Dietary Glycemic Load and Plasma Amyloid-β Biomarkers of Alzheimer's Disease

Previous studies have highlighted links between a high-glycemic-load (GL) diet and Alzheimer's disease in apolipoprotein E ε4 (APOE4) carriers. However, the impact of high-GL diet on plasma amyloid-β (Aβ), an Alzheimer's disease hallmark that can be detected decades before clinical symptomatology, is unknown. This study examined the association between plasma Aβ peptides (Aβ(40), Aβ(42) concentration and Aβ(42)/Aβ(40) ratio) and GL. The influence of the GL of four meal types (breakfast, lunch, afternoon snack, and dinner) was also determined. From the prospective Three-City study, 377 participants with plasma Aβ measurements, and who completed the Food Frequency Questionnaire, were selected. The association between plasma Aβ and GL was tested using an adjusted linear regression model. Lunch GL was associated with a lower plasma Aβ(42) concentration (β = -2.2 [CI = -4.27, -0.12], p = 0.038) and lower Aβ(42)/Aβ(40) ratio (β = -0.009 [CI = -0.0172, -0.0007], p = 0.034) in the model adjusted for center, age, sex, education level, APOE4 status, energy intake, serum creatinine, total cholesterol, and Mediterranean-like diet. No significant association was found with the GL of the other meal types. These results suggest that dietary GL may independently modulate the plasma Aβ of the APOE4 status. The mechanism underlying diet, metabolic response, and Aβ peptide regulation must be elucidated

Spatial distribution of cerebral white matter lesions predicts progression to mild cognitive impairment and dementia

CONTEXT White matter lesions (WML) increase the risk of dementia. The relevance of WML location is less clear. We sought to determine whether a particular WML profile, based on the density and location of lesions, could be associated with an increased risk of mild cognitive impairment (MCI) or dementia over the following 7 years. METHODS In 426 healthy subjects from a cohort of community-dwelling people aged 65 years and over (ESPRIT Project), standardized cognitive and neurological evaluations were repeated after 2, 4 and 7 years. Patterns of WML were computed with a supervised data mining approach (decision trees) using the regional WML volumes (frontal, parietal, temporal, and occipital regions) and the total WML volume estimated at baseline. Cox proportional hazard models were then constructed to study the association between WML patterns and risk of MCI/dementia. RESULTS Total WML volume and percentage of WML in the temporal region proved to be the best predictors of progression to MCI and dementia. Specifically, severe total WML load with a high proportion of lesions in the temporal region was significantly associated with the risk of developing MCI or dementia. CONCLUSIONS Above a certain threshold of damage, a pattern of WML clustering in the temporal region identifies individuals at increased risk of MCI or dementia. As this WML pattern is observed before the onset of clinical symptoms, it may facilitate the detection of patients at risk of MCI/dementia.The ESPRIT Project is financed by the regional government of Languedoc-Roussillon (http://www.laregion.fr), the Agence Nationale de la Recherche (ANR: http://www.agence-nationale-recherche.fr) and an unconditional grant from Novartis (http://www.novartis.fr). This study is also supported by France Alzheimer (http://www.francealzheimer.org/)

Cerebral white matter hyperintensities in the prediction of cognitive decline and incident dementia.

International audienceAbstract Cerebral white matter hyperintensities (WMH), detected in vivo with magnetic resonance imaging (MRI), are commonly used to assess cerebrovascular burden in cognitive impairment. However, the association between WMH and cognition is not consistent across the literature. The present review examines evidence from published longitudinal studies. We reviewed the PubMed data base from January 1990 to March 2013 and included studies investigating the association of WMH with (1) the risk of dementia in the general population, (2) the risk of conversion to dementia in the mild cognitive impairment (MCI) population, and (3) cognitive decline in the general population. WMH were associated with all types of dementia in the general population, but not in MCI patients. Results are discrepant for global decline. WMH appear to be early predictors of the risk of dementia, but this association appears to be modulated by cognitive reserve, age and the spatial distribution of lesions. There are, however, some limits in the use of WMH as a marker of vascular burden. In addition to their ischaemic origin, WMH may be the result of co-occurring morbidity. Further research is needed to elucidate to what extent WMH actually reflect vascular risk to evaluate the likely efficacy of interventions specifically targeting WMH reduction

White Matter Hyperintensities as Early and Independent Predictors of Alzheimer's Disease Risk

International audienceThere is growing evidence that vascular health plays a significant role in the etiology of clinical Alzheimer's disease (AD). Understanding the timing of vascular changes in relation to progression from cognitive impairment to AD has become of increasing importance, being both possible pre-clinical markers and potentially modifiable risk factors. White matter hyperintensities (WMH) detected in vivo with magnetic resonance imaging, are commonly used to assess cerebrovascular burden in cognitive impairment and appear to be associated with an increased risk of cognitive decline due to many causes. The present review examines specifically the association between WMH and AD and its related biomarkers. Overall, current findings across the literature suggest that WMH may predict AD at least a decade before the clinical stage of the disease, independently of biomarkers of AD pathology, thus indicating that vascular factors may constitute important targets for pre-clinical detection and intervention

[Epidemiology of mental diseases in the elderly]

International audiencen.

Hostility has both positive and negative associations with cognition in old age: results from the ESPRIT study: Hostility and cognition in old age

Background: Chronic psychological stress has been associated with cognitive decline and dementia. The aim of this study is to determine if the endogenous stressors hostility and anger are related to cognitive performance and decline over time in the elderly. Methods: 1252 participants in a population based cohort from Montpellier France, completed the Buss-Durkee Hostility Inventory and Speilberger State Trait Anger Expression Inventory. They also were tested using the Benton Visual Retention Test, the Isaacs Set test of category fluency and Trails A and B at the same time point and 2 and 4 years later. Mixed models were used to examine the association between hostility and anger factor scores and cognitive function. Results: In men, after adjusting for age, education, depression, coronary heart disease, smoking and body mass index there were significant associations between Guilt and Suspicion and State Anger and cognitive performance. The only significant time by hostility factor interaction was for the association between State Anger and Trails A. In women, after adjustments the associations between Trait Anger and Anger-Out and Isaacs Set Test and Verbal and Physical Aggression and Guilt and Trails A were significant, and there were no significant time by hostility interactions. Conclusions: Expressed hostility had positive associations and suppressed hostility tended to have negative associations with level of cognitive function, but not with cognitive decline in old age. This suggests that personality may impact across the lifespan on cognitive function

Revised Criteria for Mild Cognitive Impairment: Validation within a Longitudinal Population Study.

Background: Mild cognitive impairment (MCI) refers to the transitional zone between normal ageing and dementia. Current criteria perform poorly within the general population setting. Revisions have been proposed based on results obtained from clinical and epidemiological studies. Objective: To evaluate revised diagnostic criteria for mild cognitive impairment (MCI-R) incorporating changes in activity level and non-mnesic cognitive functioning. Method: MCI-R subjects were recruited from a representative network of general practitioners in the south of France. A computerized neuropsychometric examination was given. At 2 years of follow-up, a diagnosis of dementia was made by a neurologist using DSM-IIIR criteria and without knowledge of the results of the cognitive testing. Rates of conversion to incident dementia were assessed by receiver operating characteristics analysis. Results: The MCI-R prevalence was found to be 16.6% using revised criteria. A significantly better prediction of transition to dementia (AUC = 0.80, sensitivity: 95%, specificity: 66%) was obtained with MCI-R than with the previous MCI criteria (AUC = 0.48, sensitivity: 5%, specificity: 91%). The predictive power was found to increase when MCI subtypes were combined. Conclusion: Incorporating the possibility of change in activity level and alteration of non-mnesic cognitive functions have been found to ameliorate the original algorithm and better define subjects converting to dementia. This definition may be applicable to both clinical and population research. Copyright (c) 2006 S. Karger AG, Basel

Framing the impact of physical pain on suicide attempts. A reply to Stubbs

International audienc

A meta-analysis of cytokines in suicidal behavior

International audienceBACKGROUND:We conducted the first meta-analysis of studies comparing the plasma and CSF concentrations of cytokines in suicidal patients vs. non-suicidal patients or healthy controls.METHODS:We searched Medline, Web of Science, and PsycINFO from 1965 to November 2014 for relevant studies. Manual searches of references and unpublished data were also included. Suicidal patients included severe suicide ideators and suicide attempters.RESULTS:Eleven articles were available for the meta-analysis, for a total sample size of 494 suicidal patients, 497 non-suicidal patients and 398 healthy controls. Levels of 6 independent plasma cytokines (IL2, IL6, TNFalpha, IFNgamma, IL4, TGFbeta) were meta-analyzed for plasma studies comparing suicidal vs. both controls. IL8 level was meta-analyzed for cerebrospinal fluid studies comparing suicidal patients with healthy controls. We reported with medium effect size, that suicidal patients had: (1) lower IL2 plasma levels than both non-suicidal patients and healthy controls (medium effect size); (2) lower IL4 and higher TGFbeta plasma levels than healthy controls.CONCLUSION:Our results promote the hypothesis of altered inflammatory markers in suicidal patients, for both pro-inflammatory (IL2) and anti-inflammatory (IL4 and TGFbeta) cytokines