Trajectories of peripheral interleukin-6, structure of the hippocampus, and cognitive impairment over 14 years in older adults.

We aimed to investigate if trajectory components (baseline level, slope, and variability) of peripheral interleukin-6 (IL-6) over time were related to cognitive impairment and smaller hippocampal volume and if hippocampal volume explained the associations between IL-6 and cognitive impairment. Multivariable regression models were used to test the association between IL-6 trajectory components with change in neuroimaging measures of the hippocampus and with cognitive impairment among 135 older adults (70-79 years at baseline) from the Healthy Brain Project over 14 years. IL-6 variability was positively associated with cognitive impairment (odds ratio [OR] = 5.86, 95% confidence interval [CI]: 1.24, 27.61) and with greater decrease per year of gray matter volume of the hippocampus (ß = -0.008, standard error = 0.004, p = 0.03). After adjustment for hippocampal volume, the OR of cognitive impairment decreased for each unit of IL-6 variability and CIs widened (OR = 4.36, 95% CI: 0.67, 28.29). Neither baseline levels nor slopes of IL-6 were related to cognitive impairment or hippocampal volume. We believe this has potential clinical and public health implications by suggesting adults with stable levels of peripheral IL-6 may be better targets for intervention studies for slowing or preventing cognitive decline.

Classification of amyloid-positivity in controls: comparison of visual read and quantitative approaches.

UNLABELLED: An important research application of amyloid imaging with positron emission tomography (PET) is detection of the earliest evidence of fibrillar amyloid-beta (Aß) deposition. Use of amyloid PET for this purpose, requires a reproducible method for defining a cutoff that separates individuals with no significant Aß deposition from those in which Aß deposition has begun. We previously reported the iterative outlier approach (IO) for the analysis of Pittsburgh Compound-B (PiB) PET data. Developments in amyloid imaging since the initial report of IO have led us to re-examine the generalizability of this method. IO was developed using full-dynamic atrophy-corrected PiB PET data obtained from a group of control subjects with a fairly distinct separation between PiB-positive [PiB(+)] and PiB-negative [PiB(-)] subjects. METHODS: We tested the performance of IO using late-summed tissue ratio data with atrophy correction or with an automated template method without atrophy correction and tested the robustness of the method when applied to a cohort of older subjects in which separation between PiB(+) and PiB(-) subjects was not so distinct. RESULTS: The IO method did not perform consistently across analyses and performed particularly poorly when separation was less clear. We found that a sparse k-means (SKM) cluster analysis approach performed significantly better; performing more consistently across methods and subject cohorts. We also compared SKM to a consensus visual read approach and found very good correspondence. CONCLUSION: The visual read and SKM methods, applied together, may optimize the identification of early Aß deposition. These methods have the potential to provide a standard approach to the detection of PiB-positivity that is generalizable across centers.

Concurrent validity of a computer-based cognitive screening tool for use in adults with HIV disease.

As the incidence of HIV-associated dementia has decreased, the survival of HIV-infected individuals with milder forms of cognitive impairment has increased. Detecting this milder impairment in its earliest stages has great clinical and research importance. We report here the results of an initial evaluation of the Computer Assessment of Mild Cognitive Impairment (CAMCI(®)), a computerized screening tool designed to assess abnormal cognitive decline with reduced respondent and test administrator burden. Fifty-nine volunteers (29 HIV infected; age=50.9 years; education=14.9 years; 36/59 males) completed the CAMCI(®) and a battery of neuropsychological tests. The CAMCI was repeated 12 and 24 weeks later. The results from the CAMCI were compared to Global and Domain Impairment scores derived from the full neuropsychological test battery. The CAMCI detected mild impairment (compared with normal and borderline test performance) with a sensitivity of 0.72, specificity of 0.97, positive predictive rate of 0.93, and a negative predictive rate of 0.89. Median stability over 12 and 24 weeks of follow-up was 0.32 and 0.46, respectively. These rates did not differ as a function of serostatus. A discriminant function analysis correctly classified 90% of the subjects with respect to their overall Global Impairment Rating from six of the CAMCI scores. This preliminary study demonstrates that the CAMCI is sensitive to mild forms of cognitive impairment, and is stable over 24 weeks of follow-up. A larger trial to obtain risk-group appropriate normative data will be necessary to make the instrument useful in both clinical practice and research (e.g., clinical trials).

Exploring the reasons urban and rural-dwelling older adults participate in memory research.

This study examines how underrepresented older urban and rural-dwelling individuals conceptualize participation in cognitive impairment studies. Nine focus groups were held with urban and rural-dwelling older adults who had participated in a community-based memory screening study. Expected and experienced benefits of research participation were motivators for study participation in all focus groups. Results indicate that participation in memory research was believed to lead to an understanding of memory function. Focus group participants expressed an active interest in research on dementia, and viewed research participation as a way to address memory concerns and provide a benefit to society.

Cross-cultural comparisons of the Mini-mental State Examination between Japanese and U.S. cohorts.

BACKGROUND: The Mini-mental State Examination (MMSE) is widely used in Japan and the U.S.A. for cognitive screening in the clinical setting and in epidemiological studies. A previous Japanese community study reported distributions of the MMSE total score very similar to that of the U.S.A. METHODS: Data were obtained from the Monongahela Valley Independent Elder's Study (MoVIES), a representative sample of community-dwelling elderly people aged 65 and older living near Pittsburgh, U.S.A., and from the Tajiri Project, with similar aims in Tajiri, Japan. We examined item-by-item distributions of the MMSE between two cohorts, comparing (1) percentage of correct answers for each item within each cohort, and (2) relative difficulty of each item measured by Item Characteristic Curve analysis (ICC), which estimates log odds of obtaining a correct answer adjusted for the remaining MMSE items, demographic variables (age, gender, education) and interactions of demographic variables and cohort. RESULTS: Median MMSE scores were very similar between the two samples within the same education groups. However, the relative difficulty of each item differed substantially between the two cohorts. Specifically, recall and auditory comprehension were easier for the Tajiri group, but reading comprehension and sentence construction were easier for the MoVIES group. CONCLUSIONS: Our results reaffirm the importance of validation and examination of thresholds in each cohort to be studied when a common instrument is used as a dementia screening tool or for defining cognitive impairment.

Factors associated with adherence to medication regimens in older primary care patients: the Steel Valley Seniors Survey.

OBJECTIVE: The aim of this study was to explore associations between 2 specific cognitive domains and aspects of medication management among older primary care patients. METHODS: A sample of patients aged >or=65 years drawn from several small-town primary care practices was carefully characterized by cognitive testing and use of prescription medications. Two primary outcome variables were examined: (1) self-reports of setting up schedules to manage their own medications and (2) overall research assessment of adherence to prescribed medications. Predictor variables included scores on tests of verbal memory (Hopkins Verbal Learning Test) and executive function (Part B of the Trail Making Test); prescription insurance status; number of medications; and dosing frequency, adjusting for age, sex, and level of education. Multiple logistic regression and generalized estimating equation models were used for multivariable analyses. RESULTS: The analytic sample included 343 patients (238 women, 105 men; mean [SD] age, 77.52 [6.71] years). Higher scores on the verbal memory test were independently associated with successfully setting up a medication schedule, after adjusting for covariates (compared with scores in the <10th percentile, odds ratio [OR] for scores between the 10th and 50th percentiles: 5.02 [95% CI, 2.22-11.33; P < 0.001]; OR for scores in the >50th percentile: 6.52 [95% CI, 2.76-15.42; P < 0.001]). Higher scores on the executive function test were associated with treatment adherence (compared with scores in the <10th percentile, OR for scores between the 10th and 50th percentiles: 3.25 [95% CI, 1.13-9.33; P = 0.03]; OR for scores in the >50th percentile: 4.32 [95% CI, 2.76-15.68; P = 0.02]). Compared with using or=5 drugs was also associated with poor adherence (OR: 0.45 [95% CI, 0.21-0.95; P = 0.04]) as measured by research nurses' assessment of adherence. CONCLUSIONS: In this sample of older patients assessed for medication management, independent cognitive processes were associated with the ability to set up a medication schedule and overall adherence to prescriptions. Better verbal memory functioning was strongly and independently associated with setting up a medication schedule, while better executive functioning was strongly and independently associated with being fully adherent to prescription instructions. Deficits in either cognitive ability could result in medication errors due to nonadherence.

Cognitive assessment of older primary care patients with and without memory complaints.

BACKGROUND: Dementia screening is currently recommended only for symptomatic patients. OBJECTIVE: To evaluate memory complaints, a mental status test, and several cognitive tests as dementia screens in primary care. DESIGN: Cross-sectional clinical epidemiologic study. PARTICIPANTS: Three hundred thirty-nine comprehensively assessed, primary care patients aged > or = 65 years. MEASUREMENTS: Memory complaints were abstracted from chart review. Scores on Mini-Mental State Examination (MMSE) and domain-specific cognitive testing were compared to a dementia diagnosis based on Clinical Dementia Rating score > or = 1, and areas under the receiver operating characteristic curves (AUC) were calculated. Classification and regression tree analyses were performed on memory complaints and tests with the highest AUCs. RESULTS: Of 33 patients with dementia, only 5 had documented memory complaints. In 25 patients with documented memory complaints, no cognitive tests further improved identification of the 5 with dementia. In 28 patients with dementia but without memory complaints, an MMSE score < 20 identified 8 cases; among those with MMSE scores 20-21, a visual memory test identified a further 11 cases. Further cognitive testing could not detect 9 dementia cases without memory complaints and with MMSE scores > or = 22. CONCLUSIONS: In older primary care patients with memory complaints, cognitive screening does not help identify those who require further examination for dementia. Most patients with dementia do not report memory complaints. In these asymptomatic individuals, general mental status testing, supplemented by a memory test when the mental status score is equivocal, will identify lower-scoring patients who need dementia assessment. However, high-scoring asymptomatic dementia cases will remain undetected.

The association between congestive heart failure and cognitive performance in a primary care population of elderly adults: the Steel Valley Seniors Survey.

BACKGROUND: Evidence suggests an association between congestive heart failure (CHF) and cognitive function, particularly in heart transplant patients and patients hospitalized for CHF. We examined the association between CHF and cognitive performance in stable outpatients recruited from primary care. METHODS: This is a cross-sectional secondary data analysis of the Steel Valley Seniors Survey, an epidemiological study of elderly primary care outpatients. Participants aged >/= 65 years were recruited in primary care clinics. The study cohort (n = 354) is a subgroup, composed of subjects with Mini-mental State Examination score < 25, and a random sample of the remaining, who underwent a baseline assessment in the home. The assessment included demographics, comorbid illnesses, depressive symptoms, functional status, a neurological examination and a neuropsychological battery. CHF is defined by self-report and/or chart review, and stable CHF as not being hospitalized in the year prior to the assessment. The associations between CHF and specific cognitive tests were examined by bivariate analysis and logistic regression, controlling for demographic variables. RESULTS: Subjects with CHF performed worse on tests of visual memory [10.1 (S.D. 5.4) vs. 12.7 (S.D. 5.2), p = 0.007], Trailmaking B [0.1 (0.1) vs. 0.2 (0.1), p = 0.002], category fluency [11.1 (4.4) vs. 13.4 (4.5), p = 0.008], and clock drawing [5.6 (1.9) vs. 6.7 (1.4), p < 0.001] compared to subjects without CHF, after adjustment for relevant demographic variables. CONCLUSION: CHF is associated with lower cognitive functioning in a population of patients with stable heart failure in primary care settings.

Detection and management of cognitive impairment in primary care: The Steel Valley Seniors Survey.

OBJECTIVES: To identify characteristics of older primary care patients who were cognitively impaired and who underwent mental status testing by their physicians. DESIGN: Cross-sectional and retrospective analysis. SETTING: Seven small-town primary care practices. PARTICIPANTS: A total of 1,107 patients with a mean+/-standard deviation age of 76.3+/-6.6, screened using the Mini-Mental State Examination (MMSE); medical records reviewed. MEASUREMENTS: Demographics, MMSE, medical record information. Odds ratios (OR) with 95% confidence intervals (CI), adjusted for age, sex, and education. RESULTS: Thirty-one percent of the sample had MMSE scores of less than 25. Among these patients, physicians documented memory loss in only 23% which was significantly more often than in the higher scoring group (OR=1.9, 95% CI=1.3-2.8), basic activity of daily living (ADL) impairment in 7.9% (OR=2.4, 95% CI=1.3-4.4), instrumental ADL (IADL) impairment in 6.7% (OR=2.2, 95% CI=1.1=4.2), dementia in 12.2% (OR=3.7, 95% CI=2.0-6.8), and prescription of cholinesterase inhibitors in 7.6% (OR=4.4, 95% CI=1.9-10.2). Physicians recorded mental status testing largely in patients with research MMSE scores of 24 to 28, significantly more often when they also documented memory loss (OR=3.8, 95% CI=2.5-5.6) or impaired IADLs (OR=2.7, 95% CI=1.4-5.2), diagnosed dementia (OR=4.9, 95% CI=2.8-8.6), referred to specialists (OR=6.3, 95% CI=2.5-16.2) or social services (OR=3.6, 95% CI=1.8-7.3), or prescribed cholinesterase inhibitors (OR=8.5, 95% CI=4.2-17.5). CONCLUSION: Physicians noted impairment in a minority of impaired patients. They tested mental status in those with documented cognitive and functional difficulties, in very mildly impaired patients, and in those for whom they intervened.