT.

PurposeTo determine if a larger cup-to-disc ratiois associated with poor cognitive function in postmenopausal women without glaucoma or ocular hypertension.MethodsWe used data from the Women's Health Initiative (WHI) hormone trial, originally designed to test effects of hormone therapy (HT) on various health outcomes. Large cup-to-disc ratio was defined as greater than 0.6 in either eye based on stereoscopic optic nerve photographs. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) in the WHI Memory Study. Exclusions were no information on optic nerve grading; no 3MSE scores at the time of the eye examination, ocular hypertension (intraocular pressure >23mm Hg, Goldmann applanation tonometry), or glaucoma medication use. A generalized linear model for log-transformed 3MSE scores was used for determining the association between large cup-to-disc ratio and 3MSE scores, adjusting for age, race, diabetes, body mass index, cardiovascular disease, smoking, HT randomization, education, and diabetic retinopathy.ResultsAnalyses included 1636 women (mean age ± standard deviation, 69.57 ± 3.64 years; 90.39% white). Of those, 122 women had large cup-to-disc ratio. The mean 3MSE scores in women with vs without large cup-to-disc ratio were 95.4 ± 6 vs 96.6 ± 5. In the adjusted model, women with large cup-to-disc ratio had statistically significantly lower 3MSE scores, compared with those without large cup-to-disc ratio, yielding the predicted mean difference in 3MSE scores of 0.75 with a standard error of 0.05 units (P= .04).ConclusionsPostmenopausal women who had large cup-to-disc ratio without glaucoma or ocular hypertension exhibited lower global cognitive function. Further investigation is warranted. NOTE: Publication of this article is sponsored bythe American Ophthalmological Society.

Key Points Question Is alcohol consumption associated with the risk of dementia and cognitive decline in older adults with or without mild cognitive impairment? Findings In this cohort study of 3021 participants aged 72 years and older, alcohol intake within recommended limits was not significantly associated with a lower risk of dementia among participants with or without mild cognitive impairment at baseline. Among participants without mild cognitive impairment, daily low-quantity drinking was associated with lower dementia risk compared with infrequent higher-quantity drinking. Meaning These findings suggest that physicians caring for older adults need to carefully assess the full dimensions of drinking behavior and cognition when providing guidance to patients about their alcohol consumption., This cohort study examines the association between alcohol intake and risk of dementia among older adults with or without mild cognitive impairment., Importance Substantial heterogeneity and uncertainty exist in the observed associations between alcohol consumption and dementia. Objective To assess the association between alcohol consumption and dementia and the roles of mild cognitive impairment (MCI) and apolipoprotein E ε4 (APOE E4) genotype in modifying this association. Design, Setting, and Participants This cohort study used data from the Ginkgo Evaluation of Memory Study, conducted from 2000 to 2008 among US community-dwelling participants. This study analyzed 3021 participants aged 72 years and older who were free of dementia. Data analysis was performed from 2017 to 2018. Exposures Self-reported alcohol consumption, drinking frequency, and quantity. Main Outcomes and Measures Using multivariable proportional hazards regression and linear mixed models, the risk of dementia and the rate of change over time in the Modified Mini-Mental State Examination were estimated. Results Among 3021 participants, the median (interquartile range) age was 78 (76-80) years; 1395 (46.2%) were female. During a median (interquartile range) follow-up of 6.0 (4.9-6.5) years, 512 cases of dementia occurred. For 7.1 to 14.0 drinks per week compared with less than 1.0 drink per week, the hazard ratios for dementia were 0.63 (95% CI, 0.38-1.06) among 2548 participants without MCI and 0.93 (95% CI, 0.47-1.84) among 473 participants with MCI. Among participants with MCI, the hazard ratio for dementia was 1.72 (95% CI, 0.87-3.40) for more than 14.0 drinks per week compared with less than 1.0 drink per week. The association of alcohol intake with dementia differed for participants with and without baseline MCI (P for interaction = .03). Among participants without MCI, daily low-quantity drinking was associated with lower dementia risk than infrequent higher-quantity drinking (hazard ratio, 0.45; 95% CI, 0.23-0.89; P = .02). Findings were consistent when stratified by sex, age, and APOE E4 genotype. Compared with drinking less than 1.0 drink per week, complete abstention (in participants without MCI) and the consumption of more than 14.0 drinks per week (in participants with MCI) were associated with lower Modified Mini-Mental State Examination scores (mean difference at follow-up compared with baseline, −0.46 point [95% CI, −0.87 to −0.04 point] and −3.51 points [95% CI, −5.75 to −1.27 points], respectively). Conclusions and Relevance In this study, complete abstention and consuming more than 14.0 drinks per week (compared with drinking

Background We examined common patterns of home environmental modification (HEM) use and associated major (including disability-, cardiovascular-, and cancer-related) health conditions and events among older women. Methods Women, aged 78.6 ± 6.3 years (n = 71,257), self-reported utilization of nine types of HEMs (hand rails, grab bars, ramps, nonslip surfaces, tacking carpets/rugs, decreasing clutter, increasing lighting, raised sink/counter heights, other). Concurrent history of major health conditions and events was collected. Odds ratios (ORs) were estimated based on overall HEM use and four latent classes (low HEM use [56%], rails/grab bars [20%], lighting/decluttering [18%], high HEM use [5%]), adjusted for age, marital status, race/ethnicity, education, depression, and obesity. Results Fifty-five percent of women reported using any HEM (overall), with strongest associations among disability-related conditions. Activities of daily living limitations were strongly associated with high HEM use (OR = 8.16, 95% confidence interval [CI] = 6.62–10.05), railing/grab bar use (OR = 4.02, 95% CI = 3.26–4.95), and lighting/declutter use (OR = 1.87, 95% CI = 1.40–2.50) versus low HEM use. Recent falls were positively associated with overall HEM use (OR = 1.79, 95% CI = 1.72–1.87); high HEM use (OR = 2.89, 95% CI = 2.64–3.16), railings/grab bars use (OR = 2.32, 95% CI = 2.18–2.48), and lighting/declutter use (OR = 1.93, 95% CI = 1.79–2.08) were positively associated with recent falls. Modest associations were observed between HEM use and select (ie, atrial fibrillation, heart valve disease, stroke) cardiovascular outcomes. Conclusions Among older women, disability-related conditions, including functional limitations and recent falls, were strongly associated with overall HEM use, high HEM use, and railings/grab bar use.

OBJECTIVES As people age and the incidence of dementia increases, studies of cognitive function continue to be of importance. Ascertaining cognitive data through different mechanisms is necessary to address missing data concerns. METHODS The Dementia Questionnaire (DQ), which utilizes proxy-based assessments, is a potential tool to determine cognitive status in participants no longer being followed per traditional study protocol. The DQ is currently being used in the Supplemental Case Ascertainment Protocol (SCAP), which is being conducted in an ongoing study of postmenopausal women as part of the Women's Health Initiative Memory Study (WHIMS). RESULTS Ninety-four percent of the 1260 SCAP participants were eligible because of being deceased. Those who are SCAP eligible were older, were less likely to be a minority, and were more likely to have hypertension, diabetes, and prior history of cardiovascular disease (CVD) as well as being a past or current smoker. SCAP added 109 cases of probable dementia to WHIMS. Risk factor relationships were modified upon inclusion of the SCAP cases including an attenuation of a hormone therapy effect and discovery of a hypertension effect. CONCLUSIONS Augmenting clinic-based cases with proxy-based assessments is feasible and leads to increased incident cases of dementia. When planning future clinical trials, it may be of study benefit to include a protocol of proxy-based assessments, develop strong relationships with proxies early on in the study, and attempt to maintain this relationship throughout the lifespan of the trial.

Objective Although brain radiation therapy (RT) impacts cognitive function, little is known about the subset of survivors with minimal cognitive deficits. This study compares the characteristics of patients receiving brain irradiation as part of cancer treatment with minimal cognitive deficits to those with poorer cognitive functioning. Methods Adults at least 6 months postbrain RT (N = 198) completed cognitive measures of attention, memory, and executive functions. Cognitive functioning was categorized into better- and poorer-performing groups, with better-performing survivors scoring no worse than 1.5 standard deviations below the published normative mean on all cognitive measures. Logistic regression was used to identify variables associated with better-performing group membership. Results Approximately 25% of the sample met the criteria for the better-performing group. In unadjusted analyses, RT type (whole brain irradiation and partial brain irradiation), sedating medications, and fatigue were independently associated with cognition. Sociodemographic and other clinical characteristics were not significant. In adjusted analyses, only fatigue remained significantly associated with group membership (OR = 1.05, 95% CI = 1.01-1.09, P = .009). Conclusions There is a subgroup of survivors with minimal long-term cognitive deficits despite undergoing a full course of brain RT as part of cancer treatment. Lower fatigue had the strongest association with better cognitive performance. Interventions targeting cancer-related fatigue may help buffer the neurotoxic effects of brain RT.

Objectives Relatively few APOE e4+ carriers survive to old age (age 80+) without cognitive impairment (CI); thus, little is known about distinguishing characteristics of resilient APOE e4+ carriers. Herein, we describe the sociodemographic characteristics of a large sample of resilient APOE e4+ women from the Women's Health Initiative Memory Study (WHIMS) and compare them to noncarriers and APOE e4+ women who developed CI before age 80. Methods Women were recruited for clinical trials evaluating postmenopausal hormone therapy and incidence of dementia. During posttrial follow-up, cognitive status was adjudicated annually. Among 5716 women, we compared groups by APOE e4 status using logistic regression, covarying for treatment, demographics, lifestyle, cardiovascular and physical function, well-being, and self-rated general health. Results Among 557 APOE e4+ women, those who survived to age 80+ without CI had higher baseline self-rated general health (odds ratio [OR]: 1.02; 95% confidence interval [CI], 1.01-1.04) and cognitive scores (OR: 1.18; 95% CI, 1.12-1.25) than those who did not reach age 80 without CI. Baseline high total cholesterol and low-density lipoprotein (LDL) levels were similar across APOE e4+ groups but were higher compared with APOE e4- women. Among women who survived to 80+ without CI, more APOE e4+ women had a history of high total cholesterol (P = .003) and LDL cholesterol (OR: 1.01; 95% CI, 1.00-1.01). There were no differences in hypertension, diabetes, or other vascular risk factors in APOE e4+ women compared with noncarriers. Conclusions Results highlight the importance of baseline cognitive function and general health for late-life cognition among e4+ women.

We examined whether neighborhood built environment (BE) and cognition associations in older adults vary by apolipoprotein E (APOE) genotype, a genetic risk factor for Alzheimer's disease (AD). We conducted a cross-sectional analysis of 4091 participants. Neighborhood characteristics included social and walking destination density (SDD, WDD), intersection density, and proportion of land dedicated to retail. Individuals were categorized as APOE e2 (lower AD risk), APOE e4 (higher AD risk), or APOE e3 carriers. Among APOE e2 carriers, greater proportion of land dedicated to retail was associated with better global cognition, and greater SDD, WDD, intersection density, and proportion of land dedicated to retail was associated with better processing speed. These associations were not observed in APOE e3 or e4 carriers. APOE e2 carriers may be more susceptible to the potentially beneficial effects of denser neighborhood BEs on cognition; however, longitudinal studies are needed.