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.

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.

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.

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.

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.

Evaluation of a research diagnostic algorithm for DSM-5 neurocognitive disorders in a population-based cohort of older adults.

BACKGROUND: There is little information on the application and impact of revised criteria for diagnosing dementia and mild cognitive impairment (MCI), now termed major and mild neurocognitive disorders (NCDs) in the DSM-5. We evaluate a psychometric algorithm for diagnosing DSM-5 NCDs in a community-dwelling sample, and characterize the neuropsychological and functional profile of expert-diagnosed DSM-5 NCDs relative to DSM-IV dementia and International Working Group criteria for MCI. METHODS: A population-based sample of 1644 adults aged 72-78 years was assessed. Algorithmic diagnostic criteria used detailed neuropsychological data, medical history, longitudinal cognitive performance, and informant interview. Those meeting all criteria for at least one diagnosis had data reviewed by a neurologist (expert diagnosis) who achieved consensus with a psychiatrist for complex cases. RESULTS: The algorithm accurately classified DSM-5 major NCD (area under the curve (AUC) = 0.95, 95% confidence interval (CI) 0.92-0.97), DSM-IV dementia (AUC = 0.91, 95% CI 0.85-0.97), DSM-5 mild NCD (AUC = 0.75, 95% CI 0.70-0.80), and MCI (AUC = 0.76, 95% CI 0.72-0.81) when compared to expert diagnosis. Expert diagnosis of dementia using DSM-5 criteria overlapped with 90% of DSM-IV dementia cases, but resulted in a 127% increase in diagnosis relative to DSM-IV. Additional cases had less severe memory, language impairment, and instrumental activities of daily living (IADL) impairments compared to cases meeting DSM-IV criteria for dementia. DSM-5 mild NCD overlapped with 83% of MCI cases and resulted in a 19% increase in diagnosis. These additional cases had a subtly different neurocognitive profile to MCI cases, including poorer social cognition. CONCLUSION: DSM-5 NCD criteria can be operationalized in a psychometric algorithm in a population setting. Expert diagnosis using DSM-5 NCD criteria captured most cases with DSM-IV dementia and MCI in our sample, but included many additional cases suggesting that DSM-5 criteria are broader in their categorization.

GWAS-identified risk variants for major depressive disorder: Preliminary support for an association with late-life depressive symptoms and brain structural alterations.

A number of genome-wide association studies (GWAS) have investigated risk factors for major depressive disorder (MDD), however there has been little attempt to replicate these findings in population-based studies of depressive symptoms. Variants within three genes, BICC1, PCLO and GRM7 were selected for replication in our study based on the following criteria: they were identified in a prior MDD GWAS study; a subsequent study found evidence that they influenced depression risk; and there is a solid biological basis for a role in depression. We firstly investigated whether these variants were associated with depressive symptoms in our population-based cohort of 929 elderly (238 with clinical depressive symptoms and 691 controls), and secondly to investigate associations with structural brain alterations. A number of nominally significant associations were identified, but none reached Bonferroni-corrected significance levels. Common SNPs in BICC1 and PCLO were associated with a 50% and 30% decreased risk of depression, respectively. PCLO rs2522833 was also associated with the volume of grey matter (p=1.6×10(-3)), and to a lesser extent with hippocampal volume and white matter lesions. Among depressed individuals rs9870680 (GRM7) was associated with the volume of grey and white matter (p=10(-4) and 8.3×10(-3), respectively). Our results provide some support for the involvement of BICC1 and PCLO in late-life depressive disorders and preliminary evidence that these genetic variants may also influence brain structural volumes. However effect sizes remain modest and associations did not reach corrected significance levels. Further large imaging studies are needed to confirm our findings.

Corpus callosum size may predict late-life depression in women: a 10-year follow-up study.

BACKGROUND: Recent research on late-life depression (LLD) pathophysiology suggests the implication of abnormalities in cerebral white matter and particularly in interhemispheric transfer. Corpus callosum (CC) is the main brain interhemispheric commissure. Hence, we investigated the association between baseline CC measures and risk of LDD. METHODS: We studied 467 non-demented individuals without LLD at baseline from a cohort of elderly community-dwelling people (the ESPRIT study). LLD was assessed at year 2, 4, 7 and 10 of the study follow-up. At baseline, T1-weighted magnetic resonance images were manually traced to measure the mid-sagittal areas of the anterior, mid and posterior CC. Multivariate Cox proportional hazards models stratified by sex were used to predict LLD incidence over 10 years. RESULTS: A significant interaction between gender and CC size was found (p=0.02). LLD incidence in elderly women, but not in men, was significantly associated with smaller anterior (HR 1.37 [1.05-1.79] p=0.017), mid (HR 1.43 [1.09-1.86] p=0.008), posterior (HR 1.39 [1.12-1.74] p=0.002) and total (HR 1.53 [1.16-2.00] p=0.002) CC areas at baseline in Cox models adjusted for age, education, global cognitive impairment, ischemic pathologies, left-handedness, white matter lesion, intracranial volume and past depression. LIMITATIONS: The main limitation was the retrospective assessment of major depression. CONCLUSION: Smaller CC size is a predictive factor of incident LLD over 10 years in elderly women independently of cognitive deterioration. Our finding suggests a possible role of CC and reduced interhemispheric connectivity in LLD pathophysiology. Extensive explorations are needed to clarify the mechanisms leading to CC morphometric changes in mood disorders.

Brain volumes in late life: gender, hormone treatment, and estrogen receptor variants.

Structural imaging studies suggest gender differences in brain volumes; however, whether hormone treatment (HT) can protect against age-related structural changes remains unknown, and no prior neuroimaging study has investigated potential interactions between HT and estrogen receptor (ESR) polymorphisms. Magnetic resonance imaging was used to measure gray and white matter, hippocampal volume, corpus callosum, cerebrospinal fluid (CSF), total intracranial volume (ICV) and white matter lesions (WML) in 582 non-demented older adults. In multivariable analysis, when compared to women who had never used HT, men and women currently on treatment, but not past users, had significantly smaller ratios of gray matter to ICV and increased atrophy (CSF/ICV ratio). Hippocampal and white matter volume as well as the corpus callosum area were not significantly different across groups. ESR2 variants were not significantly associated with brain measures, but women with the ESR1 rs2234693 C allele had significantly smaller WML. Furthermore this association was modified by HT use. Our results do not support a beneficial effect of HT on brain volumes in older women, but suggest the potential involvement of ESR1 in WML.

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.

Hippocampal sulcal cavities in depression and healthy individuals.

BACKGROUND: A literature review suggested age and cognitive problems to be related to an increased prevalence of small areas of signal variation within the hippocampus observed on MRI, described as hippocampal sulcal cavities (HSCs; (Maller et al., 2011)). The current study aimed to describe the prevalence of HSCs in patients with treatment-resistant depression (TRD) and healthy controls over a large age-range. METHODS: 115 TRD patients and 86 controls underwent MRI brain scanning. Right and left HSCs were rated separately for prevalence and length. RESULTS: HSCs were observed in 73.04% of those with TRD, statistically more prevalent (p=0.001) than amongst controls (51.16%). These findings are consistent with our review (66% prevalence in memory disorders and 47% in healthy controls). Furthermore, HSC presence and length was associated with aging. LIMITATIONS: The study was cross-sectional so its implications for aging are tentative. A larger sample scanned longitudinally will allow for more sophisticated statistical methods by which to investigate the relationship between HSCs, aging, and TRD. CONCLUSIONS: Although their clinical significance remains uncertain, the results of the current study suggest that HSCs are related with age and those with TRD have more aged brains than their peers.

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.

La conducta suicida se asocia a una reducción el área del cuerpo calloso / Suicidal behavior is associated with reduced corpus callosum area

Antecedentes. El tamaño del cuerpo calloso (CC) se ha relacionado con la presencia de déficits cognitivos y emocionales en diversos trastornos neuropsiquiátricos y del estado de ánimo. Dado que estos déficits se observan también en la conducta suicida, hemos investigado específicamente la asociación entre la atrofia del CC y dicha conducta. Métodos. Estudiamos a 435 individuos diestros, sin demencia, de una cohorte de base comunitaria formada por personas de edad igual o superior a 65 años (estudio ESPRIT). Dividimos a los participantes en 3 grupos: individuos con intentos de suicidio (n=21), individuos de control afectivos (CA) (n=180) sin antecedentes de intentos de suicidio pero con antecedentes de depresión, e individuos de control sanos (CS) (n=234). Se utilizaron imágenes de resonancia magnética con ponderación T1 para medir las áreas mesosagitales del CC anterior, medio y posterior. Se aplicó un análisis de covarianza multivariado para comparar las áreas del CC de los 3 grupos. Resultados. Los análisis multivariados, con un ajuste en cuanto a edad, sexo, trauma infantil, traumatismo craneal y volumen encefálico total, mostraron que el área del tercio posterior del CC era significativamente menor en los individuos con intentos de suicidio, en comparación con los CA (p=0,020) y los CS (p=0,010). No se observaron diferencias significativas entre CA y CS. No hubo diferencias en cuanto a los tercios anterior y medio del CC. Conclusiones. Nuestros resultados resaltan la presencia de un tamaño reducido del tercio posterior del CC en los individuos con antecedentes de suicidio, lo cual sugiere una disminución de la conectividad interhemisférica y un posible papel del CC en la fisiopatología de la conducta suicida. Serán necesarios nuevos estudios para confirmar estos resultados y esclarecer las alteraciones celulares subyacentes que conducen a estas diferencias morfométricas (AU)

Background. Corpus callosum (CC) size has been associated with cognitive and emotional deficits in a range of neuropsychiatric andmood disorders. As such deficits are also found in suicidal behavior, we investigated specifically the association between CC atrophy and suicidal behavior. Methods. We studied 435 right-handed individuals without dementia from a cohort of community-dwelling persons aged 65 years and over (the ESPRIT study). They were divided in three groups: suicide attempters (n=21), affective control subjects (AC) (n=180) without history of suicide attempt but with a history of depression, and healthy control subjects (HC) (n=234). T1-weighted magnetic resonance images were traced to measure the midsagittal areas of the anterior, mid, and posterior CC. Multivariate analysis of covariance was used to compare CC areas in the 3 groups. Results. Multivariate analyses adjusted for age, gender, childhood trauma, head trauma, and total brain volume showed that the area of the posterior third of CC was significantly smaller in suicide attempters than in AC (P=.020) and HC (P=.010) individuals. No significant differences were found between AC and HC. No differences were found for the anterior and mid thirds of the CC. Conclusions. Our findings emphasize a reduced size of the posterior third of the CC in subjects with a history of suicide, suggesting a diminished interhemispheric connectivity and a possible role of CC in the pathophysiology of suicidal behavior. Further studies are needed to strengthen these results and clarify the underlying cellular changes leading to these morphometric differences (AU)

Depression in elderly persons subject to childhood maltreatment is not modulated by corpus callosum and hippocampal loss.

Childhood adversity has been observed to engender structural changes in the hippocampus and corpus callosum associated with increased risk for depression in childhood and early adulthood. This study investigated this association in the elderly. Corpus callosum area and hippocampal volume were measured from structural MRI in 427 community dwelling elderly. Information on childhood adversity was obtained in the course of a clinical examination using a questionnaire covering multiple aspects of abuse. Multivariate analyses found a significant increase in corpus callosum area and hippocampal volume in subjects exposed to mental disorder in parents and poverty, respectively. No association was found with childhood sexual and physical abuse.