Brief cognitive assessment in a UK population sample -- distributional properties and the relationship between the MMSE and an extended mental state examination.

BACKGROUND: Despite the MMSE's known flaws, it is still used extensively as both a screening instrument for dementia and a population measure of cognitive ability. The aim of this paper is to provide data on the distribution of MMSE scores in a representative sample from the UK population and to compare it with an extended cognitive assessment (EMSE) which covers a wider range of cognitive domains and provides a wider range of difficulty levels. METHODS: The MMSE and the EMSE were administered to over 12,000 participants at the screening stage of the MRC Cognitive Function and Ageing Study (MRC CFAS). MRC CFAS is a multi-centre population-based study in England and Wales with respondents aged 65 years and older. RESULTS: Normative values on the MMSE and EMSE are presented by age group, sex and level of education. There are very large differences between age groups, with smaller differences seen between the sexes and by level of education. The EMSE extends the scores at the high end of the ability range, but is no better than the MMSE at differentiating between dementia and non-dementia. CONCLUSION: Population-derived norms are valuable for comparing an individual's score to the score that would be expected among the general population, given the individual's specific demographic characteristics.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

An investigation of whether factors associated with short-term attrition change or persist over ten years: data from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).

BACKGROUND: Factors associated with the loss of participants in long-term longitudinal studies of ageing, due to refusal or moves, have been discussed less than those with short term follow-up. METHODS: In a population-based study of cognition and ageing (the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS)), factors associated with dropout due to refusal and moving in the first follow-up period (over two years) are compared with factors associated with dropout over ten years. Participants at 10-year follow-up are compared with their age-standardised baseline contemporaries. RESULTS: Some consistent trends are found over the longer term. Refusers tended to have poorer cognition, less years of education, not have a family history of dementia and be women. Characteristics of people who moved differed between waves, but the oldest and people in worse health moved more. When surviving and responding individuals at ten years are compared with those of the same age at baseline many differences are found. Individuals of lower social class, education, cognitive ability, in residential care, with sight/hearing problems and poor/fair self-reported health are less likely to be seen after 10 years of follow-up. Individuals report more health problems when they participate in multiple interviews. CONCLUSION: The characteristics of refusers in the longer term are similar to those refusing to participate over the shorter term. Long-term follow-up studies will under represent the disadvantaged and disabled but represent full health status of participating individuals better. There are advantages and disadvantages to both short-term and long-term follow-up.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Examining the influence of gender, education, social class and birth cohort on MMSE tracking over time: a population-based prospective cohort study.

BACKGROUND: Whilst many studies have analysed predictors of longitudinal cognitive decline, few have described their impact on population distributions of cognition by age cohort. The aim of this paper was to examine whether gender, education, social class and birth cohort affect how mean population cognition changes with age. METHODS: The Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) is a multi-centre population based longitudinal study of 13,004 individuals in England and Wales. Using ten years of follow-up data, mean Mini-mental State Examination (MMSE) scores were modelled by age and birth cohort adjusting for non-random drop-out. The model included terms to estimate cohort effects. Results are presented for five year age bands between 65-95 years. RESULTS: At a population level, women show greater change in MMSE scores with age than men. Populations with lower education level and manual work also show similar effects. More recent birth cohorts have slightly higher scores. CONCLUSION: Longitudinal data can allow examination of population patterns by gender, educational level, social class and cohort. Each of these major socio-demographic factors shows some effect on whole population change in MMSE with age.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Pharmacological activation of the nuclear receptor REV-ERB reverses cognitive deficits and reduces amyloid-β burden in a mouse model of Alzheimer’s disease

Alzheimer’s disease currently lacks treatment options that effectively reverse the biological/anatomical pathology and cognitive deficits associated with the disease. Loss of function of the nuclear receptor REV-ERB is associated with reduced cognitive function in mouse models. The effect of enhanced REV-ERB activity on cognitive function has not been examined. In this study, we tested the hypothesis that enhanced REV-ERB function may enhance cognitive function in a model of Alzheimer’s disease. We utilized the REV-ERB agonist SR9009 to pharmacologically activate the activity of REV-ERB in the SAMP8 mouse model of Alzheimer’s disease. SR9009 reversed cognitive dysfunction of an aged SAMP8 mouse in several behavioral assays including novel object recognition, T-maze foot shock avoidance, and lever press operant conditioning task assessments. SR9009 treatment reduced amyloid-β 1–40 and 1–42 levels in the cortex, which is consistent with improved cognitive function. Furthermore, SR9009 treatment led to increased hippocampal PSD-95, cortical synaptophysin expression and the number of synapses suggesting improvement in synaptic function. We conclude that REV-ERB is a potential target for treatment of Alzheimer’s disease.</div

Dietary Patterns and Cognitive Function among Older Community-Dwelling Adults.

Diet may be an important modifiable risk factor for maintenance of cognitive health in later life. This study aimed at examining associations between common dietary indices and dietary patterns defined by factor analysis and cognitive function in older community-dwelling adults. Dietary information for 1499 participants from the Rancho Bernardo Study was collected in 1988⁻1992 and used to calculate the alternate Mediterranean diet score, Alternate Healthy Eating Index (AHEI)-2010 score and factor scores derived from factor analysis of nutrients. Global cognitive function, executive function, verbal fluency and episodic memory were assessed at approximate four-year intervals from 1988⁻2016. Linear mixed models were used to examine associations between dietary patterns and cognitive trajectories. Estimates for the highest vs. lowest tertile in models adjusting for age, sex, education, energy intake, lifestyle variables and retest effect showed greater adherence to the Mediterranean score was associated with better baseline global cognitive function (β (95% CI) = 0.33 (0.11, 0.55)). The AHEI-2010 score was not significantly associated with cognitive performance. Higher loading on a plant polyunsaturated fatty acid (PUFA)/vitamin E factor was associated with better baseline global cognitive function and executive function (β = 0.22 (0.02, 0.42) and β = -7.85 (-13.20, -2.47)). A sugar/low protein factor was associated with poorer baseline cognitive function across multiple domains. Dietary patterns were not associated with cognitive decline over time. Adherence to a healthy diet with foods high in PUFA and vitamin E and a low sugar to protein ratio, as typified by a Mediterranean diet, may be beneficial for cognitive health in late life

Enhancing Cognitive Function of Healthy Wistar Rats with Aqueous Extract of Centella Asiatica

Background: Centella asiatica (L.) Urb is a native herb from Asian countries such as India, China, and Indonesia. This herb has been widely used as a cure for various diseases. However, studies investigating the aqueous extract of Centella asiatica as a nootropic in healthy individuals are still very limited.Objective: This study aims to investigate the potential of aqueous extract of Centella asiatica in enhancing cognitive function of healthy male Wistar rats.Methods: Rats were randomly allocated to four treatment groups, i.e. without treatment and aqueous Centella asiatica extract at doses of 200, 400 and 800 mg/kg. To determine enhancement of cognitive function, novel object recognition (NOR) test was conducted after the course of treatment. Acetylcholine content was assessed by enzyme-linked immunosorbent assay.Results: There was a significantly high preference index towards the novel object in the NOR test in groups treated with 200 mg/kg and 800 mg/kg of the aqueous extract compared to control. This was further confirmed by a significant increase of brain acetylcholine content in rats treated with 200 mg/kg of the extract.Conclusion: Therefore, this study confirms that the aqueous extract is effective in enhancing cognitive performance of healthy Wistar rats

The reliability of assigning individuals to cognitive states using the Mini Mental-State Examination: a population-based prospective cohort study.

BACKGROUND: Previous investigations of test re-test reliability of the Mini-Mental State Examination (MMSE) have used correlations and statistics such as Cronbach's α to assess consistency. In practice, the MMSE is usually used to group individuals into cognitive states. The reliability of this grouping (state based approach) has not been fully explored. METHODS: MMSE data were collected on a subset of 2,275 older participants (≥ 65 years) from the population-based Medical Research Council Cognitive Function and Ageing Study. Two measurements taken approximately two months apart were used to investigate three state-based categorisations. Descriptive statistics were used to determine how many people remained in the same cognitive group or went up or down groups. Weighted logistic regression was used to identify predictive characteristics of those who moved group. RESULTS: The proportion of people who remained in the same MMSE group at screen and follow-up assessment ranged from 58% to 78%. The proportion of individuals who went up one or more groups was roughly equal to the proportion that went down one or more groups; most of the change occurred when measurements were close to the cut-points. There was no consistently significant predictor for changing cognitive group. CONCLUSION: A state-based approach to analysing the reliability of the MMSE provided similar results to correlation analyses. State-based models of cognitive change or individual trajectory models using raw scores need multiple waves to help overcome natural variation in MMSE scores and to help identify true cognitive change.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Who Lives Where and Does It Matter? Changes in the Health Profiles of Older People Living in Long Term Care and the Community over Two Decades in a High Income Country.

BACKGROUND: There have been fundamental shifts in the attitude towards, access to and nature of long term care in high income countries. The proportion and profile of the older population living in such settings varies according to social, cultural, and economic characteristics as well as governmental policies. Changes in the profiles of people in different settings are important for policy makers and care providers. Although details will differ, how change occurs across time is important to all, including lower and middle income countries developing policies themselves. Here change is examined across two decades in England. METHODS AND FINDINGS: Using the two Cognitive Function and Ageing Studies (CFAS I: 77% response, CFAS II: 56% response), two population based studies of older people carried out in the same areas conducted two decades apart, the study diagnosis of dementia using the Automated Geriatric Examination for Computer Assisted Taxonomy, health and wellbeing were examined, focusing on long term care. The proportion of individuals with three or more health conditions increased for everyone living in long term care between CFAS I (47.6%, 95% CI: 42.3-53.1) and CFAS II (62.7%, 95% CI: 54.8-70.0) and was consistently higher in those without dementia compared to those with dementia in both studies. Functional impairment measured by activities of daily living increased in assisted living facilities from 48% (95% CI: 44%-52%) to 67% (95% CI: 62%-71%). CONCLUSIONS: Health profiles of residents in long term care have changed dramatically over time. Dementia prevalence and reporting multiple health conditions have increased. Receiving care in the community puts pressure on unpaid carers and formal services; these results have implications for policies about supporting people at home as well as for service provision within long term care including quality of care, health management, cost, and the development of a skilled, caring, and informed workforce.CFAS II has been funded through a grant from the Medical Research Council (grant number G0601022). CFAS I was also funded through the Medical Research Council (grant number G9901400).This is the final version of the article. It first appeared from PLOS at http://dx.doi.org/10.1371/journal.pone.0161705

Residual negative symptoms differentiate cognitive performance in clinically stable patients with schizophrenia and bipolar disorder

Cognitive deficits in various domains have been shown in patients with bipolar disorder and schizophrenia. The purpose of the present study was to examine if residual psychopathology explained the difference in cognitive function between clinically stable patients with schizophrenia and bipolar disorder. We compared the performance on tests of attention, visual and verbal memory and executive function of 25 patients with schizophrenia in remission and 25 euthymic bipolar disorder patients with that of 25 healthy controls. Mediation analysis was used to see if residual psychopathology could explain the difference in cognitive function between the patient groups. Both patient groups performed significantly worse than healthy controls on most cognitive tests. Patients with bipolar disorder displayed cognitive deficits that were milder but qualitatively similar to those of patients with schizophrenia. Residual negative symptoms mediated the difference in performance on cognitive tests between the two groups. Neither residual general psychotic symptoms nor greater antipsychotic doses explained this relationship. The shared variance explained by the residual negative and cognitive deficits that the difference between patient groups may be explained by greater frontal cortical neurophysiological deficits in patients with schizophrenia, compared to bipolar disorder. Further longitudinal work may provide insight into pathophysiological mechanisms that underlie these deficits

Circadian rest-activity rhythms predict cognitive function in early Parkinson's disease independently of sleep

BACKGROUND: Cognitive impairment is a common and debilitating symptom of Parkinson's disease (PD), and its etiology is likely multifactorial. One candidate mechanism is circadian disruption. Although there is evidence of circadian abnormalities in PD, no studies have directly assessed their association with cognitive impairment. OBJECTIVES: Investigate whether circadian rest-activity rhythm is associated with cognitive function in PD independently of sleep. METHODS: Thirty-five participants with PD wore wrist actigraph monitors and completed sleep diaries for 7 to 10 days, then underwent neuropsychological testing. Rest-activity rhythm was characterized using nonparametric circadian rhythm analysis of actigraphy data. Objective sleep parameters were also estimated using actigraphy data. Hierarchical regression models assessed the independent contributions of sleep and rest-activity rhythm to cognitive performance. RESULTS: Less stable day-to-day rest-activity rhythm was associated with poorer executive, visuospatial, and psychomotor functioning, but not with memory. Hierarchical regressions showed that interdaily stability's contribution to cognitive performance was independent of sleep's contributions. Whereas sleep contributed to executive function, but not psychomotor or visuospatial performance, rest-activity rhythm stability significantly contributed to variance in all three of these domains, uniquely accounting for 14.4% to 17.6% of their performance variance. CONCLUSIONS: Our findings indicate that circadian rest-activity rhythm is associated with cognitive impairment independently of sleep. This suggests the possible utility of rest-activity rhythm as a biomarker for circadian function in PD. Future research should explore interventions to stabilize behavioral rhythms in order to strengthen circadian function, which, in turn, may reduce cognitive impairment in PD.R00 HL102241 - NHLBI NIH HHS; R01 AG048108 - NIA NIH HHSAccepted manuscrip