The Systolic Blood Pressure Intervention Trial suggested that intensive lowering of systolic blood pressure (SBP) decreases the risk of developing dementia. However, an insufficient number of probable dementia cases stemming from the trial's early termination made results inconclusive. The goal of this study was to estimate the effect of intensive vs standard SBP lowering on the longer term incidence of cognitive impairment leveraging extended follow-up for cognitive status. This is a prespecified secondary analysis of a randomized clinical trial. Between 2010 and 2013, patients aged 50 years and older with hypertension and increased cardiovascular risk excluding those with diabetes mellitus or history of stroke were recruited from 102 clinics in the United States and Puerto Rico. Participants were randomized to a SBP goal of <120 mm Hg (intensive treatment) or <140 mm Hg (standard treatment) and received treatment for 3.3 years. In-person cognitive assessment follow-up occurred through July 2018. Continued ascertainment of cognitive status by telephone began in December 2019 for participants who had not withdrawn consent or been previously adjudicated with probable dementia, but provided consent for future research. Data were analyzed using survival analyses. Of 9,361 randomized participants, 7,221 (77%) were eligible to be re-contacted. Cognitive status of 4,232 (59%) was ascertained (mean age 67 years, 36% female). We accrued a total of 216 new cases of probable dementia, less than our target of 326. Over a median follow-up of 7 years, 248 participants of the intensive treatment group (8.5 per 1,000 person-years) were adjudicated with probable dementia, compared with 293 participants (10.2 per 1,000 person-years) in the standard treatment group (hazard ratio [HR], 0.86; 95% CI, 0.72-1.02). Consistent with earlier results from the trial, the rate of both mild cognitive impairment (MCI; HR, 0.87 95% CI, 0.76-1.00) and a composite of MCI or probable dementia was lower with intensive treatment (HR, 0.89; 95% CI, 0.79, 0.99). Among ambulatory adults with hypertension and high cardiovascular risk, intensive treatment vs standard treatment of SBP for 3.3 years resulted in a lower risk of MCI and cognitive impairment including MCI or probable dementia, but not for probable dementia alone. This study provides Class II evidence that intensively reducing SBP (target <120 mm Hg) decreases the risk of cognitive impairment in individuals aged 50 years and older with hypertension. Clinical trial number NCT01206062.
Both high or low plasma amyloid levels have been associated with risk of dementia in nondemented subjects.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.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.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.
Identifying a safe, affordable, and well-tolerated intervention that prevents or delays cognitive decline in older adults is critically important. There is growing evidence from basic science and small randomized trials that cocoa flavanols may provide protection against cognitive decline. COSMOS-MIND is an ancillary study to the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), a large randomized controlled trial with more than 21000 participants. COSMOS-MIND examines the potential cognition-protecting effects of 3 years of treatment with cocoa flavanol extract (600mg/d), with and without co-administration of a standard multivitamin, concurrently with the evaluation of cardiovascular disease and cancer endpoints in the parent COSMOS trial. COSMOS-MIND uses validated telephone interviews to test whether these supplements improve cognitive function (or slow its decline). Proxy interviews are conducted for participants scoring below cognitive thresholds to inform adjudication of the study’s cognitive impairment outcomes, including mild cognitive impairment, Alzheimer’s and other forms of dementia. COSMOS-MIND enrolled 2,282 randomized participants (60% women), median [range] age 73 [65–94] years. Its composite primary outcome is based on scores from standardized telephone assessments of memory, executive function, and global cognitive function. We used percentile regression to portray its relationships with baseline age. The observed trajectories demonstrate that the battery is sensitive to age-related differences. Data from additional baseline measures of subjective memory problems, depression, and insomnia will be presented. COSMOS-MIND demonstrates that large simple trials with cognitive and dementia outcomes derived from telephone interviews are feasible, and may serve as a model for future clinical trials testing well-tolerated interventions.
Abstract Background The association of cognitive function with symptoms of psychological distress during the coronavirus disease 2019 (COVID-19) pandemic or adherence to COVID-19 protective health behaviors is not well-understood. Methods We examined 2 890 older women from the Women’s Health Initiative cohort. Prepandemic (ie, within 12 months prior to pandemic onset) and peripandemic global cognitive function scores were assessed with the modified Telephone Interview for Cognitive Status (TICS-m). Anxiety, stress, and depressive symptom severity during the pandemic were assessed using validated questionnaires. We examined adherence to protective behaviors that included safe hygiene, social distancing, mask wearing, and staying home. Multivariable models were adjusted for age, race, ethnicity, education, region of residence, alcohol intake, and comorbidities. Results Every 5-point lower prepandemic TICS-m score was associated with 0.33-point mean higher (95% confidence interval [CI], 0.20, 0.45) perceived stress and 0.20-point mean higher (95% CI, 0.07, 0.32) depressive symptom severity during the pandemic. Higher depressive symptom severity, but not anxiety or perceived stress, was associated with a 0.69-point (95% CI, −1.13, −0.25) mean decline in TICS-m from the prepandemic to peripandemic period. Every 5-point lower peripandemic TICS-m score was associated with 12% lower odds ratio (OR, 0.88; 95% CI, 0.80, 0.97) of practicing safe hygiene. Conclusions Among older women, we observed that: (a) lower prepandemic global cognitive function was associated with higher stress and depressive symptom severity during the pandemic; (b) higher depressive symptom severity during the pandemic was associated with cognitive decline; and (c) lower global cognitive function during the pandemic was associated with lower odds of practicing safe hygiene.
OBJECTIVES: To determine whether small decrements in global cognitive function that conjugated equine estrogen (CEE) therapies have been shown to produce in older women persist after cessation and extend to specific cognitive domains. DESIGN: Randomized controlled clinical trial. SETTING: Fourteen clinical centers of the Women's Health Initiative. PARTICIPANTS: Two thousand three hundred four women aged 65 to 80 free of probable dementia at enrollment. INTERVENTION: CEE 0.625 mg/d with or without medroxyprogesterone acetate (MPA, 10 mg/d) and matching placebos. MEASUREMENTS: Annual administrations of a battery of cognitive tests during and after the trial. RESULTS: Assignment to CEE‐based therapies was associated with small mean relative decrements in global cognitive function and several domain‐specific cognitive functions during the trial, which largely persisted through up to 4 years after the trial. The strongest statistical evidence was for global cognitive function (0.07–standard deviation decrements during ( P =.007) and after ( P =.01) the trial. For domain‐specific scores, the mean decrements were slightly smaller, were less significant, and tended to be larger for CEE‐alone therapy. CONCLUSION: CEE‐based therapies, when initiated after the age of 65, produce a small broad‐based decrement in cognitive function that persists after their use is stopped, but the differences in cognitive function are small and would not be detectable or have clinical significance for an individual woman. Differences in effects between cognitive domains suggest that more than one mechanism may be involved.
Objective: Face-to-face administration is the “gold standard” for both research and clinical cognitive assessments. However, many factors may impede or prevent face-to-face assessments, including distance to clinic, limited mobility, eyesight, or transportation. The COVID19 pandemic further widened gaps in access to care and clinical research participation. Alternatives to face-to-face assessments may provide an opportunity to alleviate the burden caused by both the COVID-19 pandemic and longer standing social inequities. The objectives of this study were to develop and assess the feasibility of a telephone- and video-administered version of the Uniform Data Set (UDS) v3 cognitive batteries for use by NIH-funded Alzheimer’s Disease Research Centers (ADRCs) and other research programs. Participants and Methods: Ninety-three individuals (M age: 72.8 years; education: 15.6 years; 72% female; 84% White) enrolled in our ADRC were included. Their most recent adjudicated cognitive status was normal cognition (N=44), MCI (N=35), mild dementia (N=11) or other (N=3). They completed portions of the UDSv3 cognitive battery, plus the RAVLT, either by telephone or video-format within approximately 6 months (M:151 days) of their annual in-person visit, where they completed the same in-person cognitive assessments. Some measures were substituted (Oral Trails for TMT; Blind MoCA for MoCA) to allow for phone administration. Participants also answered questions about the pleasantness, difficulty level, and preference for administration mode. Cognitive testers provided ratings of perceived validity of the assessment. Participants’ cognitive status was adjudicated by a group of cognitive experts blinded to most recent inperson cognitive status. Results: When results from video and phone modalities were combined, the remote assessments were rated as pleasant as the inperson assessment by 74% of participants. 75% rated the level of difficulty completing the remote cognitive assessment the same as the in-person testing. Overall perceived validity of the testing session, determined by cognitive assessors (video = 92%; phone = 87.5%), was good. There was generally good concordance between test scores obtained remotely and in-person (r = .3 -.8; p < .05), regardless of whether they were administered by phone or video, though individual test correlations differed slightly by mode. Substituted measures also generally correlated well, with the exception of TMT-A and OTMT-A (p > .05). Agreement between adjudicated cognitive status obtained remotely and cognitive status based on in-person data was generally high (78%), with slightly better concordance between video/in-person (82%) vs phone/in-person (76%). Conclusions: This pilot study provided support for the use of telephone- and video-administered cognitive assessments using the UDSv3 among individuals with normal cognitive function and some degree of cognitive impairment. Participants found the experience similarly pleasant and no more difficult than inperson assessment. Test scores obtained remotely correlated well with those obtained in person, with some variability across individual tests. Adjudication of cognitive status did not differ significantly whether it was based on data obtained remotely or in-person. The study was limited by its’ small sample size, large test-retest window, and lack of randomization to test-modality order. Current efforts are underway to more fully validate this battery of tests for remote assessment. Funded by: P30 AG072947 & P30 AG049638-05S1
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.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.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.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.
