Modified Mini Mental State Exam Research Articles

THE DIFFERENCE BETWEEN CYSTATIN C- AND CREATININE-BASED EGFR AND ASSOCIATIONS WITH COGNITION IN THE CHS

Abstract The difference (eGFRDiff) between cystatin C-based estimated glomerular filtration rate (eGFRcys) and creatinine based eGFR (eGFRcr) has been shown to be associated with frailty and mortality, but its association with cognition is unclear. Among 4,764 adults aged ≥ 65 from the Cardiovascular Health Study, we analyzed eGFRDiff per 1-SD lower (18.6 mL/min/1.73m2). Cognitive function was evaluated annually using the Modified Mini Mental State Exam (3MS; range 0-100), and the Digit Symbol Substitution Test (DSST; range 0-90); higher scores mean better performance. We used linear regression for cross-sectional analyses, and mixed models for longitudinal analyses adjusted for demographic and clinical variables. The mean age was 72.2 ±, the mean eGFRDiff was 0.64, and mean follow-up was 4.4 ± years. eGFRDiff was not associated with 3MS at baseline. Each SD lower eGFRDiff at baseline was associated with a 0.82 [95% CI: -1.22, -0.42] lower DSST score. In longitudinal analyses each SD lower eGFRDiff was associated with a significant 0.06 [95% CI: -0.11, -0.01] faster decline in 3MS scores and a 0.04 [95% CI: -0.08, -0.01] faster decline in DSST scores over time. In older adults, we found that lower eGFRDiff was associated with lower cognitive scores at baseline, and associated with more rapid decline over time. This suggests that eGFRDiff could be used clinically as a laboratory-based screen to identify older adults in need for cognitive assessment.

Examining the Combined Estimated Effects of Hearing Impairment and Depression on Cognitive Decline and Dementia

Late-life depression is a comorbidity which may co-occur in older adults with hearing loss- each as prevalent and independent modifiable risk factors for dementia. We used data from 1,820 participants (74 ± 2.8 years, 38% Black race) from the Health Aging and Body Composition Study to test if the hearing loss-dementia/cognitive decline (Modified Mini Mental State Exam[3MS] and Digit Symbol Substitution[DSST]) relationship differed in hearing impaired participants who also had depressive symptoms. Depressive symptoms were defined as CES-D 10 ≥10) at one or more visits from years 1-5. Algorithmic incident dementia defined using medication use, hospitalizations and cognitive test scores. Audiometric hearing loss was measured at year 5 and categorized as normal/mild vs ≥moderate loss. In linear mixed models adjusted for demographic and clinical covariates, presence of both hearing loss and depressive symptoms (vs. having neither) was associated with faster rates of decline in 3MS (-0.30, 95% CI:-0.78, -0.19) and DSST (-0.35,95% CI:-0.67, -0.03) over 10 years of follow-up. Both hearing loss and depressive symptoms (vs. neither) was associated with increased risk (hazard ratio (HR):2.91, 95%CI: 1.59, 5.33) of incident dementia in multivariable-adjusted Cox proportional hazards models. Comorbid conditions among hearing impaired older adults should be considered and may aid in dementia prevention and management strategies.

Motor and Basic Cognitive Functions in Children with Acute Lymphoblastic Leukemia Undergoing Induction or Consolidation Chemotherapy.

Children with acute leukemia (ALL) often suffer from several disease and treatment related side-effects during treatment. The aim of the present study was to determine the gross and fine motor functioning and basic cognitive performance of children (n = 25) with ALL who were undergoing induction or consolidation chemotherapy and to compare these characteristics to a normative group (n = 21) of age-matched typically developing children. We assessed the children's motor functions with the Bruininks-Oseretsky Test of Motor Proficiency Second Edition-Short Form and the Nine-hole Peg Test, and we used the Modified Mini-Mental State Exam (MMSE) to evaluate their cognitive performance. Compared to the normative group, children with ALL had lower scores on total motor proficiency and sub-tests scores of motor functions (p < .05), and on the Nine-hole Peg Test performance (p < .05); but their cognitive performance on the MMSE was not significantly different. Children with ALL would likely benefit from structured exercise and rehabilitative interventions during chemotherapy to prevent and/or ameliorate ALL-related motor dysfunction. We also suggest that their cognitive functioning should be further investigated with more extensive well-validated neurocognitive tests for children (e.g., the Wechsler intelligence scales).

Automated assessment of speech production and prediction of MCI in older adults

The population of older adults is growing dramatically and, with it comes increased prevalence of neurological disorders, including Alzheimer’s disease (AD). Though existing cognitive screening tests can aid early detection of cognitive decline, these methods are limited in their sensitivity and require trained administrators. The current study sought to determine whether it is possible to identify persons with mild cognitive impairment (MCI) using automated analysis of spontaneous speech. Participants completed a brief neuropsychological test battery and a spontaneous speech task. MCI was classified using established research criteria, and lexical-semantic features were calculated from spontaneous speech. Logistic regression analyses compared the predictive ability of a commonly-used cognitive screening instrument (the Modified Mini Mental Status Exam, 3MS) and speech indices for MCI classification. Testing against constant-only logistic regression models showed that both the 3MS [χ 2(1) = 6.18, p = .013; AIC = 41.46] and speech indices [χ 2(16) = 32.42, p = .009; AIC = 108.41] were able to predict MCI status. Follow-up testing revealed the full speech model better predicted MCI status than did 3MS (p = .049). In combination, the current findings suggest that spontaneous speech may have value as a potential screening measure for the identification of cognitive deficits, though confirmation is needed in larger, prospective studies.

The role of functional status on the relationship between blood pressure and cognitive decline: the Cardiovascular Health Study.

To examine whether self-reported functional status modified the association between blood pressure (BP) and cognitive decline among older adults. The study included 2097 US adults aged 75 years and older from the Cardiovascular Health Study, followed for up to 6 years. Functional status was ascertained by self-reported limitation in activities of daily living (ADL; none vs. any). Cognitive function was assessed by the Modified Mini Mental State Exam (3MSE). We used linear mixed models to examine whether the presence of at least one ADL limitation modified the association between BP and cognitive decline. Potential confounders included demographics, physiologic measures, antihypertensive medication use and apolipoprotein E ε4 allele. We conducted stratified analyses for significant interactions between BP and ADL. The association between BP and change in 3MSE differed by baseline ADL limitation. Among participants without ADL limitation, elevated systolic BP (≥140 mmHg) was associated with a 0.15 decrease (95% CI -0.24 to -0.07); P value for interaction less than 0.001, whereas in those with an ADL limitation, elevated systolic BP was independently associated with a 0.30 increase in 3MSE scores per year (95% CI 0.06-0.55). Elevated diastolic BP (≥80 mmHg) was associated with an increase in cognitive function in both groups, although the increase was greater in those with ADL limitation (0.47 points per year vs. 0.18 points per year, P value for interaction = 0.01). Elevated BP appears to be associated with a decrease in cognitive scores among functioning older adults, and modest improvements in cognitive function among poorly functioning elders.

Genotype, resilience and function and physical activity post hip fracture

BackgroundIndividuals who are resilient are more likely to engage in functional tasks and exercise post hip fracture. There may be a genetic predisposition to being resilient. ObjectivesThis study tested the direct and indirect association of 10 candidate genes, age, cognition, gender, comorbidities, pain and social activity on resilience, function and exercise post hip fracture. MethodThis was a descriptive study including 172 community dwelling older adults. Measures included: age, gender, cognition (Modified Mini Mental Status Exam), comorbidities, social activities (self-report), DNA (GRM1, NTRK1, NTRK2, GNB3, NPY, SLC6A15. SLC6A4, BDNF, CR1TR1, FKBP5), pain (areas of pain and Numeric Rating Scale), function (Physical and Instrumental Activities of Daily Living; Lower Extremity Gains Score; Short Physical Performance Battery; Grip Strength) and exercise (Yale Physical Activity Scale). ResultsThe majority of participants were Caucasian (93%), 50% were women and the average age was 81.09 (SD = 7.42). There were significant associations between resilience and single nucleotide polymorphisms from GRM1, NTRK1, NTRK2, GNB3, NPY and SLC6A15. Resilience, age, cognition, social activity, pain and genetic variability were directly and/or indirectly associated with exercise and/or function. DiscussionThis study highlights the importance of resilience for engagement in exercise and function after hip fracture and provides preliminary evidence for a genetic role for resilience.

A Pilot Randomized Controlled Trial Examining the Effects of Tai Chi and Electronic Tablet Use on Older Adults' Cognition and Health.

To evaluate the feasibility of Tai Chi (TC) and electronic tablet (ET) interventions on older adults' cognition and health and to explore participants' perceptions of intervention activities. An emergent embedded experimental mixed methods design was used in which the qualitative strand helped explain intervention results. Older adults who participate in TC classes will have improved cognition and health compared with older adults who participate in ET classes. Twenty-six participants from two assisted living residences were recruited and randomized to receive nine TC or ET classes. The Modified Mini Mental State Exam was used to measure cognition and the SF-12v2 assessed perceived health before and after the intervention. Participants were invited to share perceptions of the two interventions. Institutional review board approval was obtained and participants provided signed consent for both quantitative and qualitative strands. There was no significant difference within or between groups on cognition and health scores. TC and ET use are activities that can be delivered in the community and have the potential to promote compensatory scaffolding as described by the revised scaffolding theory of aging and cognition. Future research should involve larger samples and teaching methods that promote learning postures.

What is the prevalence of cognitive impairment in lupus and which instruments are used to measure it? A systematic review and meta-analysis.

To systematically review the literature on the prevalence of Cognitive Dysfunction (CD) in SLE patients in studies that used a specified neuropsychological instrument. This review was prepared with a protocol following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Protocols statement. Literature search in Ovid Medline, Embase, and Psyc INFO for articles on CD in adult SLE patients was conducted. Included studies were critically appraised (Newcastle-Ottawa Evaluation Scale) and the Pooled Prevalence (PP) of CD was studied for all instruments. The association between demographics and CD, the risk of CD in SLE compared to healthy subjects and patients with RA, and the course of CD over time were studied narratively whenever sufficient information was available. Of 8054 references, 670 were selected for detailed review and 78 were included in the final analysis. Comprehensive Battery (CB) was utilized in 35 studies in 2463 SLE patients and PP was 38% (95%; CI: 33-43%). The CD prevalence was higher in NPSLE [PP 39% (95% CI: 24-55%]. Automated Neuropsychological Assessment Metric (ANAM) was utilized in 7 studies in 438 patients (PP of CD 26% (95% CI: 12-42%). Other less frequently utilized tools were the Modified Mini-Mental State Exam (MMSE), Montreal Cognitive Assessment (MoCA), Controlled Oral Word Association Test (COWAT) and The Hopkins Verbal Learning Test-Revised (HVLT-R) and subjective tools and others. The relative risk for CD in SLE was greater when compared to RA and to healthy individuals; RR being 1.80 and 2.80, respectively. Information on demographics and its association with CD was very heterogeneous among studies. Patients with lupus have a high prevalence of CD. The delay in diagnosis of CD is complex; although caregivers and patients express concerns about cognitive function, testing for CD often imposes administrative and cost burdens. There is an unmet need to identify the best screening, diagnostic metrics of CD. The assessment of cognitive function over time, and the association of demographics with CD, will require further research.

APOEε4 and slow wave sleep in older adults.

Slow wave (or stage N3) sleep has been linked to a variety of cognitive processes. However, the role of stage N3 in the elderly is debated. The link between stage N3 and episodic memory may be weakened or changed in the older adult population, possibly due to several altered mechanisms impacting the cellular structure of the brain. The bases for the age-related dissociation between stage N3 and cognition are not understood. Since APOEε4 status is the strongest genetic risk factor for cognitive decline, we assessed whether the ε4 allele is associated with stage N3 sleep. Participants were from the population-based Osteoporotic Fractures in Men (MrOS) cohort with polysomnography and APOEε4 genotype data (n = 2,302, 100% male, mean age 76.6 years). Sleep stages were objectively measured using overnight in-home polysomnography and central electroencephalogram data were used to score stage N3 sleep. Cognitive function was assessed using the Modified Mini Mental State Exam (3MS). The APOE rs429358 single nucleotide polymorphism, which defines the APOEε4 allele, was genotyped using a custom genotyping array. Total time in stage N3 sleep was significantly higher (p<0.0001) among the 40 MrOS participants carrying two copies of the ε4 allele (62±5.2 minutes) compared with 43±1.5 minutes for carriers of one ε4 allele (n = 515) and 40±0.8 minutes for ε4 non-carriers (n = 1747). All results were independent of sleep efficiency, number of sleep cycles, and apnea hypopnea index. These findings support an association between APOEε4 genotype and sleep stage N3 in the elderly. Increased total stage N3 duration among ε4/ε4 carriers does not appear to reflect compensation for prior cognitive decline and may reflect overactive downscaling of synapses during sleep. If confirmed, these results might in part explain the high risk of age-related cognitive decline and AD among APOE ε4/ε4 carriers.

Dietary Sodium/Potassium Intake Does Not Affect Cognitive Function or Brain Imaging Indices

Background: Dietary sodium may influence cognitive function through its effects on cerebrovascular function and cerebral blood flow. Methods: The aim of this study was to evaluate the association of dietary sodium intake with cognitive decline in community-dwelling older adults. We also evaluated the associations of dietary potassium and sodium:potassium intake with cognitive decline, and associations of these nutrients with micro- and macro-structural brain magnetic resonance imaging (MRI) indices. In all, 1,194 participants in the Health Aging and Body Composition study with measurements of dietary sodium intake (food frequency questionnaire [FFQ]) and change in the modified Mini Mental State Exam (3MS) were included. Results: The age of participants was 74 ± 3 years with a mean dietary sodium intake of 2,677 ± 1,060 mg/day. During follow-up (6.9 ± 0.1 years), 340 (28%) had a clinically significant decline in 3MS score (≥1.5 SD of mean decline). After adjustment, dietary sodium intake was not associated with odds of cognitive decline (OR 0.96, 95% CI 0.50–1.84 per doubling of sodium). Similarly, potassium was not associated with cognitive decline; however, higher sodium:potassium intake was associated with increased odds of cognitive decline (OR 2.02 [95% CI 1.01–4.03] per unit increase). Neither sodium or potassium alone nor sodium:potassium were associated with micro- or macro-structural brain MRI indices. These results are limited by the use of FFQ. Conclusions: In community-dwelling older adults, higher sodium:potassium, but not sodium or potassium intake alone, was associated with decline in cognitive function, with no associations observed with micro- and macro-structural brain MRI indices. These findings do not support reduction dietary sodium/increased potassium intake to prevent cognitive decline with aging.

Intradialytic Cognitive and Exercise Training May Preserve Cognitive Function

IntroductionCognitive decline is common and increases mortality risk in hemodialysis patients. Intradialytic interventions like cognitive training (CT) and exercise training (ET) may preserve cognitive function.MethodsWe conducted a pilot randomized controlled trial of 20 hemodialysis patients to study the impact of 3 months of intradialytic CT (tablet-based brain games) (n = 7), ET (foot peddlers) (n = 6), or standard of care (SC) (n = 7) on cognitive function. Global cognitive function was measured by the Modified Mini Mental Status Exam (3MS), psychomotor speed was measured by Trail Making Tests A and B (TMTA and TMTB), and executive function was assessed by subtracting (TMTB − TMTA). Lower 3MS scores and slower TMTA and TMTB times reflected worse cognitive function. P values for differences were generated using analysis of variance, and 95% confidence intervals (CIs) and P values were generated from linear regression.ResultsPatients with SC experienced a decrease in psychomotor speed and executive function by 3 months (TMTA: 15 seconds; P = 0.055; TMTB: 47.4 seconds; P = 0.006; TMTB − TMTA; 31.7 seconds; P = 0.052); this decline was not seen among those with CT or ET (all P > 0.05). Compared with SC, the difference in the mean change in 3MS score was −3.29 points (95% CI: −11.70 to 5.12; P = 0.42) for CT and 4.48 points (95% CI: −4.27 to 13.22; P = 0.30) for ET. Compared with SC, the difference in mean change for TMTA was −15.13 seconds (95% CI: −37.64 to 7.39; P = 0.17) for CT and −17.48 seconds (95% CI: −41.18 to 6.22; P = 0.14) for ET, for TMTB, the difference was −46.72 seconds (95% CI: −91.12 to −2.31; P = 0.04) for CT and −56.21 seconds (95% CI: −105.86 to −6.56; P = 0.03) for ET, and for TMTB – TMTA, the difference was −30.88 seconds (95% CI: −76.05 to 14.28; P = 0.16) for CT and −34.93 seconds (95% CI: −85.43 to 15.56; P = 0.16) for ET.ConclusionPreliminary findings of our pilot study suggested that cognitive decline in psychomotor speed and executive function is possibly prevented by intradialytic CT and ET. These preliminary pilot findings should be replicated.

Geriatric Assessment Metrics Are Associated with Hospital Length of Stay in Pre-Bone Marrow Transplant Myeloma Patients

A geriatric assessment (GA) is a global approach to improve healthy aging, wherein occult problems are assessed and intervened upon using a multidisciplinary method. A GA is feasible and can predict chemotherapy-induced toxicity and overall survival in cancer patients. Biomarkers of aging are also being explored as objective and reproducible measures of health and fitness. p16INK4a (p16) is a marker of cellular senescence that rises exponentially with chronologic age and is influenced by factors such as physical activity, smoking, and solid tumor chemotherapy. Here, we investigated the relationship of both the GA and molecular (i.e. p16) metrics in pre-bone marrow transplant (BMT) multiple myeloma (MM) patients. We selected this group for our studies as BMT patients are a vulnerable cohort in which transplant eligibility is subjective and age related. BMT patients are also at high risk for adverse events and treatment toxicity. In this preliminary analysis, we explored the predictive value of GA metrics and p16 with inpatient length of stay (LOS) during autologous BMT.Methods: We performed a pilot prospective cohort study on 55 MM patients during their pre-transplant evaluation. MM patients >18 years completed GA assessments related to physical function, distress, comorbidities, social support, and cognition. Patients completed surveys using the Brief Fatigue Inventory (BFI) (scale 1-10; moderate fatigue 4-6, severe fatigue 7+); Hospital Anxiety and Depression (HADS) (borderline case 8-10, definite case 11+); medical outcome study-social support survey (MOS-SSS) (scale 0-100, higher scores indicated greater support), Human Activity Profile (HAP) maximum activity score (MAS) and HAP-adjusted activity score (AAS), a 94-item questionnaire ranking tasks according to energy use validated in the BMT population, with higher scores indicating higher activity (Herzberg BBMT 2010). Objective measures of physical activity were measured using the Short Physical Performance Battery (SPPB) (range 0-12; impairment <9) and cognition was evaluated using the Modified Mini Mental Status exam (3MS). At the pre-transplant evaluation, p16 mRNA was measured in peripheral blood T-cells using established laboratory techniques (Liu Aging Cell 2009). The association between GA metrics and p16 were evaluated using Spearman's correlation coefficient. Univariable generalized linear models were fit to model LOS as a function of GA metrics or p16.Results: The median patient age was 61 (range 42-76). Most patients exhibited early stage disease (ISS Stage 1 53%) with minimal comorbidities (HCT-CI median 1; range 0-8) and a median of 2 prior lines of treatment (range 1-11). Pre-transplant Karnofsky Performance Status (KPS) was reported as 70% (n=10), 80% (n=10), 90% (n=15) and 100% (n=12). 7 patients did not proceed with BMT, 1 inpatient for BMT. Patients reported moderate fatigue by BFI (median 4.3; range 0-9.8), with minimal anxiety or depression as measured by the HADS. Self-reported physical activity by HAP-MAS was 73 (range 30-94) and HAP-AAS was 64 (range 20-94). Patients reported high levels of social support (median 86.7%; range 18.2-100) by MOS-SSS. Objective measures of physical function were also high as measured by the SPPB (median 10; range 4-12) and no cognitive impairment was identified by the 3MS. p16 expression was adjusted for age and did not correlate with GA tools including BFI, HADS, HAP-AAS, HAP-MAS, MOS-SSS, SPPB or 3MS. The median length LOS during transplant was 16 days (range 12-36). Univariate analysis revealed that SPPB score was significantly associated with LOS, where each one unit increase in physical performance corresponded to an average LOS decrease of 0.63 days (p=0.04). Self-reported activity by HAP-AAS also correlated with LOS (p=0.05). LOS was not influenced by p16, age, KPS or HCT-CI. Age and HCT-CI had no relationship with SPPB scores, but KPS did (p=0.03727).Conclusions: A comprehensive GA can be used to identify factors that contribute to BMT outcomes. Physical function appears to be most predictive of hospital LOS as measured by SPPB or a detailed self-report of physical function. Baseline p16 levels had no relationship with GA metrics in this selected population. A standardized approach for determining patient fitness including SPPB and HAP-AAS assessments may improve treatment tolerance, reduce hospital LOS, and decrease the risk for adverse outcomes in BMT populations. DisclosuresJaglowski:Immunomedics: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Seattle Genetics: Consultancy.

Higher serum insulin-like growth factor-1 is associated with better cognitive performance in persons with mild cognitive impairment.

Serum insulin-like growth factor-1 (IGF-1) is a mitogenic peptide involved in the regulation of cell proliferation, differentiation, and apoptosis in a wide variety of cells and tissues. Recent research suggests higher circulating levels of IGF-1 are associated with better cognitive performance in healthy older adults and in early stages of Alzheimer's disease, although the cognitive profile associated with elevated IGF-1 has not been examined in persons with mild cognitive impairment. Thirty-one participants (age: 83.71 ± 3.59 years; 58% women) with mild cognitive impairment completed neuropsychological testing and 12-hour fasting blood draw to assess serum IGF-1. Partial correlations between serum IGF-1 and neuropsychological measures were conducted, adjusting for insulin, body mass index, and age. Higher IGF-1-values were associated with better global cognition (Modified Mini Mental State Exam: r = 0.39, P = 0.04) and verbal list learning (Hopkins Verbal Learning Test learning: r = 0.38, P = 0.05), Hopkins Verbal Learning Test free recall (r = 0.41, P = 0.03), and Hopkins Verbal Learning Test recognition discriminability (r = 0.46, P = 0.01). A similar trend emerged for executive function as tested by the Frontal Assessment Battery (r = 0.33, P = 0.09). Results suggest higher levels of serum IGF-1 are associated with better cognitive performance in persons with mild cognitive impairment, particularly on tests of learning and memory. These findings suggest IGF-1 may be neuroprotective not only in healthy older adults, but also in adults in the earliest stages of Alzheimer's disease. Further investigation is needed to clarify the nature of this relationship, particularly prospective studies.

Educational Attainment, MRI Changes, and Cognitive Function in Older Postmenopausal Women from the Women's Health Initiative Memory Study

The relationship between neuropathology and clinically manifested functional and cognitive deficits is complex. Clinical observations of individuals with greater neuropathology who function better than some individuals with less neuropathology are common and puzzling. Educational attainment, a proxy for "cognitive reserve," may help to explain this apparent contradiction. The objective of this study is to determine if educational attainment is correlated with cognitive decline, brain lesion volume, and total brain atrophy. One thousand three hundred ninety of the 7,479 community-dwelling women 65 years of age and older enrolled in the Women's Health Initiative Memory Study, two parallel randomized, placebo-controlled clinical trials comparing unopposed and opposed postmenopausal hormone therapy with placebo, were studied. Study participants received annual assessments of global cognitive function with the Modified Mini Mental State exam. One thousand sixty-three participants also received supplemental neurocognitive battery and neuroimaging studies. Magnetic resonance imaging was used to calculate total ischemic lesion and brain volumes. Incident cases of probable dementia and mild cognitive impairment were centrally adjudicated. After adjustment for total lesion and total brain volumes (atrophy), higher educational attainment predicted better cognitive performance (p < 0.001). Following conversion to dementia/MCI, higher education predicted steeper declines in cognitive function (p < 0.001). Thus, higher educational attainment was associated with a delay in diagnosis of dementia/MCI in the face of a growing neuropathological load.

Circadian activity rhythm patterns in nondemented older women and cognitive function 5 years later

Patients with dementia often have impaired sleep wake cycles and circadian rhythms but the direction of this association is less clear. Weaker circadian activity rhythm (CAR) patterns are associated with health declines and could predict cognitive impairment. The object of this study was to determine whether CAR patterns were associated with cognitive tasks 5 years later. We studied 1,298 community dwelling older women (age = 82.8 ± 3 years), as part of an ongoing prospective study. Women with dementia at initial assessment were excluded. CAR measures were obtained from actigraphy and analyzed as phase of peak activity (acrophase) and quartile of amplitude (peak-to-nadir difference), mesor and robustness of rhythm. Cognitive performance was assessed using Modified Mini Mental Status Exam (3MS), California Verbal Learning Task (CVLT-II) 10-minute delayed recall, backward digit span, Trails B, categorical fluency and verbal fluency 5 years later. We used ANCOVA to determine differences in cognitive performance between the highest and lowest category of each predictor. Analyses were adjusted for age, education, body mass index, caffeine use, physical activity, depression, antidepressant or benzodiazepine use, and comorbidities. Overall, weaker CAR patterns were associated with poorer performance on measures of executive function (Trails B and categorical fluency) but not on other cognitive domains. Specifically, women with lower amplitude performed worse on both Trails B and categorical fluency (p<0.05); those with lower mesor or weaker robustness had worse categorical fluency (p≤0.05) and participants with delayed acrophase had worse performance on Trails B (p<0.05) and a trend towards worse scores on categorical fluency and 3MS (p=0.06 for both). In summary, circadian measures were related to executive function tasks involving processing speed, along with either task switching or the lexical axis. CAR patterns in older non-demented women are associated with worse executive function (but not performance on other cognitive tasks) 5 years later. Etiology of this requires further study and may involve underlying vascular disease.

Reduced heart rate variability is associated with worse cognitive function in elderly Mexican-Americans

Heart rate variability (HRV) is a subclinical measure of central autonomic function. Reduced HRV has been found to be a strong predictor of cardiovascular risk factors, cardiovascular events and mortality. Therefore, reduced HRV may be associated with cognitive neurodegeneration. Yet this has been relatively unexplored, particularly in minority populations. We investigated whether autonomic nervous system dysfunction, measured as reduced heart rate variability, was associated with worse cognitive function in elderly Mexican Americans. The Sacramento Area Latino Study on Aging (SALSA) is a prospective cohort study of 1,789 community-dwelling Mexican-Americans aged 60–101 years at baseline in 1998–1999. SALSA includes seven annual study visits. HRV was measured in a total of 869 subjects who participated in either visit 5 or 6 and thus constituted our analytical sample. HRV was assessed using the ANS2000 which is an ECG monitor and respiration pacer measuring variability in heart rate in response to deep breathing. Cognitive function was assessed using the Modified Mini Mental State Exam (3MS), a 100-point test of global cognitive function. For ease of interpretation, we categorized HRV into quartiles (Q1 to Q4: reduced to high HRV). We fit linear regression models to estimate the associations between quartile of HRV and cognitive function (3MS). Our sample of 869 participants had a mean age of 75 years (SD=6.1) and included 59% females. A total of 14% of the participants reported having had a stroke, 41% had type-2 diabetes, and more than 90% had hypertension. Reduced HRV was associated with older age, lower education, having had a stroke, a diagnosis of type-2 diabetes, hypertension, and elevated depressive symptoms. In models adjusted for age, gender, education, diabetes, stroke, and depressive symptoms, compared to subjects in the highest quartile of HRV, those in quartile 1 had a 4-point lower mean 3MS score (p<0.01), those in quartile 2 had a 2-point lower mean 3MS score (p=0.04), and those in quartile 3 had a 1-point lower mean 3MS score (p=0.35). Reduced HRV is associated with worse performance on the test of global cognitive function, above and beyond traditional cardiovascular risk factors.

Use of Days of the Week in a Modified Mini-Mental State Exam (M-MMSE) for Detecting Geriatric Cognitive Impairment

The purpose of this study was to compare a modified version of the Mini-Mental State Examination (MMSE) with the standard MMSE and the Mini-Cog in patients ≥65 years old, stratified by education and literacy level. This cross-sectional exploratory study enrolled a convenience sample of 219 patients with a complaint of memory loss or a diagnosis of dementia from a geriatric outpatient clinic, nursing home, senior center, and university hospital. The MMSE was administered, and in addition to spelling and serial 7s backward, patients were asked to recite the days of the week backward with the intent to reduce educational bias. Scores on the modified MMSE were compared with scores of the MMSE and the Mini-Cog. Of the 219 patients, 157 were identified with cognitive impairment by the Mini-Cog. Using a cutoff of ≤23, the MMSE identified 118 patients and the modified MMSE identified 91 patients with cognitive impairment, and with a cutoff of ≤27 the MMSE identified 168 and the modified MMSE 149 patients. All cognitively intact subjects correctly recited the days of the week backward. Specificity of the modified MMSE was higher than the MMSE for most groups. The highest sensitivity and specificity (94% and 88%, respectively) as well as positive and negative predictive values (96% and 81%, respectively) were in patients with low levels of education for the modified MMSE using a cut off of ≤27. Using the days of the week in the MMSE among illiterate and semiliterate participants and with education less than high school, and using a cutoff of 27 of 30, correlates better with Mini-Cog for dementia screening, with fewer false positives.

Do changes in circulating biomarkers track with each other and with functional changes in older adults?

It is unclear if changes in proposed circulating biomarkers of aging are strongly correlated to each other or functional change. We tested if biomarker changes track with each other and with functional measures over 9 years in older adults. Dehydroepiandrosterone sulfate (DHEAS), adiponectin, insulin-like growth factor 1 (IGF-1), IGF binding proteins 1 (IGFBP-1) and 3 (IGFBP-3), interleukin-6 (IL-6), cholesterol, and function (gait speed, grip strength, Modified Mini Mental Status Exam [3MSE] and Digit Symbol Substitution Test [DSST] scores) were measured in 1996-1997 and 2005-2006 in the Cardiovascular Health Study All Stars study (N = 901, mean [standard deviation, SD] age 85.3 [3.6] years in 2005-2006). Adjusted Pearson correlations illustrated if biomarkers tracked together. Multivariable linear regression demonstrated if biomarker changes tracked with functional changes. Correlations among biomarker changes were mostly <0.2. In models with each biomarker entered separately, a 1-SD increase biomarker change was associated with change in function as follows: grip strength (DHEAS β = 0.61kg, p = .001; IL-6 β = -0.46kg, p = .012; cholesterol men β = 0.79kg, p = .016); gait speed (DHEAS β = 0.02 meters per second, p = .039; IL-6 β = -0.018 meters per second, p = .049); and DSST score (DHEAS women β = 1.46, p = .004; IL-6 β = -0.83, p = .027). When biomarkers were entered in the same model, significant associations remaining were as follows: grip strength (DHEAS β = 0.54kg, p = .005; IL-6 β = -0.43kg, p = .022); 3MSE score (IGF-1 β = 0.96, p = .04; IGFBP-3 β = -1.07, p = .024); and DSST score (DHEAS women β = 1.27, p = .012; IL-6 β = -0.80, p = .04). Changes in biomarkers were poorly correlated, supporting a model of stochastic, independent change across systems. DHEAS and IL-6 tracked most closely with function, illustrating that changes in inflammation and sex steroids may play dominant roles in changes of these functional outcomes.

Cardiovascular Risk Score, Cognitive Decline, and Dementia in Older Mexican Americans: The Role of Sex and Education

BackgroundThe purpose of this study was to examine the associations of cardiovascular disease (CVD) risk with cognitive decline and incidence of dementia and cognitive impairment but not dementia (CIND) and the role of education as a modifier of these effects.Methods and ResultsOne thousand one hundred sixteen Mexican American elderly were followed annually in the Sacramento Area Latino Study on Aging. Our sex‐specific 10‐year CVD risk score included baseline age, systolic blood pressure, total cholesterol, high‐density lipoprotein, smoking, body mass index, and diabetes. From adjusted linear mixed models, errors on the Modified Mini–Mental State Exam (3MSE) were annually 0.41% lower for women at the 25th percentile of CVD risk, 0.11% higher at the 50th percentile, and 0.83% higher at the 75th percentile (P value of CVDrisk×time <0.01). In men, 3MSE errors were annually 1.76% lower at the 25th percentile of CVD risk, 0.96% lower at the 50th percentile, and 0.12% higher at the 75th percentile (P value of CVDrisk×time <0.01). From adjusted linear mixed models, the annual decrease in the Spanish and English Verbal Learning Test score was 0.09 points for women at the 25th percentile of CVD risk, 0.10 points at the 50th percentile, and 0.12 points at the 75th percentile (P value of CVDrisk×time=0.02). From adjusted Cox models in women, compared with having <6 years of education, having 12+ years of education was associated with a 76% lower hazard of dementia/CIND (95% CI, 0.08 to 0.71) at the 25th percentile of CVD risk and with a 45% lower hazard (95% CI, 0.28 to 1.07) at the 75th percentile (P value of CVDrisk×education=0.05).ConclusionsCVD risk score may provide a useful tool for identifying individuals at risk for cognitive decline and dementia.

Magnitude and consequences of misclassification of incident hip fractures in large cohort studies: the Study of Osteoporotic Fractures and Medicare claims data

In the Study of Osteoporotic Fractures (SOF), 18.5 % of incident hip fractures identified in Medicare Fee-for-Service claims data were not reported to or confirmed by the cohort. Cognitive impairment was a modest risk factor for false-negative hip fracture ascertainment via self-report. Prospective cohort studies of fractures that rely on participant self-report to be the initial signal of an incident fracture could be prone to bias if a significant proportion of fractures are not self-reported. We used data from the SOF merged with Medicare Fee-for-Service claims data to estimate the proportion of participants who had an incident hip fracture identified in Medicare claims that was either not self-reported or confirmed (by review of radiographic reports) in SOF. Between 1/1/1991 and 12/31/2007, 647 SOF participants had a hip fracture identified in Medicare claims, but 120 (18.5 %) were either not reported to or confirmed by the cohort. False-negative hip fracture ascertainment was associated with a reduced modified Mini-Mental State Exam (MMSE) score (odds ratio 1.31 per SD decrease, 95 % C.I. 1.06-1.63). Point estimates of associations of predictors of incident hip fracture were changed minimally when the misclassification of incident hip fracture status was corrected with use of claims data. A substantial minority of incident hip fractures were not reported to or confirmed in the SOF. Cognitive impairment was modestly associated with false-negative hip fracture ascertainment. While there was no evidence to suggest that misclassification of incident hip fracture status resulted in biased associations of potential predictors with hip fracture in this study, false-negative incident fracture ascertainment in smaller cohort studies with limited power may increase the risk of type 2 error (not finding significant associations of predictors with incident fractures).