Longitudinal studies of aging often gather repeated observations of cognitive status to describe the development of dementia and to assess the influence of risk factors. Clinical progression to dementia is often conceptualized by a multistage model of several transitions that synthesizes time-varying effects. In this study, we assess the influence of risk factors on the transitions among three cognitive status: cognitive stability (normal cognition for age), memory impairment, and clinical dementia. We have developed a shared random effects model that not only links the propensity of transitions and to the probability of informative missingness due to death, but also incorporates heterogeneous transition between subjects. We evaluate four approaches using generalized logit and four using proportional odds models to the first order Markov transition probabilities as a function of covariates. Random effects were incorporated into these models to account for within-subject correlations. Data from the Einstein Aging Study are used to evaluate the goodness-of-fit of these models using the Akaike information criterion. The best fitting model for each type (generalized logit and proportional odds) is recommended and their results are discussed in more details.
Generalized Logit; Multi-Stage; Proportional Odds; Random Effects; Transition
A major challenge to developing primary preventive interventions for frailty and disability in older adults is lack of validated simple clinical tools to identify high-risk individuals without overt signs of poor health.
To examine the validity of the Walking While Talking test (WWT), a mobility stress test, to predict frailty, disability and death in high functioning older adults.
prospective cohort study.
631 community-residing adults age 70 and older participating in the Einstein Aging Study (mean follow-up 32 months). High functioning status at baseline was defined as absence of disability, dementia, and normal walking speeds.
Main outcome measures
Hazard ratios for frailty, disability, and all-cause mortality. Frailty was defined as presence of three out of the following five attributes: weight loss, weakness, exhaustion, low physical activity and slow gait. We also compared predictive validity of WWT with Short Physical Performance Battery (SPPB) for study outcomes.
218 subjects developed frailty, 88 disability, and 49 died. Each 10 cm/s decrease in WWT speed was associated with increased risk of frailty (Hazard ratio 1.12, 95% CI 1.06 to 1.18), disability (Hazard ratio 1.13, 95% CI 1.03 −1.23), and mortality (Hazard ratio 1.13, 95% CI 1.01 – 1.27). Most associations remained robust even after accounting for potential confounders and gait speed. Comparisons of HR and model fit suggest that WWT may better predict frailty whereas SPPB may better predict disability.
Mobility stress tests such as the WWT are robust predictors of risk of frailty, disability, and mortality in high functioning older adults.
Mobility; Frailty; Disability; Mortality; Gait
Patients who use an emergency department (ED) for acute migraine headaches have higher migraine disability scores and lower socioeconomic status and are unlikely to have used a migraine-specific medication prior to presentation to the ED. The objective was to determine if a comprehensive migraine intervention, delivered just prior to ED discharge, could improve migraine impact scores 1 month after the ED visit.
This was a randomized controlled trial of a comprehensive migraine intervention versus typical care among patients who presented to an ED for management of acute migraine. At the time of discharge, for patients randomized to comprehensive care, the authors’ protocol reinforced their diagnosis, shared a migraine education presentation from the National Library of Medicine, provided them with six tablets of sumatriptan 100 mg and 14 tablets of naproxen 500 mg, and if they wished, provided them with an expedited free appointment to our institution's headache clinic. Patients randomized to typical care received the care their attending emergency physicians (EPs) felt was appropriate. The primary outcome was a between-group comparison of the Headache Impact Test (HIT-6) score, a validated headache assessment instrument, 1 month after ED discharge. Secondary outcomes included an assessment of satisfaction with headache care and frequency of use of migraine-specific medication within that 1-month period.
Over a 19-month period, 50 migraine patients were enrolled. One-month follow-up was successfully obtained in 92% of patients. Baseline characteristics were comparable. One-month HIT-6 scores in the two groups were nearly identical (59 vs. 56, 95% confidence interval [CI] for difference of 3 = –5 to 11), as was dissatisfaction with overall headache care (17% vs. 18%, 95% CI for difference of 1% = –22% to 24%). Patients randomized to the comprehensive intervention were more likely to be using triptans or migraine-specific therapy (43% vs. 0%, 95% CI for difference of 43% = 20 to 63%) 1 month later.
A comprehensive migraine intervention, when compared to typical care, did not improve HIT-6 scores (a validated measure of the effect of migraine on one's daily life) 1 month after ED discharge. Future work is needed to define a migraine intervention that is practical and useful in an ED, where many underserved patients, of necessity, present for care.
Objective: to determine the association of high sensitivity C-reactive protein (HsCRP) levels with a risk of mobility disability and decline in older adults with and without vascular disease.
Design: prospective cohort.
Setting: community-residing population.
Subjects: six hundred and twenty-four adults age 70 and older (62% women) with gait and HsCRP assessments.
Main outcome measures: incident mobility disability (velocity <70 cm/s) and annual rates of decline on gait velocity.
Results: elevated HsCRP levels (≥3 mg/l) at baseline present in 224 of the 624 eligible subjects was associated with a faster annual decline in gait velocity of 0.91 cm/s (P = 0.02). Subjects with elevated HsCRP levels had increased risk of mobility disability (hazard ratio: 1.85, 95% CI: 1.09–3.14). Each one-unit increase in log HsCRP levels in the 406 subjects without prevalent mobility disability was associated with increased risk of mobility disability (hazard ratio: 1.33, 95% CI: 1.05–1.68). The association of baseline HsCRP levels with mobility disability and decline was stronger in the 224 individuals without vascular disease. The associations were not significant in the 400 subjects with vascular disease.
Conclusions: HsCRP levels predict mobility disability and accelerated decline in walking speed in older adults. These associations were stronger in those without vascular disease.
cohort study; epidemiology; gait; inflammation elderly
To assess the cross-sectional relationship of glycemic control to memory impairment and executive dysfunction in older adults with diabetes treated at an urban primary care center.
Participants and Methods
As part of a primary care-based cognitive screening program, we identified adults age 65 or older with a diagnosis of diabetes. Glycosylated hemoglobin level (HbA1c) was used to define diabetes as controlled (HbA1c <7) or inadequately controlled(HbA1c ≥ 7). Episodic memory was measured by quartile of free recall scores on the Free and Cued Selective Reminding Test. Executive function was measured using an ordinal composite score derived from animal fluency and months backward. These were the main predictors of diabetic control.
The 169 participants with diabetes had a median age of 74. The sample was 38% African American and 42% Latino. One hundred four (61%) had inadequately controlled diabetes. Memory impairment and executive dysfunction were independent predictors of diabetic control after adjusting for age and education. Binary logistic regression models indicated that the odds of inadequately controlled diabetes was higher for patients in the worst quartile of memory functioning compared to patients in higher quartiles of memory functioning (odds ratio = 6.4; 95% confidence interval: 2.3, 17.6). Any level of executive dysfunction increased the odds of inadequately controlled diabetes compared to patients in the best quintile of executive functioning (odds ratio =3.6; 95% confidence interval: 1.58, 8.35).
Memory impairment and executive dysfunction were associated with inadequately controlled diabetes. Though causal inferences are not robust in a cross-sectional study, we suggest that cognitive dysfunction may interfere with diabetes management and that inadequate diabetic control may contribute to cognitive dysfunction.
diabetes; dementia; cognitive impairment; African American; Latino
To determine whether dementia status and medical burden were independent predictors of emergency department (ED) visits and hospitalizations in older patients from an urban geriatric practice participating in a primary care based cognitive screening program.
Participants and Methods
A comprehensive chart review was conducted for 300 African American and Caucasian patients, including 46 with prevalent dementia and 28 with incident dementia using the Cumulative Illness Burden Scale. Hospital-based claims data was used to retrieve ED visits and hospital admissions for 5 years following baseline assessment.
Patients with dementia had a 49% higher rate of ED visits (IRR = 1.49; 95% CI = 1.06, 2.09) and an 83% higher risk of death than patients without dementia (HR = 1.83; 95% CI = 3.07, 0.03). Dementia status predicted hospital admissions after adjustment for medical burden (IRR = 1.37; 95% CI = 0.99, 1.89). For each one point increase in medical burden, there was an 11% increase in ED visits (IRR = 1.11; 95% CI = 1.06, 1.16), a 13% increase in hospital admissions (IRR = 1.13; 95% CI = 1.09, 1.17), and an 11% higher risk of death (HR = 1.11; 95% CI = 1.04, 1.17). Age did not predict utilization.
Dementia status and medical burden were independent predictors of ED visits and death in patients with clinically diagnosed dementia followed from the early stage of disease.
acute care utilization; dementia; primary care; hospitalizations; emergency department visits
This study examined the relationship between cognitive function and sleep onset/maintenance difficulties (SO/MD) in nondemented older adults. We hypothesized that SO/MD negatively impacts cognition and that older adults with lower education would be especially vulnerable to its effects.
The sample comprised 549 older adults from the Einstein Aging Study (EAS), a community-based sample. Participants completed neuropsychological assessment and a sleep questionnaire. Univariate ANCOVAs were performed with cognitive performance as a dependent variable, SO/MD (present or absent) and education (lower:≤12 years; higher:>12 years) as between-subjects factors, and age, ethnicity, gender, depression, and cardiovascular comorbidies as covariates.
Participants were an average age of 79.7±5.0 years (range=71–97). Fifty-seven percent (n=314) of the sample met criteria for SO/MD. Among participants with SO/MD, those with lower education performed more poorly on a test of category fluency than participants with higher education (means: 35.2 vs. 41.0, p<0.001); among older adults without SO/MD, educational attainment had no measurable effect on cognition (SO/MD × education interaction (F(1,536)=14.5, p=0.00)).
Consistent with the cognitive reserve hypothesis, older adults with lower education appear selectively vulnerable to the negative effects of sleep onset/maintenance difficulties on tests of verbal fluency.
Sleep; Neuropsychology; Cognitive Reserve; Elderly; Education; Depression
Individuals with amnestic mild cognitive impairment (aMCI) show deficits on traditional episodic memory tasks and reductions in speed of performance on reaction time tasks. We present results on a novel task, the Cued-Recall Retrieval Speed Test (CRRST), designed to simultaneously measure level and speed of retrieval. 390 older adults (mean age of 80.2 years), learned 16 words based on corresponding categorical cues. In the retrieval phase, we measured accuracy (% correct) and retrieval speed/reaction time (RT; time from cue presentation to voice onset of a correct response) across 6 trials. Compared to healthy elderly adults (HEA, n = 303), those with aMCI (n = 87) exhibited poorer performance in retrieval speed (difference = −0.13, p<.0001) and accuracy on the first trial (difference = −0.19, p<.0001), and their rate of improvement in retrieval speed was slower over subsequent trials. Those with aMCI also had greater within-person variability in processing speed (variance ratio = 1.22, p = 0.0098) and greater between-person variability in accuracy (variance ratio = 2.08, p = 0.0001) relative to HEA. Results are discussed in relation to the possibility that computer-based measures of cued-learning and processing speed variability may facilitate early detection of dementia in at-risk older adults.
Retrieval speed; intraindividual variability; variability; amnestic mild cognitive impairment; cued-recall task; neuropsychological assessment
Despite the strong need for evidence-based diagnostics, there is disagreement about the cognitive tools that best predict incident Alzheimer's disease (AD) in nondemented elders. We investigated the independent and combined contributions to the risk of AD of three key domains of cognitive assessment: neuropsychological measurement, self reports, and informant reports.
Longitudinal, community-based sample.
Einstein Aging Study.
Six hundred twenty-seven non-demented older adults aged 70 and above systematically recruited from the Bronx, NY.
Comprehensive assessment included neurological exam, behavioral questions, and neuropsychological testing. AD diagnoses were based on DSM-IV criteria assigned at a multidisciplinary consensus case conference. The major statistical analyses utilized Cox proportional hazards models (with age as the time scale), adjusted for gender, education, and depressive symptoms.
Forty-eight participants developed incident AD during a median of 3.3 years of follow-up. Self and informant reports of cognitive status as well as baseline scores on tests of episodic memory and psychomotor speed predicted the onset of AD. In models examining all the variables simultaneously, however, only the episodic memory tests and informant reports were associated with risk of AD. A likelihood ratio test confirmed the incremental effect of informant reports in addition to the neuropsychological test scores (P=0.035).
Informant ratings improved the prediction of AD conversion above and beyond objective memory impairment in non-demented elders. Combining these cognitive measures may provide a useful, empirical method for identifying individuals at high risk for future AD.
Cognitive complaints; Subjective memory complaints; Informant reports; AD prediction; Neuropsychological tests
Gait Velocity (GV) is predictive of hospitalizations and mortality in the elderly. In the US, elderly African Americans have higher rates of physical disability compared to Caucasians. Few studies have investigated if there are racial differences in GV in the elderly.
We performed a cross sectional analysis to investigate racial differences in GV.
Participants were part of the Einstein Aging Study, a longitudinal study of community-residing elderly in the Bronx, NY. They were recruited using Medicare and voter registration records. Records of 213 participants were analyzed.
Demographics, medical history, the Geriatric Depression Scale, the Blessed Information Memory Concentration Test, and the Total Pain Index (TPI) were collected. GV was measured using the GAITrite® mat.
We included 157 Caucasians and 56 African Americans. Caucasians were older (median 79.9y v 75.5y, p<0.01), more educated (median 14y v 12y, p<0.01) and had lower BMIs (mean 26.9±4.3 v 28.9±6.4, p=0.03). African Americans had higher proportions of female participants (80.4% v 59.9%, p<0.01) and diabetes (28.6% v 13.4%, p=0.01). Neither group had significantly higher pain levels. African Americans had a significantly slower GV (mean 90.2±17.9 v 99.1±20.1 cm/sec, p<0.01). This difference persists despite adjusting for multiple covariates. A 7.79 cm /sec slower gait speed in African Americans versus Caucasians was not explained by differences in common factors known to influence gait.
Differences in GV persist between African Americans and Caucasians despite adjusting for many confounders. Increases of just 10cm/sec are associated with reduced mortality. Further studies are needed to evaluate if there are modifiable risk factors that potentially explain this difference and if an intervention could reduce the discrepancy between the groups.
gait velocity; health disparities; elderly; physical function
Cognitive reserve is invoked to explain the protective effects of education and cognitively-stimulating activities against all-cause dementia and Alzheimer’s disease (AD). For non-native English speakers (n-NES), speaking English may be a cognitive activity associated with lower dementia risk. We hypothesized that n-NES have lower risk of incident dementia/AD and that educational level might modify this relationship. Participants took part in the Einstein Aging Study (Bronx, NY), a longitudinal study of aging and dementia. All (n = 1779) spoke fluent English and self-reported birthplace and whether English was their first language. n-NES additionally reported mother tongue, age of English acquisition, and current percentile-use of a non-English language. Nested Cox proportional hazards models progressively adjusted for gender, race, education, and immigrant and marital status estimated hazard ratios (HR) for incident dementia/AD as a function of n-NES status. 390 (22%) participants were n-NES. 126 incident dementia cases occurred during 4174 person-years of follow-up (median 1.44; range 0–16); 101 individuals met criteria for probable/possible AD. There was no statistically-significant association between n-NES status and incident dementia in the fully-adjusted model (HR 1.26; 95% CI 0.76–2.09; p = 0.36). Results were similar for AD. Stratification of education into three groups revealed increased risk of dementia for n-NES with ≥16 years of education (HR 3.97; 95% CI 1.62–9.75; p = 0.003). We conclude that n-NES status does not appear to have an independent protective effect against incident dementia/AD, and that n-NES status may contribute to risk of dementia in an education-dependent manner.
Cohort studies; dementia; incidence; multilingualism
The current study examined the relationship between cognitive function and falls in elders who did not meet criteria for dementia or Mild Cognitive Impairment (n=172). To address limitations of previous research, associations between cognitive function and falls controlled for the confounding effects of gait measures and other risk factors. A neuropsychological test battery was submitted to factor analysis yielding three orthogonal factors (verbal IQ, Speed/Executive Attention, Memory). Single and recurrent falls within the last 12 months were evaluated. We hypothesized that Speed/Executive Attention would be associated with falls. Additionally, we assessed whether associations between different cognitive functions and falls varied depending on whether single or recurrent falls were examined. Multivariate logistic regressions showed that worse scores on Speed/Executive Attention were associated with increased single and recurrent falls. Worse scores on Verbal IQ were related only to increased recurrent falls. Memory was not associated with either single or recurrent falls. These findings are relevant to risk assessment and prevention of falls, and point to possible shared neural substrate of cognitive and motor function.
cognition; falls; aging
Identifying quantitative gait markers of preclinical dementia may lead to new insights into early disease stages, improve diagnostic assessments and identify new preventive strategies.
To examine the relationship of quantitative gait parameters to decline in specific cognitive domains as well as the risk of developing dementia in older adults.
We conducted a prospective cohort study nested within a community based ageing study. Of the 427 subjects aged 70 years and older with quantitative gait assessments, 399 were dementia‐free at baseline.
Over 5 years of follow‐up (median 2 years), 33 subjects developed dementia. Factor analysis was used to reduce eight baseline quantitative gait parameters to three independent factors representing pace, rhythm and variability. In linear models, a 1 point increase on the rhythm factor was associated with further memory decline (by 107%), whereas the pace factor was associated with decline on executive function measured by the digit symbol substitution (by 29%) and letter fluency (by 92%) tests. In Cox models adjusted for age, sex and education, a 1 point increase on baseline rhythm (hazard ratio (HR) 1.48; 95% CI 1.03 to 2.14) and variability factor scores (HR 1.37; 95% CI 1.05 to 1.78) was associated with increased risk of dementia. The pace factor predicted the risk of developing vascular dementia (HR 1.60; 95% CI 1.06 to 2.41).
Our findings indicate that quantitative gait measures predict future risk of cognitive decline and dementia in initially non‐demented older adults.
Increased inflammatory activity and gait speed decline are common with aging, but the association between the two is not well established. The objective of this study was to determine the influence of inflammatory markers, interleukin-6 (IL-6), and tumor necrosis factor alpha, on gait speed performance and decline in older adults.
We conducted cross-sectional and longitudinal analyses of 333 adults aged 70 and older (61% women) with gait and biomarker assessments identified from participants in the Einstein Aging Study, a community-based aging study. Gait velocity measured at baseline and annual follow-up visits (median follow-up 2.3 years) was the main outcome.
At baseline, higher interleukin-6 levels were associated with slower gait velocity (estimate −4.90 cm/s, p = .008). Adjusted for age, gender, education, and medical illnesses, a one-unit increase in baseline log IL-6 levels was associated with a 0.98 cm/s faster gait speed decline per year (p = .002). The results remained significant after adjustments for additional potential confounders such as physical activity levels, body mass index, and medications. Participants in the highest IL-6 quartile had a 1.75 cm/s/year faster decline in gait velocity compared with those in the lowest quartile (p = .002). Tumor necrosis factor alpha was not associated with gait velocity at cross-section or with gait speed decline.
IL-6 levels are associated with gait performance in community residing seniors and predicts risk of gait speed decline in aging.
Mobility; Gait; Inflammation—Interleukin-6
The aim of this study was to assess the role of depression as a predictor of new onset of chronic migraine (CM) among persons with episodic migraine (EM). The American Migraine Prevalence and Prevention (AMPP) study followed 24,000 persons with severe headache identified in 2004. Using random-effects logistic regression, we modeled the probability that persons with EM in 2005 or 2006 would develop CM in the subsequent year. Depression was assessed in two ways, using a validated questionnaire (PHQ-9 score ≥15) and based on self-reported medical diagnosis. Analyses were adjusted for multiple covariates including sociodemographics, body mass index, headache pain intensity, headache frequency, migraine symptom severity, cutaneous allodynia, acute medication overuse, anti-depressant use and anxiety. Of 6,657 participants with EM in 2005, 160 (2.4 %) developed CM in 2006. Of 6,852 participants with EM in 2006, 144 (2.2 %) developed CM in 2007. In fully adjusted models, PHQ-9 defined depression was a significant predictor of CM onset [odds ratio (OR) = 1.65, 95 % CI 1.12–2.45]. There was a depression-dose effect; relative to participants with no depression or mild depression, those with moderate (OR = 1.77, 95 % CI 1.25–2.52), moderately severe (OR = 2.35, 95 % CI 1.53–3.62), and severe depression (OR = 2.53, 95 % CI 1.52–4.21) were at increased risk for the onset of CM. Among persons with EM, depression was associated with an increased risk of CM after adjusting for sociodemographic variables and headache characteristics. Depression preceded the onset of CM and risk increased with depression severity suggesting a potentially causal role though reverse causality cannot be excluded.
Electronic supplementary material
The online version of this article (doi:10.1007/s10194-012-0479-9) contains supplementary material, which is available to authorized users.
Depression; Chronic migraine; Epidemiology; Transformation; Migraine; Risk factors
To determine the prevalence of chronic pain in the elderly and its relationship with obesity, associated co-morbidities and risk factors.
A representative community sample of 840 elderly subjects age 70 or older.
We examined the prevalence of chronic pain and its relationship with obesity (categories defined by body mass index), other medical risk factors and psychiatric comorbidities. Chronic pain was defined by pain of at least moderate severity (≥ 4 on a 10-point scale) some, most or all of the time for the past three months.
The sample was mostly female (62.8%) and the average age was 80 years (range 70–101 years). The prevalence of chronic pain was 52% (39.7% in men; 58.9% in women). Those with chronic pain were more likely to report a diagnosis of depression (OR 2.5, 95%CI=1.40–4.55) and anxiety (OR 2.3, 95%CI=1.22–4.64). Compared to individuals with normal weight (BMI 18.5–24.9), obese subjects (BMI 30–34.9) were twice as likely (OR 2.1, 95%CI=1.33–3.28) while severely obese subjects (BMI ≥ 35) were more than four times as likely (OR 4.5, 95%CI=1.85–12.63) to have chronic pain. Obese subjects were significantly more likely to have chronic pain in the head, neck/shoulder, back, legs/feet, and abdomen/pelvis than non-obese subjects. In multivariate models, obesity (OR 2.0, 95%CI=1.27–3.26) and severe obesity (OR 4.1, 95%CI=1.57–10.82) were associated with chronic pain after adjusting for age, sex, diabetes, hypertension, depression, anxiety and education.
Chronic pain is common in this elderly population, affects women more than men and is highly associated with obesity.
Chronic Pain; Obesity; Elderly
This study examined the relationship between endogenous hormones and cognitive function in nondemented, ethnically-diverse community-dwelling older men enrolled in the Einstein Aging Study (EAS). All eligible participants (185 men, mean age=81 years) received neuropsychological assessment (Free and Cued Selective Reminding Test (FCSRT), Logical Memory (LM), Trail Making Test B (TMTB), Block Design (BD)) and provided blood samples for hormonal assays (total estradiol, total testosterone, calculated free testosterone index). Linear regression analysis adjusted for age, education, body mass index, and cardiovascular comorbidities indicated that men with high levels of total estradiol demonstrated better FCSRT verbal memory performance (β=0.17, p<0.02) compared to men with lower levels of total estradiol. The results remained unchanged when the model was further adjusted for ethnicity. We did not detect an association between testosterone and cognitive performance. These findings indicate that high levels of total estradiol in older men are associated with better performance on a cue-based, controlled learning test of verbal memory that is a sensitive predictor of dementia.
Hormones; Cognition; Memory; Men; Older Adults; Aging; Testosterone; Estradiol
Intravenous metoclopramide is effective as primary therapy for acute migraine but the optimal dose of this medication is not yet known.
This was a randomized, double-blind, dose finding study conducted on patients who presented to our emergency department (ED) meeting International Classification of Headache Disorders criteria for migraine without aura. We randomized patients to 10mg, 20mg, or 40mg of intravenous metoclopramide. We co-administered diphenhydramine to all patients to prevent extra-pyramidal side effects. The primary outcome was improvement in pain on an 11 point Numerical Rating Scale (NRS) at one hour. Secondary outcomes included sustained pain freedom at 48 hours and adverse effects.
In this study, 356 patients were randomized. Baseline demographics and headache features were comparable among the groups. At one hour, those who received 10mg improved by a mean of 4.7 NRS points (95%CI: 4.2, 5.2); those who received 20mg improved by 4.9 (95%CI: 4.4, 5.4), and those who received 40mg improved by 5.3(95%CI: 4.8, 5.9). Rates of 48 hour sustained pain freedom in the 10, 20, and 40mg groups were: 16% (95%CI:10,24%), 20% (95%CI:14,28%), and 21% (95%CI:15,29%), respectively. The most commonly occurring adverse event was drowsiness, which impaired function in 17% (95%CI: 13,21%) of the overall study population. Akathisia developed in 33 patients. Both drowsiness and akathisia were evenly distributed across the 3 arms of the study. One month later, no patient had developed tardive dyskinesia.
20mg or 40mg of metoclopramide are no better for acute migraine than 10mg of metoclopramide.
A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.
Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress.
The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing.
Cohort studies; Cognitive ageing; Data harmonisation; Dementia; International consortium; Mild cognitive impairment
Chronic pain is more common in the elderly and impairs functioning and quality of life. Though obesity, defined by body mass index (BMI), has been associated with pain prevalence among older adults, the mechanism of this association remains unclear. We examined components of the metabolic syndrome, insulin resistance, a marker of inflammation, and the presence of painful comorbidities as possible mediators of this association. Participants were 407 individuals age • 70 in the Einstein Aging Study. Chronic pain and pain over the last 3 months were defined using the Total Pain Index (TPI). Insulin resistance was modeled as fasting insulin, HOMA and QUICKI. High sensitivity C-reactive protein was used as a marker of inflammation. Cross-sectional logistic regression models were constructed to assess the associations of these factors with prevalent pain, adjusted for other known pain correlates. Prevalence of chronic pain was 52%. Of the clinical components of metabolic syndrome, central obesity was significantly associated with pain (OR 2.03, 95% CI 1.36-3.01). After adjustment for insulin resistance, inflammation, and pain-related comorbidities, central obesity predicted higher TPI scores (OR 1.55, 95% CI 1.04-2.33) and nearly doubled the risk of chronic pain (OR 1.70, 95% CI 1.05-2.75). Central obesity is the metabolic syndrome component showing the strongest independent association with pain, and the relationship is not explained by markers of insulin resistance or inflammation, nor by the presence of osteoarthritis or neuropathy.
Mutations in the leucine-rich repeat kinase 2 gene (LRRK2, PARK8) are the most commonly identified monogenic etiology of Parkinson disease (PD). Over-represented in the Ashkenazi Jewish (AJ) population, these mutations are transmitted in an autosomal dominant manner with age-dependent reduced penetrance. The natural history and penetrance of these mutations in the elderly is controversial and inadequately studied. We conducted a nested cohort study in a community-based aging study (the Einstein Aging Study, EAS). Six elderly, initially non-manifesting carriers (NMC) of the LRKK2 G2019S mutation were identified (average age 82.1±7.0, range 72.7-90.8), and five had available longitudinal data. We matched 5 non-carrier controls to each NMC and followed them for an average of 4.7 years with annual cognitive and motor examinations. PD was identified in one NMC at age 95 and in no control subjects. The remaining carriers did not differ from controls on motor scores at baseline or follow-up. The baseline Unified Parkinson's Disease Rating Scale motor subscore (UPDRS-III) in cases was 6.2±6.9 (range 1-19) and in controls was 4.5±6.6 (1-30), p=0.6; the mean difference in UPDRS-III slopes over time between cases and controls was 0.1±1.3 and was not statistically significant. Our data, while limited by a small sample size, show that in LRKK2 G2019S mutation carriers, phenoconversion to PD can occur late in life. However, most NMC have motor decline which indistinguishable from their age mates, suggesting that the larger subset of elderly non-manifesting carriers is not on the motor trajectory to disease.
LRRK2; Parkinson's disease; parkinsonism; non-manifesting carriers; penetrance; cognition; clinical
Chronic migraine (CM) and episodic migraine (EM) are part of the spectrum of migraine disorders, but they are distinct clinical entities. Population-based studies have shown that those with CM demonstrate higher individual and societal burden because they are significantly more disabled than those with EM and have greater impaired quality of life both inside and outside the home. Proper diagnosis of both conditions requires clearly defined clinical criteria. Diagnosis enables the initiation of appropriate treatments and risk-factor modification, which ultimately improve functional status and quality of life for persons with migraine. Recognizing that both disorders are on the spectrum of migraine, this review serves as a guide to define the disease state of CM as distinct from EM in terms of clinical, epidemiological, sociodemographic, and comorbidity profiles.
Chronic migraine; Episodic migraine; Epidemiological profiles; Sociodemographics; Risk factors; Treatment; Chronic daily headache; Chronification; Diagnosis
The natural history of lifespan cognitive performance and its late-life determinants have been studied from an array of perspectives. Significant insights come from psychological disciplines including cognitive, developmental, and neuropsychology, as well as from medical specialties such as geriatrics, neurology, psychiatry, neuroradiology and neuropathology which contribute to the growing interdisciplinary scientific field, cognitive neuroscience of aging. Our survey of longitudinal studies of aging suggests that disease-oriented investigations commonly do not adequately consider normative cognitive changes, while developmental studies do not sufficiently measure and model non-normative cognitive aging. We argue for an integrative perspective that considers both of these influences on cognitive trajectories, and present a series of methodological issues that have not been addressed comprehensively. We conclude that interdisciplinary methods from longitudinal observational studies should be leveraged to enable translational interventions to promote brain longevity.
cognitive aging; change point; robust norms; measurement burst
Multiple parenteral medications are used to treat migraine and other acute primary headaches in the emergency department (ED). Regardless of specific headache diagnosis, no medication eliminates the frequent recurrence of primary headache after ED discharge. It is uncertain which medication primary headache patients should be given upon discharge from an ED. The aim of this study was to compare the efficacy of oral sumatriptan to naproxen for treatment of post-ED recurrent primary headache.
This was a randomized, double-blind efficacy trial. We randomized patients to either naproxen 500mg or sumatriptan 100mg for headache recurrence following ED discharge. Patients were eligible if they received parenteral therapy for an acute exacerbation of a primary headache in the ED. Patients who met established criteria for migraine without aura were designated a priori as a homogenous subgroup of interest. We followed all patients by telephone 48 hours after ED discharge. The primary endpoint was the between-group difference in change in pain intensity over the 2-hour period following ingestion of either 500 mg naproxen or 100 mg sumatriptan. This difference was measured on a validated 11-point (0–10) verbal Numerical Rating Scale (NRS). Satisfaction with the medication and side effects were also assessed. Patients who met criteria for migraine without aura were analyzed twice according to a priori design: once as a homogenous subgroup and then again combined with all other primary headaches.
Of 410 patients randomized, 383 (93%) had outcome data available for analysis. 280 (73%, 95%CI: 68, 77% ) reported headache post-ED discharge and 196 (51%, 95%CI: 44, 58%), including 88 with migraine, took the investigational medication provided to them. The naproxen group improved by a mean of 4.3 NRS points, while the sumatriptan group improved by 4.1 (95%CI for difference of 0.2: −0.7, 1.1). Findings were virtually identical among the migraine subset (4.3 vs. 4.2 NRS points, 95%CI for difference of 0.1: −1.3, 1.5). 71% (95%CI: 62, 80%) of naproxen patients and 75% (95%CI: 66, 84%) of sumatriptan patients would want to take the same medication the next time. Side effect profiles were also comparable.
In this trial, nearly ¾ of patients reported headache recurrence within 48 hours of ED discharge. Naproxen 500 mg and sumatriptan 100 mg taken orally relieve post-ED recurrent primary headache and migraine comparably. Clinicians should be guided by medication costs, contraindications, and a patient’s previous experience with the medication.