Association between ultra-processed foods and recurrence of depressive symptoms: the Whitehall II cohort study.

OBJECTIVES: To examine the association between high intakes of ultra-processed foods (UPF) and recurrence of depressive symptoms (DepS) in a Western non-Mediterranean country and its contribution to the overall diet-depression relationship. METHODS: Analyses were carried out on British participants from the Whitehall II cohort. Present analyses were restricted to white participants N = 4554 (74% men, mean age = 61; SD = 5.9). UPF consumption was estimated from a 127-item food frequency questionnaire using the NOVA classification, and cumulative average of UPF intakes (g/day) over 11 years of exposure (1991/1994-2002/2004) was computed. Recurrent DepS after measurement of UPF was defined as having two or more episodes of DepS (the Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16 or antidepressants use) during four phases of follow-up (2002/2004-2015/2016). RESULTS: Over the follow-up, 588 (12.9%) cases of recurrent DepS were observed. After adjusting for socio-demographic factors, health behaviours and health status, participants in top quintile of UPF intakes [mean 33% of total daily intakes in grams] had 31% higher odds of recurrent DepS (odds ratio 1.31; 95% CI 1.04-1.64) compared to participants in the four lowest quintiles of UPF [mean 18.1% of total daily intakes in grams]. Additional analyses showed that associations between adherence to several diet quality measures and recurrent DepS were partially attenuated (17-27%) by UPF intakes. CONCLUSION: In this British population, high intakes of ultra-processed foods were associated with increased odds of recurrent depressive symptoms and contributed to the overall diet quality-depressive symptoms association.

Diet and depression: exploring the biological mechanisms of action.

The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression onset and symptom management. To guide future clinical trials and targeted dietary therapies, this review provides an overview of what is currently known regarding underlying mechanisms of action by which diet may influence mental and brain health. The mechanisms of action associating diet with health outcomes are complex, multifaceted, interacting, and not restricted to any one biological pathway. Numerous pathways were identified through which diet could plausibly affect mental health. These include modulation of pathways involved in inflammation, oxidative stress, epigenetics, mitochondrial dysfunction, the gut microbiota, tryptophan-kynurenine metabolism, the HPA axis, neurogenesis and BDNF, epigenetics, and obesity. However, the nascent nature of the nutritional psychiatry field to date means that the existing literature identified in this review is largely comprised of preclinical animal studies. To fully identify and elucidate complex mechanisms of action, intervention studies that assess markers related to these pathways within clinically diagnosed human populations are needed.

Associations between exploratory dietary patterns and incident type 2 diabetes: a federated meta-analysis of individual participant data from 25 cohort studies.

PURPOSE: In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world. METHODS: This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis. RESULTS: 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRRpooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I2 = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRRpooled per 1 SD = 1.057, 95% CI 1.027-1.088). CONCLUSION: Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed.

Associations of Total Legume, Pulse, and Soy Consumption with Incident Type 2 Diabetes: Federated Meta-Analysis of 27 Studies from Diverse World Regions.

BACKGROUND: The consumption of legumes is promoted as part of a healthy diet in many countries but associations of total and types of legume consumption with type 2 diabetes (T2D) are not well established. Analyses across diverse populations are lacking despite the availability of unpublished legume consumption data in prospective cohort studies. OBJECTIVE: To examine the prospective associations of total and types of legume intake with the risk of incident T2D. METHODS: Meta-analyses of associations between total legume, pulse, and soy consumption and T2D were conducted using a federated approach without physical data-pooling. Prospective cohorts were included if legume exposure and T2D outcome data were available and the cohort investigators agreed to participate. We estimated incidence rate ratios (IRRs) and CIs of associations using individual participant data including ≤42,473 incident cases among 807,785 adults without diabetes in 27 cohorts across the Americas, Eastern Mediterranean, Europe, and Western Pacific. Random-effects meta-analysis was used to combine effect estimates and estimate heterogeneity. RESULTS: Median total legume intake ranged from 0-140 g/d across cohorts. We observed a weak positive association between total legume consumption and T2D (IRR = 1.02, 95% CI: 1.01 to 1.04) per 20 g/d higher intake, with moderately high heterogeneity (I2 = 74%). Analysis by region showed no evidence of associations in the Americas, Eastern Mediterranean, and Western Pacific. The positive association in Europe (IRR = 1.05, 95% CI: 1.01 to 1.10, I2 = 82%) was mainly driven by studies from Germany, UK, and Sweden. No evidence of associations was observed for the consumption of pulses or soy. CONCLUSIONS: These findings suggest no evidence of an association of legume intakes with T2D in several world regions. The positive association observed in some European studies warrants further investigation relating to overall dietary contexts in which legumes are consumed, including accompanying foods which may be positively associated with T2D.

Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies.

With depression being the psychiatric disorder incurring the largest societal costs in developed countries, there is a need to gather evidence on the role of nutrition in depression, to help develop recommendations and guide future psychiatric health care. The aim of this systematic review was to synthesize the link between diet quality, measured using a range of predefined indices, and depressive outcomes. Medline, Embase and PsychInfo were searched up to 31st May 2018 for studies that examined adherence to a healthy diet in relation to depressive symptoms or clinical depression. Where possible, estimates were pooled using random effect meta-analysis with stratification by observational study design and dietary score. A total of 20 longitudinal and 21 cross-sectional studies were included. These studies utilized an array of dietary measures, including: different measures of adherence to the Mediterranean diet, the Healthy Eating Index (HEI) and Alternative HEI (AHEI), the Dietary Approaches to Stop Hypertension, and the Dietary Inflammatory Index. The most compelling evidence was found for the Mediterranean diet and incident depression, with a combined relative risk estimate of highest vs. lowest adherence category from four longitudinal studies of 0.67 (95% CI 0.55-0.82). A lower Dietary Inflammatory Index was also associated with lower depression incidence in four longitudinal studies (relative risk 0.76; 95% CI: 0.63-0.92). There were fewer longitudinal studies using other indices, but they and cross-sectional evidence also suggest an inverse association between healthy diet and depression (e.g., relative risk 0.65; 95% CI 0.50-0.84 for HEI/AHEI). To conclude, adhering to a healthy diet, in particular a traditional Mediterranean diet, or avoiding a pro-inflammatory diet appears to confer some protection against depression in observational studies. This provides a reasonable evidence base to assess the role of dietary interventions to prevent depression. This systematic review was registered in the PROSPERO International Prospective Register of Systematic Reviews under the number CRD42017080579.

Correction: Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies.

This article was originally published under standard licence, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.

Associations between long-term adherence to healthy diet and recurrent depressive symptoms in Whitehall II Study.

PURPOSE: We examined whether long-term adherence to three diet quality scores-the Alternative Healthy Eating Index-2010 (AHEI-2010), Dietary Approach to Stop Hypertension (DASH) and  transformed-Mediterranean Diet Score (tMDS), Alternative Healthy Eating Index-2010 (AHEI-2010) and Dietary Approach to Stop Hypertension (DASH) is associated with the risk of recurrent depressive symptoms. METHODS: Analyses were conducted on a sample of 4949 men and women from the Whitehall II study. Diet scores were calculated using data collected from food frequency questionnaires repeated over 11 years of exposure (1991/1993-2002/2004). Recurrence of depressive symptoms was defined when participants reported at least two episodes of depressive symptoms (assessed by Center for Epidemiologic Studies Depression Scale and use of antidepressants) over the four phases of follow-up (2002/04-2015/16). RESULTS: After adjustment for potential cofounders, higher scores on AHEI-2010, DASH and tMDS at the end of the exposure period were associated with lower risk of recurrent depressive symptoms over the 13-year follow-up. Repeat measures of dietary history showed that participants who maintained a high AHEI-2010 score over the 11-year exposure period had a 19% (OR 0.81, 95% CI 0.65-1.00) lower odds of recurrent depressive symptoms compared to those who maintained a low AHEI score. Participants whose AHEI-2010 score decreased over time had a 1.34-fold increased odds (95% CI 1.02-1.75) of developing recurrent depressive symptoms compared to those maintaining a high AHEI-2010. No robust associations were observed for long-term tMDS and DASH. CONCLUSION: Our findings suggest that long-term adherence to healthy diet defined by Alternative Healthy Eating Index-2010 confers protection against recurrent depressive symptoms.

Association of Midlife Diet With Subsequent Risk for Dementia.

Importance: Observational studies suggest that diet is linked to cognitive health. However, the duration of follow-up in many studies is not sufficient to take into account the long preclinical phase of dementia, and the evidence from interventional studies is not conclusive. Objective: To examine whether midlife diet is associated with subsequent risk for dementia. Design, Setting, and Participants: Population-based cohort study established in 1985-1988 that had dietary intake assessed in 1991-1993, 1997-1999, and 2002-2004 and follow-up for incident dementia until March 31, 2017. Exposures: Food frequency questionnaire to derive the Alternate Healthy Eating Index (AHEI), an 11-component diet quality score (score range, 0-110), with higher scores indicating a healthier diet. Main Outcome and Measures: Incident dementia ascertained through linkage to electronic health records. Results: Among 8225 participants without dementia in 1991-1993 (mean age, 50.2 years [SD, 6.1 years]; 5686 [69.1%] were men), a total of 344 cases of incident dementia were recorded during a median follow-up of 24.8 years (interquartile range, 24.2-25.1 years). No significant difference in the incidence rate for dementia was observed in tertiles of AHEI exposure during 1991-1993, 1997-1999 (median follow-up, 19.1 years), and 2002-2004 (median follow-up, 13.5 years). Compared with an incidence rate for dementia of 1.76 (95% CI, 1.47-2.12) per 1000 person-years in the worst tertile of AHEI (lowest tertile of diet quality) in 1991-1993, the absolute rate difference for the intermediate tertile was 0.03 (95% CI, -0.43 to 0.49) per 1000 person-years and for the best tertile was 0.04 (95% CI, -0.42 to 0.51) per 1000 person-years. Compared with the worst AHEI tertile in 1997-1999 (incidence rate for dementia, 2.06 [95% CI, 1.62 to 2.61] per 1000 person-years), the absolute rate difference for the intermediate AHEI tertile was 0.14 (95% CI, -0.58 to 0.86) per 1000 person-years and for the best AHEI tertile was 0.14 (95% CI, -0.58 to 0.85) per 1000 person-years. Compared with the worst AHEI tertile in 2002-2004 (incidence rate for dementia, 3.12 [95% CI, 2.49 to 3.92] per 1000 person-years), the absolute rate difference for the intermediate AHEI tertile was -0.61 (95% CI, -1.56 to 0.33) per 1000 person-years and for the best AHEI tertile was -0.73 (95% CI, -1.67 to 0.22) per 1000 person-years. In the multivariable analysis, the adjusted hazard ratios (HRs) for dementia per 1-SD (10-point) AHEI increment were not significant as assessed in 1991-1993 (adjusted HR, 0.97 [95% CI, 0.87 to 1.08]), in 1997-1999 (adjusted HR, 0.97 [95% CI, 0.83 to 1.12]), or in 2002-2004 (adjusted HR, 0.87 [95% CI, 0.75 to 1.00]). Conclusions and Relevance: In this long-term prospective cohort study, diet quality assessed during midlife was not significantly associated with subsequent risk for dementia.

High-Sugar, High-Saturated-Fat Dietary Patterns Are Not Associated with Depressive Symptoms in Middle-Aged Adults in a Prospective Study.

Background: The consumption of unhealthy "Western" dietary patterns has been previously associated with depressive symptoms in different populations. Objective: We examined whether high-sugar and high-saturated-fat dietary patterns are associated with depressive symptoms over 5 y in a British cohort of men and women. Methods: We used data from the Whitehall II study in 5044 individuals (aged 35-55 y). Diet was assessed at phase 7 (2003-2004) using a validated food-frequency questionnaire. Dietary patterns were derived by using reduced rank regression with sugar, saturated fat, and total fat as response variables. The Center for Epidemiological Studies-Depression (CES-D) scale was used to assess depressive symptoms (CES-D sum score ≥16 and/or use of antidepressant medication) at phase 7 and at phase 9 (2008-2009). We applied logistic regression analyses to test the association between dietary patterns and depressive symptoms. All analyses were stratified by sex. Results: In total, 398 cases of recurrent and 295 cases of incident depressive symptoms were observed. We identified 2 dietary patterns: a combined high-sugar and high-saturated-fat (HSHF) and a high-sugar dietary pattern. No association was observed between the dietary patterns and either incidence of or recurrent depressive symptoms in men or women. For example, higher consumption of the HSHF dietary pattern was not associated with recurrent depressive symptoms in men (model 3, quartile 4: OR: 0.67; 95% CI: 0.36, 1.23; P-trend = 0.13) or in women (model 3, quartile 4: OR: 1.26; 95% CI: 0.58, 2.77; P-trend = 0.97). Conclusion: Among middle-aged men and women living in the United Kingdom, dietary patterns containing high amounts of sugar and saturated fat are not associated with new onset or recurrence of depressive symptoms.

The Inflammatory Potential of the Diet at Midlife Is Associated with Later Healthy Aging in French Adults.

Background: While low-grade chronic inflammation has been suggested as a major modulator of healthy aging (HA), no study has yet investigated the link between the inflammatory potential of the diet and multidimensional concepts of HA. Objective: We aimed to evaluate the association between the inflammatory potential of the diet at midlife, as measured by the Dietary Inflammatory Index (DII), and HA assessed 13 y later. Methods: We analyzed data from 2796 participants in the French Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) study aged 45-60 y at baseline (1994-1995) and initially free of diabetes, cardiovascular disease, and cancer. During the trial phase of the study (1994-2002), participants received either a placebo or a daily nutritional dose of antioxidant supplement (120 mg vitamin C, 6 mg ß-carotene, 30 mg vitamin E, 100 µg Se, 20 mg Zn). HA was assessed in 2007-2009, and defined as having no major chronic disease, good physical and cognitive functioning, independence in daily activities, no depressive symptoms, good social health, good overall self-perceived health, and no function-limiting pain. The DII was calculated based on repeated baseline 24-h dietary records. Its association with HA was assessed by robust-error-variance Poisson regression, providing RR estimates. Results: After adjustment for potential confounders, higher DII scores (reflecting a more proinflammatory diet), were associated with a decreased likelihood of HA: RRtertile 3/tertile 1 = 0.85 (95% CI: 0.74, 0.99); P-trend = 0.03. Secondary analyses revealed that this association was only significant among participants who had been in the placebo group during the trial phase: RRtertile 3/tertile 1 = 0.80 (95% CI: 0.64, 1.00); P-trend = 0.04. Conclusions: This study suggests that a proinflammatory diet may lower the probability of overall HA. The SU.VI.MAX trial was registered at www.clinicaltrials.gov as NCT00272428.

Alternative Healthy Eating Index 2010, Dietary Inflammatory Index and risk of mortality: results from the Whitehall II cohort study and meta-analysis of previous Dietary Inflammatory Index and mortality studies.

We aimed to examine the association between the Alternative Healthy Eating Index updated in 2010 (AHEI-2010), the Dietary Inflammatory Index (DIITM) and risk of mortality in the Whitehall II study. We also conducted a meta-analysis on the DII-based results from previous studies to summarise the overall evidence. Data on dietary behaviour assessed by self-administered repeated FFQ and on mortality status were available for 7627 participants from the Whitehall II cohort. Cox proportional hazards regression models were performed to assess the association between cumulative average of AHEI-2010 and DII scores and mortality risk. During 22 years of follow-up, 1001 participants died (450 from cancer, 264 from CVD). Both AHEI-2010 (mean=48·7 (sd 10·0)) and DII (mean=0·37 (sd 1·41)) were associated with all-cause mortality. The fully adjusted hazard ratio (HR) per sd, were 0·82; 95 % CI 0·76, 0·88 for AHEI-2010 and 1·18; 95 % CI 1·08, 1·29 for DII. Significant associations were also observed with cardiovascular and cancer mortality risk. For DII, a meta-analysis (using fixed effects) from this and four previous studies showed a positive association of DII score with all-cause (HR=1·04; 95 % CI 1·03, 1·05, 28 891deaths), cardiovascular (HR=1·05; 95 % CI 1·03, 1·07, 10 424 deaths) and cancer mortality (HR=1·05; 95 % CI 1·03, 1·07, n 8269).The present study confirms the validity to assess overall diet through AHEI-2010 and DII in the Whitehall II cohort and highlights the importance of considering diet indices related to inflammation when evaluating all-cause, cardiovascular and cancer mortality risk.

Working memory performance is related to intrinsic resting state functional connectivity changes in community-dwelling elderly cohort.

Characterization of normal age-related changes in resting state brain networks associated with working memory performance is a major prerequisite for studying neurodegenerative diseases. The aim of this study was to investigate the relationship between performing a working memory task (under MRI) and resting-state brain networks in a large cohort of healthy elderly subjects (n=337). Functional connectivity and interactions between networks were assessed within the default mode (DMN), salience (SN), and right and left central executive (CEN) networks in two groups of subjects classed by their performance (low and high). The low performance group showed lower functional connectivity in both the DMN and SN, and higher functional connectivity in the right and left CEN compared to the high performance group. Overall the functional connectivity within the DMN and the CEN were correlated. The lower functional connectivity within the DMN and SN in the low performance group is suggestive of altered attentional and memory processes and/or altered motivation. The higher functional connectivity within the CEN could be related to compensatory mechanisms, without which the subjects would have even lower performances. The correlation between the DMN and CEN suggests a modulation between the lower functional connectivity within the DMN and the higher functional connectivity within the CEN when performance is reduced. Finally, this study suggests that performance modifications in healthy elderly subjects are associated with reorganization of functional connectivity within the DMN, SN, and CEN.

Age trajectories of glycaemic traits in non-diabetic South Asian and white individuals: the Whitehall II cohort study.

AIMS/HYPOTHESIS: South Asian individuals have an increased prevalence of type 2 diabetes, but little is known about the development of glycaemic traits in this ethnic group. We compared age-related changes in glycaemic traits between non-diabetic South Asian and white participants. METHODS: In a prospective British occupational cohort with 5-yearly clinical examinations (n = 230/5,749 South Asian/white participants, age 39-79 years at baseline), age-related trajectories of fasting glucose (FG) and 2 h post-load glucose (PLG), log-transformed fasting insulin (FINS) and 2 h post-load insulin (PLINS), HOMA insulin sensitivity (HOMA2-%S) and HOMA insulin secretion (HOMA2-%B) were fitted for South Asian and white individuals who remained free of diabetes between 1991 and 2009. RESULTS: In sex-adjusted multilevel models, FG was stable in white participants but increased with age in South Asians (0.12 [SE = 0.04] mmol/l per decade). PLG, FINS and PLINS levels were lower among white participants (by 0.271 [SE = 0.092] mmol/l, 0.306 [SE = 0.046] log pmol/l, 0.707 [SE = 0.059] log pmol/l at age 50, respectively) compared with South Asians, although their age-related trajectories were parallel. HOMA2-%S was higher (0.226 [SE = 0.038] at age 50) and HOMA2-%B lower (by 0.189 [SE = 0.026] at age 50) among white than South Asian participants. The age-related decline in HOMA2-%S was similar in these groups, but the age-related increase in HOMA2-%B was greater in white participants (0.04 [SE = 0.02] per decade). This difference was explained by obesity, lifestyle and social status. CONCLUSIONS/INTERPRETATION: Findings from a diabetes-free population suggest an inadequate pancreatic beta cell reserve in South Asians, as a significantly steeper age-related increase in FG was observed in this ethnic group compared with white individuals.

Working memory activation of neural networks in the elderly as a function of information processing phase and task complexity.

Changes in working memory are sensitive indicators of both normal and pathological brain aging and associated disability. The present study aims to further understanding of working memory in normal aging using a large cohort of healthy elderly in order to examine three separate phases of information processing in relation to changes in task load activation. Using covariance analysis, increasing and decreasing neural activation was observed on fMRI in response to a delayed item recognition task in 337 cognitively healthy elderly persons as part of the CRESCENDO (Cognitive REServe and Clinical ENDOphenotypes) study. During three phases of the task (stimulation, retention, probe), increased activation was observed with increasing task load in bilateral regions of the prefrontal cortex, parietal lobule, cingulate gyrus, insula and in deep gray matter nuclei, suggesting an involvement of central executive and salience networks. Decreased activation associated with increasing task load was observed during the stimulation phase, in bilateral temporal cortex, parietal lobule, cingulate gyrus and prefrontal cortex. This spatial distribution of decreased activation is suggestive of the default mode network. These findings support the hypothesis of an increased activation in salience and central executive networks and a decreased activation in default mode network concomitant to increasing task load.

Sleep complaints and metabolic syndrome in an elderly population: the Three-City Study.

OBJECTIVES: To assess whether sleep complaints (rather than clinically defined sleep disturbances) were associated with the metabolic syndrome (MetS) and each of its components in an elderly population. METHODS: Cross-sectional analyses of data from the French Three City Study, a large multicenter cohort of elderly community-dwellers. PARTICIPANTS: 6,354 participants (56.4% women, median age 73; range: 65-97 years). MEASUREMENTS: Frequency of insomnia complaints (difficulty in initiating sleep, difficulty in maintaining sleep [DMS], and early morning awakening) and excessive daytime sleepiness (EDS) were self-reported. MetS was assessed using National Cholesterol Education program Adult Treatment Panel III criteria. RESULTS: A total of 977 participants had MetS. After adjustment for a large range of potential confounders, we report an association between the number of insomnia complaints and MetS. Among insomnia complaints only DMS was consistently associated with MetS (OR: 1.23, 95% CI: 1.06 to 1.43). Our results showed that EDS independently increased the risk of MetS (OR: 1.46, 95% CI: 1.18 to 1.81 for "frequently"; OR: 1.99, 95% CI: 1.49 to 1.67 for "often"). The EDS-MetS association was independent of past-history of cardiovascular disease, insomnia complaints, and obesity and loud snoring. CONCLUSION: We report significant independent associations between frequent sleep complaints (EDS and to a lesser extent DMS) and MetS in the elderly with potential implications in terms of management and cardiovascular prevention in general geriatric practice. Prospective studies are required to clarify the direction of the association between sleep complaints and MetS.

Education modulates the impact of white matter lesions on the risk of mild cognitive impairment and dementia.

OBJECTIVES: Conflicting results have been reported regarding the association between white matter lesions (WML) and cognitive impairment. We hypothesized that education, a marker of cognitive reserve (CR), could modulate the effects of WML on the risk of mild cognitive impairment (MCI) or dementia. METHODS: We followed 500 healthy subjects from a cohort of community-dwelling persons aged 65 years and over (ESPRIT Project). At baseline, WML volume was measured using a semi-automatic method on T2-weighted MRI. Standardized cognitive and neurological evaluations were repeated after 2, 4, and 7 years. The sample was dichotomized according to education level into low (≤8 years) and high (>8 years) education groups. Cox proportional hazard models were constructed to study the association between WML and risk of MCI/dementia. RESULTS: The interaction between education level and WML volume reached significance (p = 0.017). After adjustment for potential confounders, the association between severe WML and increased MCI/dementia risk was significant in the low education group (≤8 years) (p = 0.02, hazard ratio [HR]: 3.77 [1.29-10.99]), but not in the high education group (>8 years) (p = 0.82, HR: 1.07 [0.61-1.87]). CONCLUSIONS: Severe WML significantly increases the risk of developing MCI/dementia over a 7-year period in low educated participants. Subjects with higher education levels were seen to be more likely to be resilient to the deleterious effects of severe WML. The CR hypothesis suggests several avenues for dementia prevention.

APOE ε4 and risk for Alzheimer's disease: do regionally distributed white matter hyperintensities play a role?

BACKGROUND: We previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase the risk for Alzheimer's disease (AD). Here, we examined whether individuals with apolipoprotein E gene (APOE ε4) have increased parietal WMH volume. METHODS: Participants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n = 694, 47 with dementia) in northern Manhattan and the Etude Santé Psychologique Prévalence Risques et Traitement study (ESPRIT; n = 539, 8 with dementia) in Montpellier. The association between regional WMH and APOE ε4 was examined separately in each group and then in a combined analysis. RESULTS: In WHICAP, ε4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, ε4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, ε4 carriers had higher WMH in parietal and occipital lobes. Increased WMH volume was associated with increased frequency of dementia irrespective of APOE ε4 status; those with the ε4 were more likely to have dementia if they also had increased parietal WMH. CONCLUSIONS: APOE ε4 is associated with increased parietal lobe WMH.