Nicolas Cherbuin

Body mass index in midlife and late‐life as a risk factor for dementia: a meta‐analysis of prospective studies

The relationship between body mass index (BMI) (in midlife and late‐life) and dementia was investigated in meta‐analyses of 16 articles reporting on 15 prospective studies. Follow‐ups ranged from 3.2 to 36.0 years. Meta‐analyses were conducted on samples including 25 624 participants evaluated for Alzheimers disease (AD), 15 435 participants evaluated for vascular dementia (VaD) and 30 470 followed for any type of dementia (Any Dementia). Low BMI in midlife was associated with 1.96 [95% confidence interval (CI): 1.32, 2.92] times the risk of developing AD. The pooled relative risks for AD, VaD and Any Dementia for overweight BMI in midlife compared with normal BMI were 1.35 (95% CI:1.19, 1.54), 1.33 (95% CI: 1.02, 1.75) and 1.26 (95% CI: 1.10, 1.44), respectively. The pooled relative risks of AD and Any Dementia for obese BMI in midlife compared to normal BMI were 2.04 (95% CI: 1.59, 2.62) and 1.64 (95% CI: 1.34, 2.00), respectively. Continuous BMI in late‐life was not associated with dementia. Small numbers of studies included in pooled analyses reduce generalizability of findings, and emphasize the need for publication of additional findings. We conclude that underweight, overweight and obesity in midlife increase dementia risk. Further research evaluating late‐life BMI and dementia is required.

Cohort Profile: The PATH through life project

Centre for Mental Health Research, Australian National University, Canberra, ACT, Australia, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia, Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Melbourne, Victoria, Australia and Australian Demographic and Social Research Institute, Australian National University, Canberra, ACT, Australia

A Population-Based Study of Attention Deficit/Hyperactivity Disorder Symptoms and Associated Impairment in Middle-Aged Adults

Attention deficit/hyperactivity disorder (ADHD) is the most prevalent childhood psychiatric condition. It frequently persists into adulthood and can have serious health and other adverse consequences. The majority of previous adult ADHD studies have focused on young adults so that relatively little is known about ADHD symptoms and their effects in mid and late life. In addition, effects of subclinical levels of attention deficit and hyperactivity have not been studied in detail. In this study we investigated ADHD symptoms and related impairment in a large population-based sample of middle-aged Australian adults (n = 2091; 47% male). Applying the WHO adult ADHD Self Report Screener (ASRS) we observed that 6.2% of participants had scores that were previously associated with ADHD diagnosis. No significant gender difference in the distribution of ASRS scores was observed. Multiple regression analyses indicated strong positive correlations between symptoms of ADHD and depression/anxiety and significant negative associations (p<0.01) with employment, financial stress, relationship quality, health and well-being measures in this age group. Importantly, associations were highly significant even when few ADHD symptoms were reported. Compared to the hyperactivity component, the inattention trait was particularly strongly associated and remained significant after controlling for depression/anxiety symptoms. Our study confirms previous findings and significantly adds to existing literature especially for an age-group that has not been well-studied. Our results suggest that ADHD symptoms continue to be associated with ill-health and functional impairment in mid-life and are, therefore, likely to be a major, previously unrecognized source of late-life morbidity with associated social and economic costs. Thus, there is a compelling need for better understanding and development of age-appropriate approaches to the diagnosis and treatment of ADHD in mid- to late-life.

When more is less: Associations between corpus callosum size and handedness lateralization

Although not consistently replicated, a substantial number of studies suggest that left-handers have larger callosal regions than right-handers. We challenge this notion and propose that callosal size is not linked to left-handedness or right-handedness per se but to the degree of handedness lateralization. To test this hypothesis, we investigated the thickness of the corpus callosum in a large data set (n=361). We analyzed the correlations between callosal thickness and the degree of handedness lateralization in 324 right-handers and 37 left-handers at 100 equidistant points across the corpus callosum. We revealed significant negative correlations within the anterior and posterior midbody suggesting that larger callosal dimensions in these regions are associated with a weaker handedness lateralization. Significant positive correlations were completely absent. In addition, we compared callosal thickness between moderately lateralized left-handers (n=37) and three equally sized groups (n=37) of right-handers (strongly, moderately, and weakly lateralized). The outcomes of these group analyses confirmed the negative association between callosal size and handedness lateralization, although callosal differences between right- and left-handers did not reach statistical significance. This suggests that callosal differences are rather small, if examined as a dichotomy between two handedness groups. Future studies will expand this line of research by increasing the number of left-handers to boost statistical power and by combining macro- and microstructural, as well as functional and behavioral measurements to identify the biological mechanisms linking callosal morphology and handedness lateralization.

The Mediterranean Diet is Not Related to Cognitive Change in a Large Prospective Investigation: The PATH Through Life Study

OBJECTIVE To determine whether the Mediterranean diet and other dietary variables are predictors of transition from healthy cognitive aging to mild cognitive impairment and cognitive decline. DESIGN Longitudinal. PARTICIPANTS We assessed 1528 individuals, aged 60-64 years, who were participating in a prospective epidemiological study of mental health and aging. We tested participants at two time points, 4 years apart, for mild cognitive impairment using either the International Consensus Criteria, impairment on the Clinical Dementia Rating scale (Clinical Dementia Rating: 0.5), or any of a suite of criteria sets (any mild cognitive disorder). We used logistic regression to assess the dietary predictors of conversion to clinical diagnoses and multiple regression to identify the predictors of cognitive decline (change in global cognition) in healthy participants. RESULTS Of the 1528 participants with no cognitive impairment in the first wave of assessment and complete data, 10 participants were diagnosed with mild cognitive impairment, 19 with Clinical Dementia Rating 0.5, and 37 participants presented with any mild cognitive disorder at follow-up. Adherence to Mediterranean diet was not found to be protective against cognitive decline but excessive caloric intake, and high intake of monounsaturated fats was predictive of mild cognitive impairment. CONCLUSIONS In this large longitudinal investigation of generally healthy individuals Mediterranean diet was not found to be protective of cognitive decline.

In Vivo Hippocampal Measurement and Memory: A Comparison of Manual Tracing and Automated Segmentation in a Large Community-Based Sample

While manual tracing is the method of choice in measuring hippocampal volume, its time intensive nature and proneness to human error make automated methods attractive, especially when applied to large samples. Few studies have systematically compared the performance of the two techniques. In this study, we measured hippocampal volumes in a large (N = 403) population-based sample of individuals aged 44–48 years using manual tracing by a trained researcher and automated procedure using Freesurfer (http://surfer.nmr.mgh.harvard.edu) imaging suite. Results showed that absolute hippocampal volumes assessed with these methods were significantly different, with automated measures using the Freesurfer software suite being significantly larger, by 23% for the left and 29% for the right hippocampus. The correlation between the two methods varied from 0.61 to 0.80, with lower correlations for hippocampi with visible abnormalities. Inspection of 2D and 3D models suggested that this difference was largely due to greater inclusion of boundary voxels by the automated method and variations in subiculum/entorhinal segmentation. The correlation between left and right hippocampal volumes was very similar by the two methods. The relationship of hippocampal volumes to selected sociodemographic and cognitive variables was not affected by the measurement method, with each measure showing an association with memory performance and suggesting that both were equally valid for this purpose. This study supports the use of automated measures, based on Freesurfer in this instance, as being sufficiently reliable and valid particularly in the context of larger sample sizes when the research question does not rely on ‘true’ hippocampal volumes.

Higher normal fasting plasma glucose is associated with hippocampal atrophy The PATH Study

Objectives: Substantial evidence showing an association between type 2 diabetes (T2D) and cerebral atrophy, cognitive impairment, and dementia is accumulating. However, relatively little is known about the subclinical effects of high plasma glucose levels within the normal range. The aim of this study was to investigate the association between plasma glucose levels and hippocampal and amygdalar atrophy in a sample of 266 cognitively healthy individuals free of T2D, aged 60–64 years, taking part in a longitudinal study of aging. Methods: Fasting plasma glucose was assessed at wave 1. Hippocampal and amygdalar volumes were manually traced on 1.5 T MRI scans collected at wave 1 and at wave 2 4 years later. General linear model analyses were used to assess the relationship between plasma glucose and incident medial temporal lobe atrophy after controlling for a range of sociodemographic and health variables. Results: Plasma glucose levels were found to be significantly associated with hippocampal and amygdalar atrophy and accounted for 6%–10% in volume change after controlling for age, sex, body mass index, hypertension, alcohol, and smoking. Conclusions: High plasma glucose levels within the normal range (<6.1 mmol/L) were associated with greater atrophy of structures relevant to aging and neurodegenerative processes, the hippocampus and amygdala. These findings suggest that even in the subclinical range and in the absence of diabetes, monitoring and management of plasma glucose levels could have an impact on cerebral health. If replicated, this finding may contribute to a reevaluation of the concept of normal blood glucose levels and the definition of diabetes.

Neuroimaging and APOE Genotype: A Systematic Qualitative Review

Apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer’s disease (AD) and has also been implicated in cardiovascular disease, cognitive decline and cognitive changes in healthy ageing. The aim of this paper is to systematically review and critically assess the association between the APOE genotype and structural/functional cerebral changes as evidenced by brain imaging studies. A second aim is to determine whether these observed associations between APOE and the brain reflect changes which are consistent with the progression of AD neurodegenerative changes described in Braak stages. A search of Pubmed, Psycinfo, and Web of Science databases identified 64 articles available for qualitative review. The review found that presence of the APOE Ε4 allele is associated with (1) hippocampal, amygdalar and entorhinal cortex atrophy, (2) increased brain atrophy, (3) increased white matter hyperintensity volumes and (4) altered cerebral blood flow and glucose metabolism patterns. It is possible that there are critical age ranges when these effects are evident and that the APOE Ε2 genotype might present a risk. We conclude that structural brain change is associated with the APOE genotype and that it is more salient in younger ageing individuals.

Dietary patterns and depressive symptoms over time: examining the relationships with socioeconomic position, health behaviours and cardiovascular risk.

Introduction Recent research suggests that diet quality influences depression risk; however, a lack of experimental evidence leaves open the possibility that residual confounding explains the observed relationships. The aim of this study was to document the cross-sectional and longitudinal associations between dietary patterns and symptoms of depression and to undertake a detailed examination of potential explanatory factors, particularly socioeconomic circumstances, in the diet-depression relationship. Methods Data were drawn from the Personality and Total Health (PATH) Through Life Study, a longitudinal community study following three age cohorts (20+; 40+; 60+yrs) from south-eastern Australia over three assessment periods (n = 3663). Regression analyses evaluated the cross-sectional and longitudinal relationships between dietary patterns, depressive symptoms, age, detailed measures of socioeconomic circumstances, other health behaviours, and cardiovascular risk factors. Results The lowest tertile of prudent (healthy) dietary pattern and the highest tertile of western (unhealthy) dietary pattern were associated with an increased likelihood of depressive symptoms. However, these contemporaneous associations were explained by adjustment for detailed measures of socioeconomic circumstances and physical activity. In prospective analyses, lower scores on the healthy dietary pattern and higher scores on the unhealthy dietary pattern independently predicted increased depressive symptoms across time, before and after adjustment for potential confounders and baseline depressive symptoms, but only for those in the oldest cohort. Dietary patterns did not explain the relationship between socioeconomic position and depressive symptoms. Conclusion The results of this study confirm that the relationship between habitual dietary intake and depressive symptoms is somewhat explained by socioeconomic circumstances and other health behaviours, but suggest that long term exposure to unhealthy dietary habits independently predisposes to depression over the lifecourse.

Hemispheric interactions are different in left-handed individuals

In a previous study, N. Cherbuin and C. Brinkman (2006) showed that in right-handed participants, interhemispheric transfer time (measured with A. T. Poffenbergers, 1912, paradigm) was a significant predictor of the efficiency of hemispheric interactions (measured with a split visual field, letter-matching task). No effect was found for degree of handedness in this study. This was surprising because handedness has been shown to be associated with differences in the morphology and the structure of the corpus callosum, and cerebral anatomical lateralization, as well as functional lateralization both in behavioral and scanning studies. Because these findings were found in a large sample, but one limited to right-handed participants, the aim of the present study was to determine whether a similar relationship was present between interhemispheric transfer time and hemispheric interaction in left-handed participants (using identical measures) and to assess whether the analysis of a larger sample that comprised both left- and right-handed participants might reveal an effect of handedness. Results demonstrate significant handedness effects, suggesting that left-handed individuals tend to have more efficient hemispheric interactions.