Quantifying the extent of cognitive dysfunction in patients with intracranial tumors is important to monitor treatment effects and assess patients' needs. Inspection time, a measure of the efficiency of visual information processing, was evaluated, and its usefulness in patients with intracranial tumors was compared with that of other widely used cognitive tests. Newly presenting inpatients with supratentorial intracranial tumors (n = 118) underwent preoperative assessment using inspection time and a number of other measures of cognitive function, mood, and functional status. The brain tumor cohort was compared with patients admitted for elective spinal surgery (n = 85) and a healthy control group (n = 80). Analysis of covariance was used to compare the performance of the 3 groups. The brain tumor cohort had significantly lower inspection time scores than the spinal surgery group (P = .005) and the healthy volunteer control group (P < .001). The effect size was moderate. There was a large effect size of participant group for the Rey Auditory Verbal Learning Test, Digit Symbol-Coding, and Verbal Fluency (P = .002). The performance of patients with brain tumors was significantly worse than that of both of the control groups. Inspection time was well-tolerated by patients with intracranial tumors. However, inspection time is neither as easy to perform nor as sensitive as some other measures of cognitive function. Although its lack of any motor speed or coordination requirements, conceptual simplicity, repeatability, and relative lack of learning effect make inspection time a potentially useful tool in clinical neuro-oncology, practical considerations will limit its use.
brain tumor; cognitive assessment; inspection time; neuro-oncology
Two important consequences of the normal ageing process are sarcopenia (the age-related loss of muscle mass and function) and age-related cognitive decline. Existing data support positive relationships between muscle function, cognition and brain structure. However, studies investigating these relationships at older ages are lacking and rarely include a measure of muscle size. Here we test whether neck muscle size is positively associated with cognition and brain structure in older men.
We studied 51 healthy older men with mean age 73.8 (sd 1.5) years. Neck muscle cross-sectional area (CSA) was measured from T1-weighted MR-brain scans using a validated technique. We measured multiple cognitive domains including verbal and visuospatial memory, executive functioning and estimated prior cognitive ability. Whole brain, ventricular, hippocampal and cerebellar volumes were measured with MRI. General linear models (ANCOVA) were performed.
Larger neck muscle CSA was associated with less whole brain atrophy (t = 2.86, p = 0.01, partial eta squared 17%). Neck muscle CSA was not associated with other neuroimaging variables or current cognitive ability. Smaller neck muscle CSA was unexpectedly associated with higher prior cognition (t = −2.12, p < 0.05, partial eta squared 10%).
In healthy older men, preservation of whole brain volume (i.e. less atrophy) is associated with larger muscle size. Longitudinal ageing studies are now required to investigate these relationships further.
Sarcopenia; Cognition; Aging; Muscle cross-sectional area; Brain volume
Good bone and joint health is essential for the physical tasks of daily living and poorer indicators of physical capability in older adults have been associated with increased mortality rates. Genetic variants of indicators of bone and joint health may be associated with measures of physical capability.
As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women aged between 52 and 90 + years from six UK cohorts were genotyped for a polymorphism associated with serum calcium (rs1801725, CASR), two polymorphisms associated with bone mineral density (BMD) (rs2941740, ESR1 and rs9594759, RANKL) and one associated with osteoarthritis risk rs3815148 (COG5). Meta-analysis was used to pool within-study effects of the associations between each of the polymorphisms and measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.
Few important associations were observed among the several tests. We found that carriers of the serum calcium-raising allele had poorer grip strength compared with non-carriers (pooled p = 0.05, n = 11,239) after adjusting for age and sex. Inconsistent results were observed for the two variants associated with BMD and we found no evidence for an association between rs3815148 (COG5) and any of the physical capability measures.
Our findings suggest elevated serum calcium levels may lead to lower grip strength, though this requires further replication. Our results do not provide evidence for a substantial influence of these variants in ESR1, RANKL and COG5 on physical capability in older adults.
► We examined associations between bone-related genotypes and physical capability. ► We conducted a meta-analysis on 12,836 middle-age adults. ► We found CASR may be associated with grip strength. ► No substantial support for specific bone mineral density variants and physical capability.
BMD, bone mineral density; OA, osteoarthritis; BMI, body mass index; SNP, single nucleotide polymorphism; CaPS, Caerphilly Prospective Study; ELSA, English Longitudinal Study of Ageing; HAS, Hertfordshire Ageing Study; HCS, Hertfordshire Cohort Study; LBC1921, The Lothian Birth Cohort 1921; NSHD, National Survey of Health and Development; HWE, Hardy–Weinberg equilibrium; WHR, waist–hip ratio; GWAS, genome-wide association studies; Aging; Grip strength; Calcium; Bone mineral density; Osteoarthritis
The adverse effects of advancing maternal age on offspring's health and development are well understood. Much less is known about the impact of paternal age.
We explored paternal age-offspring cognition associations in 772 participants from the West of Scotland Twenty-07 study. Offspring cognitive ability was assessed using Part 1 of the Alice Heim 4 (AH4) test of General Intelligence and by reaction time (RT).
There was no evidence of a parental age association with offspring RT. However, we observed an inverse U-shaped association between paternal age and offspring AH4 score with the lowest scores observed for the youngest and oldest fathers. Adjustment for parental education and socioeconomic status somewhat attenuated this association. Adjustment for number of, particularly older, siblings further reduced the scores of children of younger fathers and appeared to account for the lower offspring scores in the oldest paternal age group.
We observed a paternal age association with AH4 but not RT, a measure of cognition largely independent of social and educational experiences. Factors such as parental education, socioeconomic status and number of, particularly older, siblings may play an important role in accounting for paternal age-AH4 associations. Future studies should include parental intelligence.
The ACTN3 R577X (rs1815739) genotype has been associated with athletic status and muscle phenotypes, though not consistently. Our objective was to conduct a meta-analysis of the published literature on athletic status and investigate its associations with physical capability in several new population-based studies. Relevant data were extracted from studies in the literature, comparing genotype frequencies between controls and sprint/power and endurance athletes. For lifecourse physical capability, data were used from two studies of adolescents and seven studies in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, involving individuals aged between 53 and 90+ years. We found evidence from the published literature to support the hypothesis that in Europeans the RR genotype is more common among sprint/power athletes compared with their controls. There is currently no evidence that the X allele is advantageous to endurance athleticism. We found no association between R577X and grip strength (p-value=0.09, n=7672 in males; p-value=0.90, n=7839 in females), standing balance, timed get up and go or chair rises in our studies of physical capability. The ACTN3 R577X genotype is associated with sprint/power athletic status in Europeans, but does not appear to be associated with objective measures of physical capability in the general population.
ACTN3; Actinin-3; athlete; aging; SNP; grip strength
Physical, emotional, and psychosocial wellbeing are important domains of function. The aims of this study were to explore the existence of separable groups among 70-year olds with scores representing physical function, perceived quality of life, and emotional wellbeing, and to characterise any resulting groups using demographic, personality, cognition, health and lifestyle variables.
We used latent class analysis (LCA) to identify possible groups.
Results suggested there were 5 groups. These included High (n = 515, 47.2% of the sample), Average (n = 417, 38.3%), and Poor Wellbeing (n = 37, 3.4%) groups. The two other groups had contrasting patterns of wellbeing: one group scored relatively well on physical function, but low on emotional wellbeing (Good Fitness/ Low Spirits,n = 60, 5.5%), whereas the other group showed low physical function but relatively well emotional wellbeing (Low Fitness/Good Spirits, n = 62, 5.7%). Salient characteristics that distinguished all the groups included smoking and drinking behaviours, personality, and illness.
Despite there being some evidence of these groups, the results also support a largely one-dimensional construct of wellbeing in old age—for the domains assessed here—though with some evidence that some individuals have uneven profiles.
Physical wellbeing; Psychosocial wellbeing; Profiles; Latent class analysis
The ACTN3 R577X (rs1815739) genotype has been associated with
athletic status and muscle phenotypes, although not consistently. Our objective
was to conduct a meta-analysis of the published literature on athletic status
and investigate its associations with physical capability in several new
population-based studies. Relevant data were extracted from studies in the
literature, comparing genotype frequencies between controls and sprint/power and
endurance athletes. For life course physical capability, data were used from two
studies of adolescents and seven studies in the Healthy Ageing across the Life
Course (HALCyon) collaborative research program, involving individuals aged
between 53 and 90+ years. We found evidence from the published literature
to support the hypothesis that in Europeans the RR genotype is more common among
sprint/power athletes compared with their controls. There is currently no
evidence that the X allele is advantageous to endurance athleticism. We found no
association between R577X and grip strength (P = 0.09,
n = 7,672 in males; P =
0.90, n = 7,839 in females), standing balance, timed get
up and go, or chair rises in our studies of physical capability. The
ACTN3 R577X genotype is associated with sprint/power
athletic status in Europeans, but does not appear to be associated with
objective measures of physical capability in the general population. Hum Mutat
32:1–11, 2011. © 2011 Wiley-Liss, Inc.
ACTN3; Actinin-3; athlete; aging; SNP; grip strength
The search for biomarkers of aging (BoAs) has been largely unsuccessful to-date and there is widespread skepticism about the prospects of finding any that satisfy the criteria developed by the American Federation of Aging Research. This may be because the criteria are too strict or because a composite measure might be more appropriate. Telomere length has attracted a great deal of attention as a candidate BoA. We investigate whether it meets the criteria to be considered as a single biomarker of aging, and whether it makes a useful contribution to a composite measure.
Using data from a large population based study, we show that telomere length is associated with age, with several measures of physical and cognitive functioning that are related to normal aging, and with three measures of overall health. In the majority of cases, telomere length adds predictive power to that of age, although it was not nearly as good a predictor overall. We used principal components analysis to form two composites from the measures of functioning, one including telomere length and the other not including it. These composite BoAs were better predictors of the health outcomes than chronological age. There was little difference between the two composites.
Telomere length does not satisfy the strict criteria for a BoA, but does add predictive power to that of chronological age. Equivocal results from previous studies might be due to lack of power or the choice of measures examined together with a focus on single biomarkers. Composite biomarkers of aging have the potential to outperform age and should be considered for future research in this area.
Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).
Methodology and Principal Findings
Cross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p>0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p>0.05 for depression scores).
Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.
To examine the relation of scores on tests of mental ability across childhood with established risk factors for premature mortality at the age of 30 years.
A prospective cohort study based on members of the British Cohort Study born in Great Britain in 1970 who had complete data on IQ scores at five (N = 8203) or 10 (N = 8171) years of age and risk factors at age 30 years.
In sex‐adjusted analyses, higher IQ score at age 10 years was associated with a reduced prevalence of current smoking (ORper 1 SD advantage in IQ 0.84; 95% CI 0.80, 0.88), overweight (0.88; 0.84, 0.92), obesity (0.84; 0.79, 0.92), and hypertension (0.90; 0.83, 0.98), and an increased likelihood of having given up smoking by the age of 30 years (1.25; 1.18, 1.24). These gradients were attenuated after adjustment for markers of socioeconomic circumstances across the life course, particularly education. There was no apparent relationship between IQ and diabetes. Essentially the same pattern of association was evident when the predictive value of IQ scores at five years of age was examined.
The mental ability–risk factor gradients reported in the present study may offer some insights into the apparent link between low pre‐adult mental ability and premature mortality.
mental ability; risk factors; mortality
To examine the effects of acute insulin-induced hypoglycemia on spatial cognitive abilities in adult humans with type 1 diabetes.
RESEARCH DESIGN AND METHODS
Sixteen adults with type 1 diabetes underwent two counterbalanced experimental sessions: euglycemia (blood glucose 4.5 mmol/l [81 mg/dl]) and hypoglycemia (2.5 mmol/l [45 mg/dl]). Arterialized blood glucose levels were maintained using a hyperinsulinemic glucose clamp technique. During each session, subjects underwent detailed assessment of spatial abilities from the Kit of Factor-Referenced Cognitive Tests and two tests of general cognitive function.
Spatial ability performance deteriorated significantly during hypoglycemia. Results for the Hidden Patterns, Card Rotations, Paper Folding, and Maze Tracing tests were all impaired significantly (P ≤ 0.001) during hypoglycemia, as were results for the Cube Comparisons Test (P = 0.03). The Map Memory Test was not significantly affected by hypoglycemia.
Hypoglycemia is a common side effect of insulin therapy in individuals with type 1 diabetes, and spatial abilities are of critical importance in day-to-day functioning. The deterioration in spatial abilities observed during modest experimental hypoglycemia provides novel information on the cerebral hazards of hypoglycemia that has potential relevance to everyday activities.
Several age-related traits are associated with shorter telomeres, the structures that cap the end of linear chromosomes. A common polymorphism near the telomere maintenance gene TERT has been associated with several cancers, but relationships with other ageing traits such as physical capability have not been reported.
As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women aged between 44 and 90 years from 9 UK cohorts were genotyped for the single nucleotide polymorphism (SNP) rs401681. We then investigated relationships between the SNP and 30 age-related phenotypes, including cognitive and physical capability, blood lipid levels and lung function, pooling within-study genotypic effects in meta-analyses.
No significant associations were found between the SNP and any of the cognitive performance tests (e.g. pooled beta per T allele for word recall z-score=0.02, 95% CI: -0.01- 0.04, p-value=0.12, n=18,737), physical performance tests (e.g. pooled beta for grip strength=-0.02, 95% CI:-0.045- 0.006, p-value=0.14, n=11,711), blood pressure, lung function or blood test measures. Similarly, no differences in observations were found when considering follow-up measures of cognitive or physical performance after adjusting for its measure at an earlier assessment.
The lack of associations between SNP rs401681 and a wide range of age-related phenotypes investigated in this large multi-cohort study suggests that whilst this SNP may be associated with cancer, it is not an important contributor to other markers of ageing.
Aging; ageing; middle-aged; telomere; cognition; physical
Background A number of prospective cohort studies have examined the association between intelligence in childhood or youth and life expectancy in adulthood; however, the effect size of this association is yet to be quantified and previous reviews require updating.
Methods The systematic review included an electronic search of EMBASE, MEDLINE and PSYCHINFO databases. This yielded 16 unrelated studies that met inclusion criteria, comprising 22 453 deaths among 1 107 022 participants. Heterogeneity was assessed, and fixed effects models were applied to the aggregate data. Publication bias was evaluated, and sensitivity analyses were conducted.
Results A 1-standard deviation (SD) advantage in cognitive test scores was associated with a 24% (95% confidence interval 23–25) lower risk of death, during a 17- to 69-year follow-up. There was little evidence of publication bias (Egger’s intercept = 0.10, P = 0.81), and the intelligence–mortality association was similar for men and women. Adjustment for childhood socio-economic status (SES) in the nine studies containing these data had almost no impact on this relationship, suggesting that this is not a confounder of the intelligence–mortality association. Controlling for adult SES in five studies and for education in six studies attenuated the intelligence–mortality hazard ratios by 34 and 54%, respectively.
Conclusions Future investigations should address the extent to which attenuation of the intelligence–mortality link by adult SES indicators is due to mediation, over-adjustment and/or confounding. The explanation(s) for association between higher early-life intelligence and lower risk of adult mortality require further elucidation.
Intelligence; mortality; meta-analysis; socio-economic factors; systematic review
This glossary provides a guide to some concepts, findings and issues of discussion in the new field of research in which intelligence test scores are associated with mortality and morbidity. Intelligence tests are devised and studied by differential psychologists. Some of the major concepts in differential psychology are explained, especially those regarding cognitive ability testing. Some aspects of IQ (intelligence) tests are described and some of the major tests are outlined. A short guide is given to the main statistical techniques used by differential psychologists in the study of human mental abilities. There is a discussion of common epidemiological concepts in the context of cognitive epidemiology.
A series of studies have shown an association between high childhood IQ scores and reduced rates of total mortality in adulthood. Several mechanisms have been advanced to explain these relationships, including mediation via established risk factors. This study examines the association between childhood IQ and a range of established physiological and behavioural risk factors for premature mortality in adulthood.
Design, setting and participants
In 1962, 12 150 children took part in a school‐based survey when their IQ scores were extracted from educational records. When re‐surveyed forty years later (n = 7183; 63.7% response), they self‐reported information on risk factors for premature mortality (smoking, heavy alcohol consumption, obesity, height, hypertension and diabetes).
In sex‐adjusted analyses based on an analytical sample of 5340 (2687 women), higher childhood IQ scores were associated with a decreased prevalence of ever having smoked regularly in adulthood (ORper SD increase in IQ (95% CI): 0.77 (0.73 to 0.81)), heavy alcohol consumption (0.89 (0.84 to 0.94)), obesity (0.78 (0.72 to 0.83)) and overweight (0.86 (0.81 to 0.91)). Higher IQ scores were similarly related to a reduced prevalence of short stature and higher rates of smoking cessation in smokers; effects that were stronger in women (p value for interaction: ⩽0.04). Adjusting for indicators of early and, particularly, later‐life socioeconomic circumstances led to heavy attenuation of these gradients with statistical significance at conventional levels lost in most analyses.
The IQ–risk factor gradients reported may offer some insights into the apparent link between high pre‐adult IQ and reduced mortality rates.
Both type 2 diabetes and glucocorticoid therapy are highly prevalent. Although people with type 2 diabetes may be more susceptible to adverse effects of glucocorticoids, and it is recommended that glucocorticoid therapy is avoided for fear of worsening glycaemic control, the extent to which this advice is followed and the consequences when glucocorticoids are prescribed are poorly documented. The aim was to assess the characteristics of people with type 2 diabetes prescribed glucocorticoids in a real-world setting and to quantify resulting adverse effects.
Cross-sectional cohort study.
Cardiometabolic variables, body fat distribution, cognitive function and mood were studied in the 1066 participants of the Edinburgh Type 2 Diabetes Study, of whom 162 (15%) were taking systemic, topical or inhaled glucocorticoids.
Glucocorticoid therapy was more common in women and in smokers but was not avoided in patients with diabetic complications or cardiovascular risk factors. People taking glucocorticoids were more centrally obese with slightly higher HbA1c and total serum cholesterol but were no more likely to have hepatic steatosis or hypertension. Glucocorticoid treatment was associated with substantially lower mood and greater anxiety. Women taking glucocorticoid therapy were twice as likely to report depressive symptoms compared with those not taking treatment. Glucocorticoid therapy was also associated with poorer cognitive function among those with subclinical atherosclerosis, as indicated by low ankle–brachial pressure index.
Glucocorticoids are prescribed commonly for people with type 2 diabetes despite being associated with adverse indices of glycaemic control, cardiovascular risk factors, mood and cognitive function.
Prevailing psychometric theories of intelligence posit that individual differences in cognitive performance are attributable to three main sources of variance: the general factor of intelligence (g), cognitive ability domains, and specific test requirements and idiosyncrasies. Cortical thickness has been previously associated with g. In the present study, we systematically analyzed associations between cortical thickness and cognitive performance with and without adjusting for the effects of g in a representative sample of children and adolescents (N = 207, Mean age = 11.8; SD = 3.5; Range = 6 to 18.3 years). Seven cognitive tests were included in a measurement model that identified three first-order factors (representing cognitive ability domains) and one second-order factor representing g. Residuals of the cognitive ability domain scores were computed to represent g-independent variance for the three domains and seven tests. Cognitive domain and individual test scores as well as residualized scores were regressed against cortical thickness, adjusting for age, gender and a proxy measure of brain volume. g and cognitive domain scores were positively correlated with cortical thickness in very similar areas across the brain. Adjusting for the effects of g eliminated associations of domain and test scores with cortical thickness. Within a psychometric framework, cortical thickness correlates of cognitive performance on complex tasks are well captured by g in this demographically representative sample.
General intelligence; cognitive abilities; cognitive performance; cognitive domains; factor analysis; cortical thickness
Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.
As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.
Few important associations were observed among the several tests. We found evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82–0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits.
Our findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.
Cerebral microvascular disease associated with type 2 diabetes may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral microcirculations; a hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with type 2 diabetes.
RESEARCH DESIGN AND METHODS
In the population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60–75 years with type 2 diabetes underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using a modification of the Early Treatment of Diabetic Retinopathy Scale.
After age and sex adjustment, a significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency, mental flexibility, and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, sociodemographic characteristics, cardiovascular risk factors, and macrovascular disease.
DR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation.
Interest in measuring functional status among nondisabled older adults has increased in recent years. This is, in part, due to the notion that adults identified as 'high risk' for functional decline portray a state that is potentially easier to reverse than overt disability. Assessing relatively healthy older adults with traditional self-report measures (activities of daily living) has proven difficult because these instruments were initially developed for institutionalised older adults. Perhaps less evident, are problems associated with change scores and the potential for 'construct under-representation', which reflects the exclusion of important features of the construct (e.g., disability). Furthermore, establishing a formal hierarchy of functional status tells more than the typical simple summation of functional loss, and may have predictive value to the clinician monitoring older adults: if the sequence task difficulty is accelerated or out of order it may indicate the need for interventions.
This review identified studies that employed item response theory (IRT) to examine or revise functional status scales. IRT can be used to transform the ordinal nature of functional status scales to interval level data, which serves to increase diagnostic precision and sensitivity to clinical change. Furthermore, IRT can be used to rank items unequivocally along a hierarchy based on difficulty. It should be noted that this review is not concerned with contrasting IRT with more traditional classical test theory methodology.
A systematic search of four databases (PubMed, Embase, CINAHL, and PsychInfo) resulted in the review of 2,192 manuscripts. Of these manuscripts, twelve met our inclusion/exclusion requirements and thus were targeted for further inspection.
Manuscripts presented in this review appear to summarise gerontology's best efforts to improve construct validity and content validity (i.e., ceiling effects) for scales measuring the early stages of activity restriction in community-dwelling older adults. Several scales in this review were exceptional at reducing ceiling effects, reducing gaps in coverage along the construct, as well as establishing a formal hierarchy of functional decline. These instrument modifications make it plausible to detect minor changes in difficulty for IADL items positioned at the edge of the disability continuum, which can be used to signal the onset of progressive type disability in older adults.
Alzheimer's disease patients have deficits in specific cognitive domains, and susceptibility genes for this disease may influence human cognition in nondemented individuals. To evaluate the role of Alzheimer's disease-linked genetic variation on cognition and normal cognitive ageing, we investigated two Scottish cohorts for which assessments in major cognitive domains are available: the Lothian Birth Cohort of 1921 and the Lothian Birth Cohort of 1936, consisting of 505 and 998 individuals, respectively. 158 SNPs from eleven genes were evaluated. Single SNP analyses did not reveal any statistical association after correction for multiple testing. One haplotype from TRAPPC6A was associated with nonverbal reasoning in both cohorts and combined data sets. This haplotype explains a small proportion of the phenotypic variability (1.8%). These findings warrant further investigation as biological modifiers of cognitive ageing.
People with type 2 diabetes are at increased risk of cognitive impairment but the mechanism is uncertain. Elevated glucocorticoid levels in rodents and humans are associated with cognitive impairment. We aimed to determine whether fasting cortisol levels are associated with cognitive ability and estimated lifetime cognitive change in an elderly population with type 2 diabetes.
RESEARCH DESIGN AND METHODS
This was a cross-sectional study of 1,066 men and women aged 60–75 years with type 2 diabetes, living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study). Cognitive abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility were tested, and a general cognitive ability factor, g, was derived. Prior intelligence was estimated from vocabulary testing, and adjustment for scores on this test was used to estimate lifetime cognitive change. Relationships between fasting morning plasma cortisol levels and cognitive ability and estimated cognitive change were tested. Models were adjusted for potential confounding and/or mediating variables including metabolic and cardiovascular variables.
In age-adjusted analyses, higher fasting cortisol levels were not associated with current g or with performance in individual cognitive domains. However, higher fasting cortisol levels were associated with greater estimated cognitive decline in g and in tests of working memory and processing speed, independent of mood, education, metabolic variables, and cardiovascular disease (P < 0.05).
High morning cortisol levels in elderly people with type 2 diabetes are associated with estimated age-related cognitive change. Strategies targeted at lowering cortisol action may be useful in ameliorating cognitive decline in individuals with type 2 diabetes.
To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes.
RESEARCH DESIGN AND METHODS
A cross-sectional study of 1,066 men and women aged 60–75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary–based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing.
Higher IL-6 and TNF-α levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients −0.074 to −0.173 (P < 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, IL-6 remained associated with three of the cognitive tests and with g.
In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline.
Obesity is more common among the less educated, suggesting education-related environmental triggers. Such triggers may act differently dependent on genetic and environmental predisposition to obesity. In a Danish Twin Registry survey, 21,522 twins of same-sex pairs provided zygosity, height, weight, and education data. Body mass index (BMI = kg weight/ m height2) was used to measure degree of obesity. We used quantitative genetic modeling to examine how genetic and shared and nonshared environmental variance in BMI differed by level of education and to estimate how genetic and shared and nonshared environmental correlations between education and BMI differed by level of education, analyzing women and men separately. Correlations between education and BMI were −.13 in women, −.15 in men. High BMI's were less frequent among well-educated participants, generating less variance. In women, this was due to restriction of all forms of variance, overall by a factor of about 2. In men, genetic variance did not vary with education, but results for shared and nonshared environmental variance were similar to those for women. The contributions of the shared environment to the correlations between education and BMI were substantial among the well-educated, suggesting importance of familial environmental influences common to high education and lower BMI. Family influence was particularly important in linking high education and lower levels of obesity.
To evaluate two psychometric properties of SF-36, namely unidimensionality and reliability.
The data are from three cohorts in the HALCyon collaborative research programme into healthy ageing: Aberdeen Birth Cohort 1936 (n = 428), Hertfordshire Ageing Study (n = 358) and Hertfordshire Cohort Study (n = 3,216). The Mokken scaling model was applied to each sub-scale of SF-36 to evaluate unidimensionality as indicated by scalability. The lower bound for internal consistency reliability was determined by Cronbach’s alpha.
All six sub-scales of SF-36, with the exception of general health (GH) and mental health (MH), demonstrated strong scalability (0.5 ≤ H < 1). The results were consistent across all 3 cohorts. Both GH and MH showed medium scalability (0.4 ≤ H <0.55), although individual items ‘sick easier..’, ‘as healthy as..’ and ‘expect to get worse’ of the GH sub-scale and ‘nervous’, ‘happy’ in the MH sub-scale had low scalability (H < 0.4) in the oldest cohort (aged 73–83). Cronbach’s alphas for all sub-scales were between 0.70 and 0.92.
The unidimensionality and reliability of the sub-scales of SF-36 are sufficient to make this a useful measure of health-related quality of life in older people. Caution is needed when interpreting the results for GH and MH in the oldest cohort due to the poor unidimensionality.
SF-36; Psychometric properties; Unidimensionality; Reliability; Cronbach’s alpha; Mokken scaling