Ambient Air Pollution Exposure and Cerebral White Matter Hyperintensities in Older Adults: A Cross-Sectional Analysis in the Three-City Montpellier Study.

BACKGROUND: Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive health, and this could be related to the effect of air pollution on vascular health. OBJECTIVE: We aim to evaluate the association between air pollution exposure and a magnetic resonance imaging (MRI) marker of cerebral vascular burden, white matter hyperintensities (WMH). METHODS: This cross-sectional analysis used data from the French Three-City Montpellier study. Randomly selected participants 65-80 years of age underwent an MRI examination to estimate their total and regional cerebral WMH volumes. Exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) at the participants' residential address during the 5 years before the MRI examination was estimated with land use regression models. Multinomial and binomial logistic regression assessed the associations between exposure to each of the three pollutants and categories of total and lobar WMH volumes. RESULTS: Participants' (n=582) median age at MRI was 70.7 years [interquartile range (IQR): 6.1], and 52% (n=300) were women. Median exposure to air pollution over the 5 years before MRI acquisition was 24.3 (IQR: 1.7) µg/m3 for PM2.5, 48.9 (14.6) µg/m3 for NO2, and 2.66 (0.60) 10-5/m for BC. We found no significant association between exposure to the three air pollutants and total WMH volume. We found that PM2.5 exposure was significantly associated with higher risk of temporal lobe WMH burden [odds ratio (OR) for an IQR increase=1.82 (95% confidence interval: 1.41, 2.36) for the second volume tercile, 2.04 (1.59, 2.61) for the third volume tercile, reference: first volume tercile]. Associations for other regional WMH volumes were inconsistent. CONCLUSION: In this population-based study in older adults, PM2.5 exposure was associated with increased risk of high WMH volume in the temporal lobe, strengthening the evidence on PM2.5 adverse effect on the brain. Further studies looking at different markers of cerebrovascular damage are still needed to document the potential vascular effects of air pollution. https://doi.org/10.1289/EHP12231.

Is Hippocampal Volume a Relevant Early Marker of Dementia?

OBJECTIVE: Hippocampal volume (HV) is a key imaging marker to improve Alzheimer's disease risk prediction. However, longitudinal studies are rare, and hippocampus may also be implicated in the subtle aging-related cognitive decline observed in dementia-free individuals. Our aim was to determine whether HV, measured by manual or automatic segmentation, is associated with dementia risk and cognitive decline in participants with and without incident dementia. METHODS: At baseline, 510 dementia-free participants from the French longitudinal ESPRIT cohort underwent magnetic resonance imaging. HV was measured by manual and by automatic segmentation (FreeSurfer 6.0). The presence of dementia and cognitive functions were investigated at each follow-up (2, 4, 7, 10, 12, and 15 years). Cox proportional hazards models and linear mixed models were used to assess the association of HV with dementia risk and with cognitive decline, respectively. RESULTS: During the 15-years follow-up, 42 participants developed dementia. Reduced HV (regardless of the measurement method) was significantly associated with higher dementia risk and cognitive decline in the whole sample. However, only the automatically measured HV was associated with cognitive decline in dementia-free participants. CONCLUSION: These results suggest that HV can be used to predict the long-term risk of dementia but also cognitive decline in a dementia-free population. This raises the question of the relevance of HV measurement as an early marker of dementia in the general population.

Glucometabolic Changes Are Associated with Structural Gray Matter Alterations in Prodromal Dementia.

BACKGROUND: Glucometabolic changes, such as high glycemic load (GL) diet and insulin resistance (IR), are potential risk factor of Alzheimer's disease (AD). Yet, the effect of these factors on brain alterations that contribute to AD pathology has not been clearly demonstrated. OBJECTIVE: We aimed to assess the relationship of GL and IR with gray matter volumes involved in prodromal dementia. METHODS: GL and Triglyceride-Glucose (TyG) index, an IR surrogate marker, were calculated in 497 participants who underwent magnetic resonance imaging (MRI). The gray matter volumes most related to prodromal dementia/mild cognitive impairment (diagnosed in 18/158 participants during the 7-year follow-up) were identified using a data-driven machine learning algorithm. RESULTS: Higher GL diet was associated with reduced amygdala volume. The TyG index was negatively associated with the hippocampus, amygdala, and putamen volumes. CONCLUSION: These results suggest that GL and IR are associated with lower gray matter volumes in brain regions involved in AD pathology.

Dietary Glycemic Load and Plasma Amyloid-ß 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-ß (Aß), an Alzheimer's disease hallmark that can be detected decades before clinical symptomatology, is unknown. This study examined the association between plasma Aß peptides (Aß40, Aß42 concentration and Aß42/Aß40 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 Aß measurements, and who completed the Food Frequency Questionnaire, were selected. The association between plasma Aß and GL was tested using an adjusted linear regression model. Lunch GL was associated with a lower plasma Aß42 concentration (ß = -2.2 [CI = -4.27, -0.12], p = 0.038) and lower Aß42/Aß40 ratio (ß = -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 Aß of the APOE4 status. The mechanism underlying diet, metabolic response, and Aß peptide regulation must be elucidated.

Simple Carbohydrate Intake and Higher Risk for Physical Frailty Over 15 Years in Community-Dwelling Older Adults.

Insulin resistance is a major mechanism involved in the onset of physical frailty (PF). Although rich carbohydrate diets may promote insulin resistance, few studies have examined their association with PF risk. This study aimed to investigate the spectrum of carbohydrate exposure, including carbohydrate intake (simple, complex, and total), glycemic load (a measure of the diet-related insulin demand), and adherence to a low-carbohydrate diet with the incident risk of PF in community-dwelling older adults. Baseline carbohydrate exposure was assessed in nonfrail participants of the Three-City Bordeaux cohort using a 24-hour dietary recall. Over 15 years of follow-up, participants were screened for PF, defined by the FRAIL scale (≥3 criteria out of Fatigue, Resistance, Ambulation, Illnesses, and weight Loss). Associations were estimated using mixed-effects logistic models adjusted for sex, age, education, smoking status, alcohol consumption, depressive symptomatology, global cognitive performances, and protein and energy intakes. The sample included 1 210 participants (62% females, mean age 76 years). Over the follow-up, 295 (24%) incident cases of PF were documented (28% in females, 18% in males). Higher intake of simple carbohydrates was significantly associated with greater odds of incident PF (per 1-SD increased: OR = 1.29; 95% CI = 1.02-1.62), specifically among males (OR = 1.52; 95% CI = 1.04-2.22). No association was observed with complex or total carbohydrate intake, glycemic load, or low-carbohydrate diet. Among the whole carbohydrate exposure, only higher consumption of simple carbohydrates in older age was associated with a higher risk of developing PF. Further studies are required to explore underlying mechanisms.

Structural brain alterations in older adults exposed to early-life adversity.

BACKGROUND: Adverse childhood events may have differential effects on the brain that persist into adulthood. Findings on structural brain alterations in older adults exposed to early-life adversity are inconsistent notably due to heterogeneity in imaging studies, population, psychiatric comorbidities, nature of adverse events, and genetic vulnerability. This study examines whether exposure related to physical or sexual maltreatment, emotional maltreatment, and global adverse environment during childhood are associated with specific alterations in grey matter volumes and if this varies according to sex and serotonin transporter-linked promoter region (5-HTTLPR) genotype. METHOD: Structural MRI was used to acquire anatomical scans from 398 community-dwelling older adults. Quantitative regional estimates of 23 subregional volumes were derived using FreeSurfer software. Retrospective reporting of childhood adversity was collected using structured self-reported questionnaire. Analyses adjusted for age, sex, brain volume, head injury, lifetime depression and anxiety disorder, psychiatric medication, and cardiovascular ischemic pathologies. RESULTS: Exposure to adverse family environment was associated with smaller volumes of several frontal, cingulate, and parietal subregions and larger amygdala in the 5-HTTLPR SS genotype participants specifically but larger volumes of caudate, putamen, pallidum, and nucleus accumbens in the SL genotype participants. Highly significant differences were found with excessive sharing of parent problems with children, associated with larger grey-matter volumes in the thalamus and several frontal and parietal regions in 5-HTTLPR SL male participants specifically. CONCLUSIONS: Early-life adversity is associated with grey-matter volume alterations in older adults and this varies according to the type of adversity experienced, sex, and serotonergic genetic vulnerability; 5-HTTLPR SS participants appearing most vulnerable and SL individuals most resilient.

Late-life cynical hostility is associated with white matter alterations and the risk of Alzheimer's disease.

BACKGROUND: Cynical hostility (CH), a specific dimension of hostility that consists of a mistrust of others, has been suggested as a high-risk trait for dementia. However, the influence of CH on the incidence of Alzheimer's disease (AD) remains poorly understood. This study investigated whether late-life CH is associated with AD risk and structural neuroimaging markers of AD. METHODS: In community-dwelling older adults from the French ESPRIT cohort (n = 1388), incident dementia rate according to CH level was monitored during an 8-year follow-up and analyzed using Cox proportional hazards regression models. Brain magnetic resonance imaging volumes were measured at baseline (n = 508). Using automated segmentation procedures (Freesurfer 6.0), the authors assessed brain grey and white volumes on all magnetic resonance imaging scans. They also measured white matter hyperintensities volumes using semi-automated procedures. Mean volumes according to the level of CH were compared using ANOVA. RESULTS: Eighty-four participants developed dementia (32 with AD). After controlling for potential confounders, high CH was predictive of AD (HR 2.74; 95% CI 1.10-6.85; p = 0.030) and all dementia types are taken together (HR 2.30; 95% CI 1.10-4.80; p = 0.027). High CH was associated with white matter alterations, particularly smaller anterior corpus callosum volume (p < 0.01) after False Discovery Rate correction, but not with grey matter volumes. CONCLUSIONS: High CH in late life is associated with cerebral white matter alterations, designated as early markers of dementia, and higher AD risk. Identifying lifestyle and biological determinants related to CH could provide clues on AD physiopathology and avenues for prevention strategies.

High Glycemic Load Is Associated with Cognitive Decline in Apolipoprotein E ε4 Allele Carriers.

Recent evidence suggests that a high glycemic load (GL) diet is a risk factor for dementia, especially among apolipoprotein E ε4 allele (APOE4) carriers, while its association with cognitive decline is poorly known. Here, we investigated the association of high-GL meals with cognitive decline in older adults during a 12-year follow-up, according to their APOE4 carrier status. We used random-effect models and data from 2539 elderly participants from the Three-City study who completed a food frequency questionnaire (FFQ) to longitudinally assess the association of GL with changes in different cognitive domains (verbal fluency, visual memory, attention, visual motor processing speed, episodic memory). In APOE4 carriers, afternoon snack with high GL was significantly associated with cognitive decline in visual memory, episodic memory, and global cognition compared with APOE4 non-carriers. This study suggests a detrimental association between a high-GL diet and cognitive decline. The promotion of a low GL diet as a target to prevent cognitive decline in high-risk populations deserves more research.

Refined carbohydrate-rich diet is associated with long-term risk of dementia and Alzheimer's disease in apolipoprotein E ε4 allele carriers.

INTRODUCTION: In animal models, refined carbohydrates (RF) worsen Alzheimer's disease (AD). However, the long-term effects of high RF intake on the risk of dementia and AD are poorly described in epidemiological studies. Moreover, the interaction between RF and the apolipoprotein E ε4 allele (APOE-ε4) is unknown. Our study investigated whether RF-rich diets are associated with the risk of dementia and AD. METHODS: The glycemic load (GL) was quantified in 2777 elderly participants from the French Three-City Study to estimate RF intake. Then, the associations between GL and risk of dementia and AD, and the interaction with APOE-ε4 over a 12-year period were assessed using proportional hazards models. RESULTS: After adjustment for potential confounders, high afternoon-snack GL was associated with increased dementia and AD risk in APOE-ε4 carriers (hazard ratio = 1.27 [1.03-1.56]). DISCUSSION: This study highlights that RF-rich diets are a risk factor for dementia and AD in APOE-ε4 carriers.

Structural brain changes with lifetime trauma and re-experiencing symptoms is 5-HTTLPR genotype-dependent.

Background: Findings on structural brain alterations following trauma are inconsistent due probably to heterogeneity in imaging studies and population, clinical presentations, genetic vulnerability, and selection of controls. This study examines whether trauma and re-experiencing symptoms are associated with specific alterations in grey matter volumes and if this varies according to 5-HTTLPR genotype. Methods: Structural MRI was used to acquire anatomical scans from 377 community-dwelling older adults. Quantitative regional estimates of 22 subregional volumes were derived using FreeSurfer software. Lifetime trauma was assessed using the validated Watson's PTSD inventory, which evaluates the most severe trauma experienced according to DSM criteria. Analyses adjusted for age, sex, total brain volume, head injury, and comorbidities. Results: Of the 212 participants reporting lifetime trauma, 35.4% reported re-experiencing symptoms and for 1.9%, this was severe enough to meet criteria for full threshold PTSD. In participants with the SS 5-HTTLPR genotype only, re-experiencing symptoms were associated with smaller volumes in middle and superior temporal, frontal (lateral orbital, rostral and caudal middle) and parietal (precuneus, inferior and superior) regions. The trauma-exposed participants without re-experiencing symptoms were not significantly different from the non-trauma-exposed participants except for smaller precuneus and superior parietal region in traumatized participants and a larger amygdala in traumatized women specifically. Conclusions: In the non-clinical sample, lifetime trauma and re-experiencing symptoms were associated with smaller volume in prefrontal, temporal and parietal cortex subregions, and this varied according to serotonergic genetic vulnerability, 5-HTTLPR SS individuals being most susceptible.

Antecedentes: Los hallazgos sobre las alteraciones estructurales cerebrales luego del trauma son inconsistentes debido probablemente a heterogeneidad en los estudios de imagen y población, presentaciones clínicas, vulnerabilidad genética y selección de los controles. Este estudio examina si el trauma y los síntomas de reexperimentación están asociados con alteraciones específicas en los volúmenes de materia gris y si esto varía de acuerdo al genotipo 5-HTTLPR.Métodos: Se utilizó IMR estructural para adquirir mapeos anatómicos de 377 adultos mayores residentes en viviendas comunitarias. Se derivaron estimados regionales cuantitativos de 22 volúmenes sub-regionales usando el software FreeSurfer. Se evaluó trauma a través de la vida utilizando el inventario para TEPT validado de Watson, que evalúa el trauma más severo experimentado de acuerdo a criterios DSM. Se ajustaron los análisis por edad, sexo, volumen cerebral total, trauma encefálico y comorbilidades.Resultados: De los 212 participantes que reportaron trauma en la vida, un 35.4% reportó síntomas de reexperimentación y para el 1,9% fueron lo suficientemente severos para cumplir los criterios para el umbral completo del TEPT. Sólo en los participantes con el genotipo SS 5-HTTLPR, los síntomas de reexperimentación se asociaron con menores volúmenes en las regiones temporal media y superior, frontal (orbitolateral, rostral y caudal medial) y parietal (precúneo, inferior y superior). Los participantes expuestos a trauma sin síntomas de reexperimentación no variaron significativamente respecto a los no expuestos a trauma excepto por menor tamaño del precúneo y región superior parietal en los participantes traumatizados y un mayor tamaño de la amígdala específicamente en mujeres traumatizadas.Conclusiones: En una muestra no-clínica, el trauma a través de la vida y los síntomas de reexperimentación se asociaron con menor tamaño en sub-regiones corticales prefrontales, temporales y parietales, y esto varía de acuerdo a la vulnerabilidad genética serotoninérgica, siendo más susceptibles los individuos 5-HTTLPR SS.

Increased Serum C-reactive Protein and Corpus Callosum Alterations in Older Adults.

Chronic systemic low-grade inflammation is associated with aging, but little is known on whether age-related inflammation affects brain structure, particularly white matter. The current study tested the hypothesis that in older adults without dementia, higher serum levels of high-sensitivity C-reactive protein (hs-CRP) are associated with reduced corpus callosum (CC) areas. French community-dwelling subjects (ESPRIT study) aged 65 and older (N=101) underwent hs-CRP testing and structural magnetic resonance imaging (MRI). Multiple linear regression models were carried out. In the unadjusted model, higher hs-CRP level was significantly associated with smaller anterior, mid, and total midsagittal CC areas, but not with the posterior CC area. These associations were independent of demographic characteristics and intracranial volume. After adjustment for body mass index, diabetes, inflammation-related chronic pathologies and white matter lesions (WML), only the associations between hs-CRP level and smaller anterior and total midsagittal CC areas were still significant, although weaker. These findings suggest that low-grade inflammation is associated with CC structural integrity alterations in older adults independently of physical or neuropsychiatric pathologies.

Intake of Meat, Fish, Fruits, and Vegetables and Long-Term Risk of Dementia and Alzheimer's Disease.

BACKGROUND: The links between diet and the risk of dementia have never been studied considering the possibility of protopathic bias (i.e., reverse causation). OBJECTIVE: We aimed to examine the relationship between consumption frequency of meat, fish, fruits, and vegetables and long-term risk of dementia and Alzheimer's disease (AD), by taking into account this possibility. METHODS: We analyzed data of 5,934 volunteers aged 65 and over from the Three-city study who were followed every 2 to 4 years for 12 years. Dietary habits were assessed at inclusion using a brief food frequency questionnaire. The presence of symptoms of dementia was investigated at each follow-up visit. To limit the risk of protopathic bias, a 4-year lag window between exposure and disease assessment was implemented by excluding from the analyses all dementia cases that occurred during the first four years after inclusion. Analyses were performed using a Cox proportional hazard model and were adjusted for socio-demographic, lifestyle, and health factors. RESULTS: The average follow-up time was 9.8 years. During this period, 662 cases of dementia, including 466 of AD, were identified. After adjustment, only low meat consumption (≤1 time/week) was associated with an increased risk of dementia and AD compared with regular consumption (≥4 times/week) (HR = 1.58 95% CI = [1.17-2.14], HR = 1.67 95% CI = [1.18-2.37], respectively). No association was found between the consumption of fish, raw fruits, or cooked fruits and vegetables and the risk of dementia or AD. CONCLUSION: These findings suggest very low meat consumption increases the long-term risk of dementia and AD, and that a protopathic bias could have impacted finding from previous studies.

Depression Increases the Risk of Death Independently From Vascular Events in Elderly Individuals: The Three-City Study.

BACKGROUND: How much the association between depressive symptoms (DSs) and all-cause mortality depends on cardiovascular disease (CVD) events is poorly known. We aimed to prospectively quantify the association between DSs at repeated study visits and all-cause and cause-specific mortality, and the influence of incident CVD on this association. METHODS: The Three-City Study has included adults 65 years and older, who were examined at baseline between 1999 and 2001 and after 2, 4, 7, and 10 years of follow-up. At each visit, a score of 16 or greater on the 20-item Center for Epidemiologic Studies Depression Scale defined the presence of DSs. DS status and incident coronary heart disease or stroke events were used as time-dependent variables in a Cox proportional hazard model of mortality. RESULTS: We studied 7377 participants (63.7% females) aged 73.8 years (SD = 5.4 years) without a history of CVD at baseline examination. DSs were present in 19% to 22% of subjects at each study visit. During a median follow-up of 9.4 years, 650 subjects developed a first CVD, and 1255 had died. After adjustment for baseline sociodemographic variables, vascular risk factors, impairment in daily life activities, and antidepressants, time-dependent DSs were associated with a 28% increased risk of mortality (hazard ratio [HR] = 1.28; 95% confidence interval [CI] = 1.06-1.55), and incident CVD event was associated with a 63% increased risk (HR = 1.63; 95% CI = 1.30-2.04). However, the association between DSs and mortality was not influenced by the occurrence of CVD (HR for DS and CVD interaction = 1.03; 95% CI = 0.66-1.61). A mediation analysis confirmed that incident CVD only explained 6.9% of the excess of mortality associated with DSs. CONCLUSION: In older participants, the increased risk of all-cause mortality associated with the presence of DSs at baseline and during follow-up is not modified by and is moderately mediated by incident CVD. J Am Geriatr Soc 67:546-552, 2019.

Lifetime major depression and grey-matter volume

Background: There is evidence of structural brain alterations in major depressive disorder (MDD), but little is known about how these alterations might be affected by age at onset or genetic vulnerability. This study examines whether lifetime episodes of MDD are associated with specific alterations in grey-matter volume, and whether those alterations vary according to sex or serotonin transporter-linked promoter region (5-HTTLPR) genotype (LL, SL or SS). Methods: We used structural MRI to acquire anatomic scans from 610 community-dwelling participants. We derived quantitative regional estimates of grey-matter volume in 16 subregions using FreeSurfer software. We diagnosed MDD according to DSM-IV criteria. We adjusted analyses for age, sex, total brain volume, education level, head injury and comorbidities. Results: Lifetime MDD was associated with a smaller insula, thalamus, ventral diencephalon, pallidum and nucleus accumbens and with a larger pericalcarine region in both men and women. These associations remained after adjustment for false discovery rate. Lifetime MDD was also associated with a smaller caudate nucleus and amygdala in men and with a larger rostral anterior cingulate cortex in women. Late-onset first episodes of MDD (after age 50 years) were associated with a larger rostral anterior cingulate cortex and lingual and pericalcarine regions; early-onset MDD was associated with a smaller ventral diencephalon and nucleus accumbens. Some associations differed according to 5-HTTLPR genotype: the thalamus was smaller in participants with MDD and the LL genotype; pericalcarine and lingual volumes were higher in those with the SL genotype. Limitations: This study was limited by its cross-sectional design. Conclusion: Major depressive disorder was associated with persistent volume reductions in the deep nuclei and insula and with enlargements in visual cortex subregions; alterations varied according to age of onset and genotype.

Smaller hippocampal volume in current but not in past depression in comparison to healthy controls: Minor evidence from an older adults sample.

BACKGROUND: Structural neuroimaging studies revealed a consistent pattern of volumetric reductions in both hippocampus (HC) and anterior cingulate cortex (ACC) of individuals with major depressive episode(s) (MDE). This study investigated HC and ACC volume differences in currently depressed individuals (n = 150), individuals with a past lifetime MDE history (n = 79) and healthy controls (n = 287). METHODS: Non-demented individuals were recruited from a cohort of community-dwelling older adults (ESPRIT study). T1-weighted magnetic resonance images and FreeSurfer Software (automated method) were used. Concerning HC, a manual method of measurement dividing HC into head, body, and tail was also used. General Linear Model was applied adjusting for covariates. RESULTS: Current depression was associated with lower left posterior HC volume, using manual measurement, in comparison to healthy status. However, when we slightly changed sub-group inclusion criteria, results did not survive to correction for multiple comparisons. CONCLUSIONS: The finding of lower left posterior HC volume in currently depressed individuals but not in those with a past MDE compared to healthy controls could be related to brain neuroplasticity. Additionally, our results may suggest manual measures to be more sensitive than automated methods.

Psychological Pain in Suicidality: A Meta-Analysis.

OBJECTIVE: Perform a meta-analysis to quantify the association between psychological pain and current or lifetime history of suicidal ideation or suicide attempt. DATA SOURCES: Search MEDLINE, Web of Science, and PsycINFO from 1965 to 2015 for (psychache OR mental pain OR psychological pain) AND (suicid*). STUDY SELECTION: Observational case-control studies addressing the difference in psychological pain between individuals with and without current or lifetime history of suicidal ideation or suicide attempt. DATA EXTRACTION: Data were independently extracted into a standard electronic form. All authors were contacted for unpublished data related to current or lifetime history of suicide ideation or attempt. DATA SYNTHESIS: Twenty studies were included. Comparisons concerned 760 subjects with versus 8,803 subjects without lifetime history of suicide attempt; 344 subjects with versus 357 patients without current suicide attempt; 262 patients with versus 64 patients without lifetime history of suicidal ideation; and 551 subjects with versus 7,383 subjects without current suicidal ideation. The intensity of psychological pain was higher (1) in both subjects with lifetime history of suicide attempts and subjects with current suicide attempts versus without (effect sizes = 0.72, P < 10⁻² and 0.66, P < 10⁻², respectively) and (2) in both subjects with lifetime history of suicide ideation and subjects with current suicidal ideation versus without (effect sizes = 1.49, P = .01 and 1.15, P < 10⁻², respectively). Association between psychological pain and suicidality remained significant even when depression levels were not different between subjects. CONCLUSIONS: Higher psychological pain levels are associated with suicidal ideation and acts. Considering psychological pain to be at the core of suicidality is important for daily clinical practice and for the promotion of innovative therapeutic strategies for suicide prevention.

Repatriation is associated with isthmus cingulate cortex reduction in community-dwelling elderly.

OBJECTIVES: The impact of stressful life events (SLEs) on brain anatomy is poorly understood, particularly its long-term neural consequences. We tested the hypothesis that a serious SLE (repatriation of French citizens living in Algeria in 1962) is associated with changes in brain regions previously implicated in psychopathology (hippocampus, amygdala, corpus callosum, prefrontal cortex, anterior, posterior and isthmus cingulate cortex (ICC)) in a large elderly population. METHODS: Structural magnetic resonance imaging was used to acquire anatomical scans from 82 subjects repatriated from Algeria and 339 subjects without this experience or any other trauma. We derived quantitative regional estimates of subcortical volume using FreeSurfer Software. The General Linear Model was used to test the association between repatriation and changes in brain volume adjusted for confounders (gender, age, education, total brain volume, traumatic brain injury, Mini Mental State Examination score at baseline, current and lifetime major depression and recent SLEs). RESULTS: Repatriation to France was associated with reduced volume in a number of areas; however, only left and right ICC survived to false discovery rate correction. CONCLUSIONS: In the elderly a previous (approximately 40 years before) serious SLE could be associated with long-term volume reduction in the ICC, independently of psychopathology.