Randomized double-masked controlled trial of cognitive training in breast cancer survivors: a preliminary study.

PURPOSE: To evaluate the acceptability, satisfaction, and preliminary efficacy of cognitive training for improving cognitive function and health outcomes in breast cancer survivors (BCS). PATIENTS AND METHODS: BCS enrolled in this 2-group randomized, double-masked controlled trial of cognitive training. Primary outcomes included the acceptability and satisfaction of the interventions. Secondary outcomes included examining the effect size and reliable improvement of perceived cognitive function and health outcomes, including work ability, health perception (status and change), and quality of life. Exploratory outcomes were performance on neuropsychological tests and plasma levels of brain-derived neurotropic factor (BDNF). Data were collected at baseline and immediately post-intervention. Using ANCOVA models, the intervention was compared to attention control while adjusting for covariates and baseline values. The effect sizes for differences in means and the reliable improvement percentage were reported. RESULTS: Thirty-six BCS completed the study and were on average 57.6 (SD = 8.0) years old, 59.4% Caucasian, and had some college education (74.5%). Both programs were reported to be satisfactory and acceptable. Non-significant small effect sizes were noted for the intervention on cognitive abilities (d = 0.26) and cognitive concerns (d = - 0.32), with reliable improvement noted in 32% and 28% of BCS, respectively. Small to medium effect sizes were noted in improvement in work ability (d = 0.37) and health perception status (d = 0.30) and change (d = 0.60, p < 0.05). CONCLUSIONS: Cognitive training was acceptable to BCS and resulted in improvement in perceived cognitive function and perceptions of "real-world" health benefits. A larger randomized controlled trial is warranted to determine its effectiveness for objective cognitive performance.

Lifecourse socioeconomic position and diabetes incidence in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, 2003 to 2016.

Low socioeconomic position (SEP) across the lifecourse is associated with Type 2 diabetes (T2DM). We examined whether these economic disparities differ by race and sex. We included 5448 African American (AA) and white participants aged ≥45 years from the national (United States) REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort without T2DM at baseline (2003-07). Incident T2DM was defined by fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or using T2DM medications at follow-up (2013-16). Derived SEP scores in childhood (CSEP) and adulthood (ASEP) were used to calculate a cumulative (CumSEP) score. Social mobility was defined as change in SEP. We fitted race-stratified logistic regression models to estimate the association between each lifecourse SEP indicator and T2DM, adjusting for covariates; additionally, we tested SEP-sex interactions. Over a median of 9.0 (range 7-14) years of follow-up, T2DM incidence was 167.1 per 1000 persons among AA and 89.9 per 1000 persons among white participants. Low CSEP was associated with T2DM incidence among AA (OR = 1.61; 95%CI 1.05-2.46) but not white (1.06; 0.74-2.33) participants; this was attenuated after adjustment for ASEP. In contrast, low CumSEP was associated with T2DM incidence for both racial groups. T2DM risk was similar for stable low SEP and increased for downward mobility when compared with stable high SEP in both groups, whereas upward mobility increased T2DM risk among AAs only. No differences by sex were observed. Among AAs, low CSEP was not independently associated with T2DM, but CSEP may shape later-life experiences and health risks.

Vascular-brain Injury Progression after Stroke (VIPS) study: concept for understanding racial and geographic determinants of cognitive decline after stroke.

Cognitive impairment and dementia (CID) are major public health problems with substantial personal, social, and financial burdens. African Americans are at a heightened risk for Vascular Cognitive Impairment (VCI) compared to European Americans. Recent lines of evidence also suggest a high burden of Post-stroke VCI among indigenous Africans. A better understanding of the cause(s) of the racial disparity in CID, specifically VCI, is needed in order to develop strategies to reduce it. We propose and discuss the conceptual framework for a unique tri-population, trans-continental study titled The Vascular brain Injury Progression after Stroke (VIPS) study. The overarching objective of the VIPS Study will be to explore the interplay of multiple factors (racial, geographical, vascular, lifestyle, nutritional, psychosocial and inflammatory) influencing the level and trajectory of post-stroke cognitive outcomes and examine whether differences between indigenous Africans, African Americans and European Americans exist. We hypothesize that differences which might be due to racial factors will be observed in African Americans versus European Americans as well as Indigenous Africans versus European Americans but not in African Americans versus Indigenous Americans; differences due to geographical factors will be observed in Indigenous Americans versus African Americans and Indigenous Africans versus European Americans but not in African Americans versus European Americans. This overarching objective could be accomplished by building upon existing National Institutes of Health investments in the REasons for Geographical And Racial Differences in Stroke (REGARDS) study (based in the United States of America) and the Stroke Investigative Research and educational Network (SIREN) study (based in Sub-Saharan Africa).

Galectin-3 and incident cognitive impairment in REGARDS, a cohort of blacks and whites.

INTRODUCTION: The relationship between serum galectin-3 and incident cognitive impairment was analyzed in the Reasons for Geographic and Racial Differences in Stroke study. METHODS: Baseline galectin-3 was measured in 455 cases of incident cognitive impairment and 546 controls. Galectin-3 was divided into quartiles based on the weighted distribution in the control group, and the first quartile was the referent. RESULTS: There was an increasing odds of cognitive impairment across quartiles of galectin-3 (odds ratios, 1.00 [0.68-1.46], 1.45 [1.01-2.10], and 1.58 [1.10-2.27] relative to the quartile 1; P trend = .003) in an unadjusted model, which persisted after adjusting for age, sex, and race (P = .004). Adjustment for cardiovascular risk factors greatly attenuated this association (odds ratios, 0.97 [0.60-1.57], 1.52 [0.94-2.46], and 1.27 [0.76-2.12]; P = .15). The association differed by diabetes status (P interaction, .007). Among nondiabetics (293 cases, 411 controls), those with galectin-3 in the fourth compared with first quartile had an odds ratio of 1.6 (0.95-2.99; P trend, .02). In diabetics, the odds ratio was 0.23 (0.04-1.33). DISCUSSION: Serum galectin-3 was associated with increased risk of incident cognitive impairment in a large cohort study of blacks and whites but only in nondiabetics.

Anticholinergics Influence Transition from Normal Cognition to Mild Cognitive Impairment in Older Adults in Primary Care.

STUDY OBJECTIVE: To determine the influence of anticholinergic medications on transitions in cognitive diagnosis of older adults in primary care. DESIGN: This observational cohort study was conducted over a mean follow-up of 3.2 years. Anticholinergic exposure was defined by pharmacy dispensing and claims records. Cognitive diagnosis was performed by an expert panel at baseline and annually up to 4 years. DATA SOURCE: Medication exposure and other clinical data were extracted from the Indiana Network for Patient Care (INPC). The cognitive diagnosis was derived from a cognitive screening and diagnosis study. PARTICIPANTS: A total of 350 adults 65 years and older without dementia and receiving primary care in a safety net health care system. MEASUREMENT AND MAIN RESULTS: Cognitive diagnosis followed a two-phase screening and consensus-based neuropsychiatric examination to determine a baseline diagnosis as normal cognition, mild cognitive impairment (MCI), or dementia, with a follow-up neuropsychiatric examination and consensus-based diagnosis repeated annually. The Anticholinergic Cognitive Burden scale was used to identify anticholinergics dispensed up to 10 years before enrollment and annually throughout the study. A total standard daily dose of anticholinergics was calculated by using pharmacy dispensing data from the INPC. Among 350 participants, a total of 978 diagnostic assessments were completed over a mean follow-up of 3.2 years. Compared with stable cognition, increasing use of strong anticholinergics calculated by total standard daily dose increased the odds of transition from normal cognition to MCI (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.31, p = 0.0342). Compared with stable MCI, strong anticholinergics did not influence the reversion of MCI to normal cognition (OR 0.95, 95% CI 0.86-1.05, p = 0.3266). CONCLUSION: De-prescribing interventions in older adults with normal cognition should test anticholinergics as potentially modifiable risk factors for cognitive impairment.

Dietary patterns are associated with cognitive function in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

Identifying factors that contribute to the preservation of cognitive function is imperative to maintaining quality of life in advanced years. Of modifiable risk factors, diet quality has emerged as a promising candidate to make an impact on cognition. The objective of this study was to evaluate associations between empirically derived dietary patterns and cognitive function. This study included 18 080 black and white participants aged 45 years and older from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Principal component analysis on data from the Block98 FFQ yielded five dietary patterns: convenience, plant-based, sweets/fats, Southern, and alcohol/salads. Incident cognitive impairment was defined as shifting from intact cognitive status (score >4) at first assessment to impaired cognitive status (score ≤4) at latest assessment, measured by the Six-Item Screener. Learning, memory and executive function were evaluated with the Word List Learning, Word List Delayed Recall, and animal fluency assessments. In fully adjusted models, greater consumption of the alcohol/salads pattern was associated with lower odds of incident cognitive impairment (highest quintile (Q5) v. lowest quintile (Q1): OR 0·68; 95 % CI 0·56, 0·84; P for trend 0·0005). Greater consumption of the alcohol/salads pattern was associated with higher scores on all domain-specific assessments and greater consumption of the plant-based pattern was associated with higher scores in learning and memory. Greater consumption of the Southern pattern was associated with lower scores on each domain-specific assessment (all P < 0·05). In conclusion, dietary patterns including plant-based foods and alcohol intake were associated with higher cognitive scores, and a pattern including fried food and processed meat typical of a Southern diet was associated with lower scores.

ABO blood type, factor VIII, and incident cognitive impairment in the REGARDS cohort.

OBJECTIVE: To assess the relationships among ABO group, factor VIII (FVIII), and incident cognitive impairment in a large, prospective cohort study of black and white adults in the United States using a nested case-control design. METHODS: Incident cognitive impairment was defined using cognitive domain tests over a mean follow-up of 3.4 years. ABO blood group was measured by genotyping in a nested case-control sample of 495 cases with cognitive impairment and 587 controls. RESULTS: Those with blood group AB and those with higher FVIII had an increased risk of cognitive impairment, adjusting for age, race, region, and sex (respective odds ratios 1.82, 95% confidence interval [CI] 1.15-2.90; and 1.24, 95% CI 1.10-1.38 for 40 IU/dL higher FVIII). Mean FVIII was higher in those with blood type AB (142 IU/dL; 95% CI 119-165) compared with O (104 IU/dL; 95% CI 101-107), and FVIII mediated 18% of the association between AB group and incident cognitive impairment (95% CI for mediation -30% to 68%). CONCLUSIONS: Blood group AB and higher FVIII were associated with increased incidence of cognitive impairment in this prospective study. The association of blood group AB with incident cognitive impairment was not significantly mediated by FVIII levels.

Risk factors for the progression of mild cognitive impairment to dementia.

The increasing prevalence of cognitive impairment among the older adult population warrants attention to the identification of practices that may minimize the progression of early forms of cognitive impairment, including the transitional stage of mild cognitive impairment (MCI), to permanent stages of dementia. This article identifies both markers of disease progress and risk factors linked to the progression of MCI to dementia. Potentially modifiable risk factors may offer researchers a point of intervention to modify the effect of the risk factor and to minimize the future burden of dementia.

Advanced cognitive training for breast cancer survivors: a randomized controlled trial.

The purpose of this study was to evaluate the preliminary efficacy and satisfaction/acceptability of training in memory or speed of processing versus wait-list control for improving cognitive function in breast cancer survivors. 82 breast cancer survivors completed a three-group randomized, controlled trial. Primary outcomes were objective neuropsychological tests of memory and speed of processing. Secondary outcomes were perceived cognitive functioning, symptom distress (mood disturbance, anxiety, and fatigue), quality of life, and intervention satisfaction/acceptability. Data were collected at baseline, post-intervention, and 2-month follow-up. Using repeated-measures mixed-linear ANCOVA models, each intervention was compared to wait-list control while adjusting for age, education, and baseline measures. The effect sizes for differences in means and the reliable improvement percentage were reported. The results show that domain-specific effects were seen for both interventions: memory training improved memory performance at 2-month follow-up (p = 0.036, d = 0.59); speed of processing training improved processing speed post-intervention (p = 0.040, d = 0.55) and 2-month follow-up (p = 0.016; d = 0.67). Transfer effects to non-trained domains were seen for speed of processing training with improved memory post-intervention (p = 0.007, d = 0.75) and 2-month follow-up (p = 0.004, d = 0.82). Both interventions were associated with improvements in perceived cognitive functioning, symptom distress, and quality of life. Ratings of satisfaction/acceptability were high for both interventions. It was concluded that while both interventions appeared promising, speed of processing training resulted in immediate and durable improvements in objective measures of processing speed and verbal memory. Speed of processing training may have broader benefits in this clinical population.

Medication adherence in older adults with cognitive impairment: a systematic evidence-based review.

BACKGROUND: Cognitive impairment challenges the ability to adhere to the complex medication regimens needed to treat multiple medical problems in older adults. OBJECTIVE: Our aim was to conduct a systematic evidence-based review to identify barriers to medication adherence in cognitively impaired older adults and interventions aimed at improving medication adherence. METHODS: A search of MEDLINE, EMBASE, PsycINFO, GoogleDocs, and CINAHL for articles published between 1966 and February 29, 2012 was performed. Studies included older adults with a diagnosis of cognitive impairment of any degree (mild cognitive impairment or mild, moderate, or severe dementia). To identify barriers to adherence, we reviewed observational studies. To identify relevant interventions, we reviewed clinical trials targeting medication adherence in cognitively impaired older adults. We excluded studies lacking a measure of medication adherence or lacking an assessment of cognitive function, case reports or series, reviews, and those focusing on psychiatric disorders or infectious diseases. Population demographics, baseline cognitive function, medication adherence methods, barriers to adherence, and prospective intervention methodologies were extracted. RESULTS: The initial search identified 594 articles. Ten studies met inclusion criteria for barriers to adherence and three met inclusion criteria for interventional studies. Unique barriers to adherence included understanding new directions, living alone, scheduling medication administration into the daily routine, using potentially inappropriate medications, and uncooperative patients. Two studies evaluated reminder systems and showed no benefit in a small group of participants. One study improved adherence through telephone and televideo reminders at each dosing interval. The results of the review are limited by reviewing only published articles, missing barriers or interventions due to lack of subgroup analysis, study selection and extraction completed by 1 reviewer, and articles with at least an abstract published in English. CONCLUSIONS: The few studies identified limit the assessment of barriers to medication adherence in the cognitively impaired population. Successful interventions suggest that frequent human communication as reminder systems are more likely to improve adherence than nonhuman reminders.

Behavioral symptoms in community-dwelling elderly Nigerians with dementia, mild cognitive impairment, and normal cognition.

BACKGROUND: Few studies have examined the neuropsychiatric status of patients with dementia and cognitive impairment in the developing world despite the fact that current demographic trends suggest an urgent need for such studies. OBJECTIVE: To assess the level of neuropsychiatric symptoms in community-dwelling individuals with dementia, cognitive impairment no dementia and normal cognition. METHODS: Subjects were from the Ibadan site of Indianapolis-Ibadan Dementia Project with stable diagnoses of normal cognition, cognitive impairment, no dementia/mild cognitive impairment (CIND/MCI), and dementia. Informants of subjects made ratings on the neuropsychiatric inventory and blessed dementia scale; subjects were tested with the mini mental state examination. RESULTS: One hundred and eight subjects were included in the analytic sample, 21 were cognitively normal, 34 were demented, and 53 were CIND/MCI. The diagnostic groups did not differ in age, per cent female, or per cent with any formal education. The most frequent symptoms among subjects with CIND/MCI were depression (45.3%), apathy (37.7%), night time behavior (28.3%), appetite change (24.5%), irritability (22.6%), delusions (22.6%), anxiety (18.9%), and agitation (17.0%). Depression was significantly more frequent among the CIND/MCI and dementia (44.1%) groups compared with the normal cognition group (9.5%). Distress scores were highest for the dementia group, lowest for the normal cognition group, and intermediate for the CIND/MCI group. CONCLUSION: Significant neuropsychiatric symptomatology and distress are present among cognitively impaired persons in this community-based study of older adults in this sub-Saharan African country. Programs to assist family members of cognitively impaired and demented persons should be created or adapted for use in developing countries.

Albuminuria, kidney function, and the incidence of cognitive impairment among adults in the United States.

BACKGROUND: Albuminuria and estimated glomerular filtration rate (eGFR) are each associated with increased risk of cognitive impairment, but their joint association is unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A US national sample of 19,399 adults without cognitive impairment at baseline participating in the REGARDS (Reasons for Geographic and Racial Disparities in Stroke) Study. PREDICTORS: Albuminuria was assessed using urine albumin-creatinine ratio (UACR) and GFR was estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. OUTCOMES: Incident cognitive impairment was defined as score ≤4 on the 6-Item Screener at the last follow-up visit. RESULTS: During a mean follow-up of 3.8 ± 1.5 years, UACRs of 30-299 and ≥300 mg/g were associated independently with 31% and 57% higher risk of cognitive impairment, respectively, relative to individuals with UACR <10 mg/g. This finding was strongest for those with high eGFRs and attenuated at lower levels (P = 0.04 for trend). Relative to eGFR ≥60 mL/min/1.73 m(2), eGFR <60 mL/min/1.73 m(2) was not associated independently with cognitive impairment. However, after stratifying by UACR, eGFR <60 mL/min/1.73 m(2) was associated with a 30% higher risk of cognitive impairment in participants with UACR <10 mg/g, but not higher UACRs (P = 0.04 for trend). LIMITATIONS: Single measures of albuminuria and eGFR, screening test of cognition. CONCLUSIONS: When eGFR was preserved, albuminuria was associated independently with incident cognitive impairment. When albuminuria was <10 mg/g, low eGFR was associated independently with cognitive impairment. Albuminuria and low eGFR are complementary, but not additive, risk factors for incident cognitive impairment.

A comparative study to screen dementia and APOE genotypes in an ageing East African population.

Previous studies have established cross-cultural methods to screen for ageing- related dementia and susceptibility genes, in particular Alzheimer's disease (AD) among the Canadian Cree, African Americans and Yoruba in Nigeria. We determined whether the Community Screening Interview for Dementia (CSID), translated into Kikuyu, a major language of Kenya, could be used to evaluate dementia of the Alzheimer type. Using two sets of coefficients of cognitive and informant scores, two discriminant function (DF) scores were calculated for each of 100 elderly (>65 years) Nyeri Kenyans. When the cut-off points were selected for 100% sensitivities, the specificities of the DF scores were remarkably similar (93.75%) in the Kenyan sample. We propose the adapted CSID can be utilised to detect dementia among East Africans. We also show that apolipoprotein E epsilon 4 allele frequencies were high (approximately 30%) and not different between normal subjects and those with probable AD. There was no evidence to suggest years of education or vascular factors were associated with dementia status.

Who refuses the diagnostic assessment for dementia in primary care?

OBJECTIVE: Early screening and detection of dementia in primary care remains controversial. At least half of the patients identified as cognitively impaired by screening instruments do not meet criteria for dementia and some patients refuse further evaluation following a positive screen. The aim of this study was to identify the characteristics of patients who refuse a clinical diagnostic assessment for dementia after screening. DESIGN: Cross sectional study. SETTING: Seven primary care practice centers in Indianapolis. PARTICIPANTS: Four hundred and thirty-four individuals aged 65 and older who screened positive for dementia with a mean age of 74.6, 67% women, and 68% African-American. MAIN OUTCOME MEASURE: Patients' acceptance of undergoing a dementia diagnostic assessment that included neuropsychological testing, caregiver interview, and medical chart review. RESULTS: Among patients with positive screening results for dementia, approximately half (47.7%) refused further assessment to confirm their screening results. In a bivariate analysis, possible factors associated with a higher probability of refusing dementia assessment were older age and better screening score. In a multiple logistic regression model, performing well on the temporal orientation of the screening instrument was associated with a higher probability of refusing diagnostic assessment for dementia (OR = 1.37; p = 0.001). Also, African-American patients aged 80 and older were more likely to refuse the diagnostic assessment than African-Americans less than 80 years of age (OR = 3.1, p < 0.001), while there was no significant age association for white patients (OR = 0.9, p = 0.728). CONCLUSIONS: Older primary care patients who perceived themselves as having no cognitive symptoms refused dementia diagnostic assessment despite their positive screening results. We must improve our understanding of the decision-making process driving patients' beliefs and behaviors about the benefits and risks of dementia screening and diagnosis before implementing any broad-based screening initiatives for dementia.

Effects of stimulus predictability and interstimulus gap on saccades in Alzheimer's disease.

OBJECTIVES: Studies of saccadic eye movement impairment in Alzheimer's disease (AD) have largely focused on simple reflexive eye movements and the antisaccade task. The effects of manipulating stimulus timing have been little studied. METHODS: Fourteen patients with mild to severe AD and 11 age-matched controls were studied on the antisaccade task, while latencies on simultaneous, gap and predictable tasks were recorded from 11 patients and 11 controls. Dementia severity was assessed with the Mini-Mental State Examination. RESULTS: As a group, patients' latencies were significantly higher and more variable on the simultaneous and gap tasks. Predictable task performance was similar in mean but significantly more variable. Grossly anticipatory responses by patients were common on the predictable, simultaneous and gap tasks. Exclusion of these from subject means revealed that AD patients, when making target-driven saccades, demonstrated a gap effect of similar magnitude to normal subjects. Patients made significantly fewer correct antisaccades and significantly more reflexive errors not followed by a corrective antisaccade than did controls. CONCLUSIONS: The frequent presence of grossly anticipatory saccades may reflect dysfunction of fixation mechanisms possibly involving projections from frontal lobe to superior colliculus. The less frequently seen, marked prolongation of latency may reflect changes in posterior parietal mechanisms mediating reflexive saccade generation. The presence of the gap effect demonstrates a continued ability to benefit from externally controlled stimulus disengagement. Patients' ability to make appropriately timed saccades to targets of known locations was particularly impaired, but the target sequence itself was at least grossly correctly learned. Larger studies may be able to identify clinically distinct populations of AD patients.