Dairy products and brain structure in French older adults.

Among food groups with putative benefits for brain structures, dairy products (DP) have been poorly studied. The sample included participants without dementia from the ancillary brain imaging study of the Three-City cohort who were aged 65+ years, had their DP intake assessed with a FFQ at baseline and underwent an anatomical scan 3 years (n 343) or 9 years (n 195) after completing the dietary survey. The frequencies of consumption of total DP, milk and cheese were not associated with brain structure. Compared with the lowest frequency, the highest frequency of fresh DP (F-DP) consumption (< 0·5 v. > 1·5 times/d) was significantly associated with a lower medial temporal lobe volume (MTLV) (ß = -1·09 cm3, 95 % CI - 1·83, -0·36) 9 years later. In this population-based study of older adults, the consumption of F-DP more than 1·5 times/d was associated with a lower MTLV, which is considered an early biomarker of Alzheimer's disease, 9 years later. This original study should be replicated in different settings before conclusions are drawn.

Understanding the relationship between type-2 diabetes, MRI markers of neurodegeneration and small vessel disease, and dementia risk: a mediation analysis.

To explore to which extent neurodegeneration and cerebral small vessel disease (SVD) could mediate the association between type-2 diabetes and higher dementia risk. The analytical sample consisted in 2228 participants, out of the Three-City study, aged 65 and older, free of dementia at baseline who underwent brain MRI. Diabetes was defined by medication intake or fasting or non-fasting elevated glucose levels. Dementia status was assessed every 2 to 3 years, during up to 12 years of follow-up. Brain parenchymal fraction (BPF) and white matter hyperintensities volume (WMHV) were selected as markers of neurodegeneration and cerebral SVD respectively. We performed a mediation analysis of the effect of baseline BPF and WMHV (mediators) on the association between diabetes and dementia risk using linear and Cox models adjusted for age, sex, education level, hypertension, hypercholesterolemia, BMI, smoking and alcohol drinking status, APOE-ε4 status, and study site. At baseline, 8.8% of the participants had diabetes. Diabetes (yes vs. no) was associated with higher WMHV (ßdiab = 0.193, 95% CI 0.040; 0.346) and lower BPF (ßdiab = -0.342, 95% CI -0.474; -0.210), as well as with an increased risk of dementia over 12 years of follow-up (HRdiab = 1.65, 95% CI 1.04; 2.60). The association between diabetes status and dementia risk was statistically mediated by higher WMHV (HRdiab=1.05, 95% CI 1.01; 1.11, mediated part = 10.8%) and lower BPF (HRdiab = 1.12, 95% CI 1.05; 1.20, mediated part = 22.9%). This study showed that both neurodegeneration and cerebral SVD statistically explained almost 30% of the association between diabetes and dementia.

Anatomical MRI staging of frontotemporal dementia variants.

INTRODUCTION: The three clinical variants of frontotemporal dementia (behavioral variant [bvFTD], semantic dementia, and progressive non-fluent aphasia [PNFA]) are likely to develop over decades, from the preclinical stage to death. METHODS: To describe the long-term chronological anatomical progression of FTD variants, we built lifespan brain charts of normal aging and FTD variants by combining 8022 quality-controlled MRIs from multiple large-scale data-bases, including 107 bvFTD, 44 semantic dementia, and 38 PNFA. RESULTS: We report in this manuscript the anatomical MRI staging schemes of the three FTD variants by describing the sequential divergence of volumetric trajectories between normal aging and FTD variants. Subcortical atrophy precedes focal cortical atrophy in specific behavioral and/or language networks, with a "radiological" prodromal phase lasting 8-10 years (time elapsed between the first structural alteration and canonical cortical atrophy). DISCUSSION: Amygdalar and striatal atrophy can be candidate biomarkers for future preclinical/prodromal FTD variants definitions. HIGHLIGHTS: We describe the chronological MRI staging of the most affected structures in the three frontotemporal dementia (FTD) syndromic variants. In behavioral variant of FTD (bvFTD): bilateral amygdalar, striatal, and insular atrophy precedes fronto-temporal atrophy. In semantic dementia: bilateral amygdalar atrophy precedes left temporal and hippocampal atrophy. In progressive non-fluent aphasia (PNFA): left striatal, insular, and thalamic atrophy precedes opercular atrophy.

Hippocampal-amygdalo-ventricular atrophy score: Alzheimer disease detection using normative and pathological lifespan models.

In this article, we present an innovative MRI-based method for Alzheimer disease (AD) detection and mild cognitive impairment (MCI) prognostic, using lifespan trajectories of brain structures. After a full screening of the most discriminant structures between AD and normal aging based on MRI volumetric analysis of 3,032 subjects, we propose a novel Hippocampal-Amygdalo-Ventricular Atrophy score (HAVAs) based on normative lifespan models and AD lifespan models. During a validation on three external datasets on 1,039 subjects, our approach showed very accurate detection (AUC ≥ 94%) of patients with AD compared to control subjects and accurate discrimination (AUC = 78%) between progressive MCI and stable MCI (during a 3-year follow-up). Compared to normative modeling, classical machine learning methods and recent state-of-the-art deep learning methods, our method demonstrated better classification performance. Moreover, HAVAs simplicity makes it fully understandable and thus well-suited for clinical practice or future pharmaceutical trials.

Striatal and cerebellar vesicular acetylcholine transporter expression is disrupted in human DYT1 dystonia.

Early-onset torsion dystonia (TOR1A/DYT1) is a devastating hereditary motor disorder whose pathophysiology remains unclear. Studies in transgenic mice suggested abnormal cholinergic transmission in the putamen, but this has not yet been demonstrated in humans. The role of the cerebellum in the pathophysiology of the disease has also been highlighted but the involvement of the intrinsic cerebellar cholinergic system is unknown. In this study, cholinergic neurons were imaged using PET with 18F-fluoroethoxybenzovesamicol, a radioligand of the vesicular acetylcholine transporter (VAChT). Here, we found an age-related decrease in VAChT expression in the posterior putamen and caudate nucleus of DYT1 patients versus matched controls, with low expression in young but not in older patients. In the cerebellar vermis, VAChT expression was also significantly decreased in patients versus controls, but independently of age. Functional connectivity within the motor network studied in MRI and the interregional correlation of VAChT expression studied in PET were also altered in patients. These results show that the cholinergic system is disrupted in the brain of DYT1 patients and is modulated over time through plasticity or compensatory mechanisms.

Distinct Hippocampal Subfields Atrophy in Older People With Vascular Brain Injuries.

BACKGROUND AND PURPOSE: Many neurological or psychiatric diseases affect the hippocampus during aging. The study of hippocampal regional vulnerability may provide important insights into the pathophysiological mechanisms underlying these processes; however, little is known about the specific impact of vascular brain damage on hippocampal subfields atrophy. METHODS: To analyze the effect of vascular injuries independently of other pathological conditions, we studied a population-based cohort of nondemented older adults, after the exclusion of people who were diagnosed with neurodegenerative diseases during the 14-year clinical follow-up period. Using an automated segmentation pipeline, 1.5T-magnetic resonance imaging at inclusion and 4 years later were assessed to measure both white matter hyperintensities and hippocampal subfields volume. Annualized rates of white matter hyperintensity progression and annualized rates of hippocampal subfields atrophy were then estimated in each participant. RESULTS: We included 249 participants in our analyses (58% women, mean age 71.8, median Mini-Mental State Evaluation 29). The volume of the subiculum at baseline was the only hippocampal subfield volume associated with total, deep/subcortical, and periventricular white matter hyperintensity volumes, independently of demographic variables and vascular risk factors (ß=-0.17, P=0.011; ß=-0.25, P=0.020 and ß=-0.14, P=0.029, respectively). In longitudinal measures, the annualized rate of subiculum atrophy was significantly higher in people with the highest rate of deep/subcortical white matter hyperintensity progression, independently of confounding factors (ß=-0.32, P=0.014). CONCLUSIONS: These cross-sectional and longitudinal findings highlight the links between vascular brain injuries and a differential vulnerability of the subiculum within the hippocampal loop, unbiased of the effect of neurodegenerative diseases, and particularly when vascular injuries affect deep/subcortical structures.

Toward a unified analysis of cerebellum maturation and aging across the entire lifespan: A MRI analysis.

Previous literature about the structural characterization of the human cerebellum is related to the context of a specific pathology or focused in a restricted age range. In fact, studies about the cerebellum maturation across the lifespan are scarce and most of them considered the cerebellum as a whole without investigating each lobule. This lack of study can be explained by the lack of both accurate segmentation methods and data availability. Fortunately, during the last years, several cerebellum segmentation methods have been developed and many databases comprising subjects of different ages have been made publically available. This fact opens an opportunity window to obtain a more extensive analysis of the cerebellum maturation and aging. In this study, we have used a recent state-of-the-art cerebellum segmentation method called CERES and a large data set (N = 2,831 images) from healthy controls covering the entire lifespan to provide a model for 12 cerebellum structures (i.e., lobules I-II, III, IV, VI, Crus I, Crus II, VIIB, VIIIA, VIIIB, IX, and X). We found that lobules have generally an evolution that follows a trajectory composed by a fast growth and a slow degeneration having sometimes a plateau for absolute volumes, and a decreasing tendency (faster in early ages) for normalized volumes. Special consideration is dedicated to Crus II, where slow degeneration appears to stabilize in elder ages for absolute volumes, and to lobule X, which does not present any fast growth during childhood in absolute volumes and shows a slow growth for normalized volumes.

Severity of Small Vessel Disease Biomarkers Reduces the Magnitude of Cognitive Recovery after Ischemic Stroke.

OBJECTIVE: The objective of this study was to evaluate the impact of radiological biomarkers suggestive of cerebral small vessel disease (SVD) on the evolution of cognitive performances after an ischemic stroke (IS). METHODS: We studied patients with a supratentorial IS recruited consecutively to a prospective monocentric longitudinal study. A cognitive assessment was performed at baseline, 3 months, and 1 year and was based on a Montreal Cognitive Assessment, an Isaacs set test of verbal fluency (IST), and a Zazzo's cancellation task (ZCT) for the evaluation of attentional functions and processing speed. The following cerebral SVD biomarkers were detected on a 3-T brain MRI performed at baseline: white matter hyperintensities (WMHs), deep and lobar microbleeds, enlarged perivascular spaces in basal ganglia and centrum semiovale, previous small deep infarcts, and cortical superficial siderosis (cSS). Generalized linear mixed models were used to evaluate the relationship between these biomarkers and changes in cognitive performances. RESULTS: A total of 199 patients (65 ± 13 years, 68% male) were analyzed. Overall, the cognitive performances improved, more significantly in the first 3 months. Severe WMH was identified in 34% of the patients, and focal cSS in 3.5%. Patients with severe WMH and focal cSS had overall worse cognitive performances. Those with severe WMH had less improvement over time for IST (ß = -0.16, p = 0.02) and the number of errors to ZCT (ß = 0.19, p = 0.02), while those with focal cSS had less improvement over time for ZCT completion time (ß = 0.14, p = 0.01) and number of errors (ß = 0.17, p = 0.008), regardless of IS volume and location, gray matter volume, demographic confounders, and clinical and cardiovascular risk factors. CONCLUSION: The severity of SVD biomarkers, encompassing WMH and cSS, seems to reduce the magnitude of cognitive recovery after an IS. The detection of such SVD biomarkers early after stroke might help to identify patients with a cognitive vulnerability and a higher risk of poststroke cognitive impairment.

Normal-Appearing White Matter Integrity Is a Predictor of Outcome After Ischemic Stroke.

Background and Purpose- The aim of the present study was to evaluate the relationship between normal-appearing white matter (NAWM) integrity and postischemic stroke recovery in 4 main domains including cognition, mood, gait, and dependency. Methods- A prospective study was conducted, including patients diagnosed for an ischemic supratentorial stroke on a 3T brain MRI performed 24 to 72 hours after symptom onset. Clinical assessment 1 year after stroke included a Montreal Cognitive Assessment, an Isaacs set test, a Zazzo cancelation task, a Hospital Anxiety and Depression scale, a 10-meter walking test, and a modified Rankin Scale (mRS). Diffusion tensor imaging parameters in the NAWM were computed using FMRIB (Functional Magnetic Resonance Imaging of the Brain) Diffusion Toolbox. The relationships between mean NAWM diffusion tensor imaging parameters and the clinical scores were assessed using linear and ordinal regression analyses, including the volumes of white matter hyperintensities, gray matter, and ischemic stroke as radiological covariates. Results- Two hundred seven subjects were included (66±13 years old; 67% men; median National Institutes of Health Stroke Scale score, 3; interquartile range, 2-6). In the models including only radiological variables, NAWM fractional anisotropy was associated with the mRS and the cognitive scores. After adjusting for demographic confounders, NAWM fractional anisotropy remained a significant predictor of mRS (ß=-0.24; P=0.04). Additional path analysis showed that NAWM fractional anisotropy had a direct effect on mRS (ß=-0.241; P=0.001) and a less important indirect effect mediating white matter hyperintensity burden. Similar results were found with mean diffusivity, axial diffusivity, and radial diffusivity. In further subgroup analyses, a relationship between NAWM integrity in widespread white matter tracts, mRS, and Isaacs set test was found in right hemispheric strokes. Conclusions- NAWM diffusion tensor imaging parameters measured early after an ischemic stroke are independent predictors of functional outcome and may be additional markers to include in studies evaluating poststroke recovery.

Learning-driven cerebellar intrinsic functional connectivity changes in men.

Learning involves distributed but coordinated activity among the widespread connected brain areas. Increase in areas connections' strength may be established offline, that is, aside from the task itself, in a resting-state. The resulting functional connectivity may hence constitute a neural trace of the learning episode. The present study examined whether a conditional visuomotor learning task previously shown to activate the cerebellum would modify cerebellar intrinsic connectivity in groups of young and older male subjects. In the group of young subjects, resting-state connectivity within several cerebellar networks (fronto-cerebellar, temporo-cerebellar, cerebello-cerebellar) was modified following the task. In most cases, modulation resulted in increased anticorrelations between cerebellar and cortical areas and the amplitude of changes was correlated with learning efficacy. The group of older subjects drastically differed, with sparser modifications of resting-state functional connectivity and no cerebellar networks involved. The findings of this exploratory study indicate that associative learning modifies the strength of intrinsic connectivity in young subjects but to a lesser degree in older subjects. They further suggest that functional connectivity within cerebellar networks may play an operative role in this kind of learning.

Blood polyunsaturated omega-3 fatty acids, brain atrophy, cognitive decline, and dementia risk.

INTRODUCTION: We searched for consistent associations of an omega-3 index in plasma (sum of eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) with several dementia-related outcomes in a large cohort of older adults. METHODS: We included 1279 participants from the Three-City study, non-demented at the time of blood measurements at baseline, with face-to-face neuropsychological assessment and systematic detection of incident dementia over a 17-year follow-up. An ancillary study included 467 participants with up to three repeated brain imaging exams over 10 years. RESULTS: In multivariable models, higher levels of plasma EPA+DHA were consistently associated with a lower risk of dementia (hazard ratio for 1 standard deviation = 0.87 [95% confidence interval, 0.76-0.98]), and a lower decline in global cognition (P = .04 for change over time), memory (P = .06), and medial temporal lobe volume (P = .02). DISCUSSION: This prospective study provides compelling evidence for a relationship between long-chain omega-3 fatty acids levels and lower risks for dementia and related outcomes.

Chronic Cortical Cerebral Microinfarcts Slow Down Cognitive Recovery After Acute Ischemic Stroke.

Background and Purpose- Cortical cerebral microinfarcts (CMIs) have been associated with vascular dementia and Alzheimer disease. The aim of the present study was to evaluate the role of cortical CMI detected on 3T magnetic resonance imaging, on the evolution of cognition during the year following an acute ischemic stroke. Methods- We conducted a prospective and monocentric study, including patients diagnosed for a supratentorial ischemic stroke with a National Institutes of Health Stroke Scale score ≥1, without prestroke dementia or neurological disability. Cortical CMIs were assessed on a brain 3T magnetic resonance imaging realized at baseline, as well as markers of small vessel disease, stroke characteristics, and hippocampal atrophy. Cognitive assessment was performed at 3 time points (baseline, 3 months, and 1 year) using the Montreal Cognitive Assessment, the Isaacs set test, and the Zazzo's cancellation task. Generalized linear mixed models were performed to evaluate the relationships between the number of cortical CMI and changes in cognitive scores over 1 year. Results- Among 199 patients (65±13 years old, 68% men), 88 (44%) had at least one cortical CMI. Hypertension was the main predictor of a higher cortical CMI load (B=0.58, P=0.005). The number of cortical CMI was associated with an increase time at the Zazzo's cancellation task over 1 year (B=3.84, P=0.01), regardless of the other magnetic resonance imaging markers, stroke severity, and demographic factors. Conclusions- Cortical CMIs are additional magnetic resonance imaging markers of poorer processing speed after ischemic stroke. These results indicate that a high load of cortical CMI in patients with stroke can be considered as a cerebral frailty condition which counteracts to the recovery process, suggesting a reduced brain plasticity among these patients.

Gliovascular changes precede white matter damage and long-term disorders in juvenile mild closed head injury.

Traumatic brain injury (TBI) is a leading cause of hospital visits in pediatric patients and often leads to long-term disorders even in cases of mild severity. White matter (WM) alterations are commonly observed in patients months or years after the injury assessed by magnetic resonance imaging (MRI), but little is known about WM pathophysiology early after mild pediatric TBI. To evaluate the status of the gliovascular unit in this context, mild TBI was induced in postnatal-day 17 mice using a closed head injury model with two grades of severity (G1, G2). G2 resulted in significant WM edema (increased T2-signal) and BBB damage (IgG-extravasation immunostaining) whereas decreased T2 and the increased levels of astrocytic water-channel AQP4 were observed in G1 mice 1 day post-injury. Both severities induced astrogliosis (GFAP immunolabeling). No changes in myelin and neurofilament were detected at this acute time point. One month after injury G2 mice exhibited diffusion tensor imaging MRI alterations (decreased fractional anisotropy) accompanied by decreased neurofilament staining in the WM. Both severities induced behavioral impairments at this time point. In conclusion, long-term deficits and WM changes similar to those found after clinical TBI are preceded by distinct early gliovascular phenotype alterations after juvenile mild TBI, revealing AQP4 as a potential candidate for severity-based treatments.

Admission Brain Cortical Volume: An Independent Determinant of Poststroke Cognitive Vulnerability.

BACKGROUND AND PURPOSE: Several markers of poststroke cognitive impairment have been reported. The role of brain cortical volume remains uncertain. The aim of this study was to evaluate the influence of brain cortical volume on cognitive outcomes using a voxel-based morphometry approach in subjects without prestroke dementia. METHODS: Ischemic stroke patients were prospectively recruited 24 to 72 hours post stroke (M0). Cognition was evaluated at M0, 3 months, and 1 year (M12) using the Montreal Cognitive Assessment, the Isaacs set test, and the Zazzo's cancellation task. A 3-T brain magnetic resonance imaging was performed at M0. Grey matter (GM) was segmented using Statistical Parametric Mapping 12 software. Association between global GM volume and cognitive score slopes between M0 and M12 was evaluated using a linear mixed model. Correlations between focal GM volumes and changes in cognitive performance were evaluated using Statistical Parametric Mapping 12. RESULTS: Two-hundred forty-eight patients were included (mean age 65±SD 14 years old, 66% men). Global GM volume was significantly associated with changes in Montreal Cognitive Assessment scores (ß=0.01; P=0.04) and in the number of errors on the Zazzo's cancellation task (ß=-0.02; P=0.04) independently of other clinical/radiological confounders. Subjects with lower GM volumes in the left fronto-temporo-insular cortex were more vulnerable to transient Montreal Cognitive Assessment and Isaacs set test impairment. Subjects with lower GM volumes in right temporo-insular cortex, together with basal ganglia, were more vulnerable to transient cognitive impairment on the Zazzo's cancellation task. CONCLUSIONS: Smaller cortical volumes in fronto-temporo-insular areas measured 24 to 72 hours post stroke are associated with cognitive vulnerability in the subacute stroke phase.

Activity/rest cycle and disturbances of structural backbone of cerebral networks in aging.

OBJECTIVE: Although aging is associated with alterations of both activity/rest cycle and brain structure, few studies have evaluated associations between these processes. The aim of this study was to examine relationship between activity/rest cycle quality and brain structural integrity in aging subjects by exploring both grey and white matter compartments. MATERIAL AND METHODS: Fifty-eight elderly subjects (76±0.5 years; 41% female) without dementia, sleep disorders and medications were included in the analysis. Actigraphy was used to measure parameters of activity/rest cycle (24-h amplitude, 24-h fragmentation and 24-h stability) and sleep (total sleep time and sleep fragmentation) over a minimal period of 5 days. Whole brain linear regression analyses were performed on grey matter volumes maps using voxel based morphometry and on white matter integrity using tract based statistics analyses. RESULTS: A lower 24-h amplitude and a higher sleep fragmentation were independently associated with a reduction of white matter integrity in models including age and gender as covariates. The association between 24-h amplitude and white matter integrity decreased but remained significant in a model accounted for sleep fragmentation, indicating a specific effect of 24-h cycle disturbances. No association with grey matter volumes was observed. CONCLUSION: In elderly, not only sleep but also 24-h cycle disturbances were associated with altered structural connectivity. This alteration of structural backbone networks related to activity/rest cycle disturbances in aging might constitute a cerebral frailty factor for the development of cognitive impairment.

Towards a unified analysis of brain maturation and aging across the entire lifespan: A MRI analysis.

There is no consensus in literature about lifespan brain maturation and senescence, mainly because previous lifespan studies have been performed on restricted age periods and/or with a limited number of scans, making results instable and their comparison very difficult. Moreover, the use of nonharmonized tools and different volumetric measurements lead to a great discrepancy in reported results. Thanks to the new paradigm of BigData sharing in neuroimaging and the last advances in image processing enabling to process baby as well as elderly scans with the same tool, new insights on brain maturation and aging can be obtained. This study presents brain volume trajectory over the entire lifespan using the largest age range to date (from few months of life to elderly) and one of the largest number of subjects (N = 2,944). First, we found that white matter trajectory based on absolute and normalized volumes follows an inverted U-shape with a maturation peak around middle life. Second, we found that from 1 to 8-10 y there is an absolute gray matter (GM) increase related to body growth followed by a GM decrease. However, when normalized volumes were considered, GM continuously decreases all along the life. Finally, we found that this observation holds for almost all the considered subcortical structures except for amygdala which is rather stable and hippocampus which exhibits an inverted U-shape with a longer maturation period. By revealing the entire brain trajectory picture, a consensus can be drawn since most of the previously discussed discrepancies can be explained. Hum Brain Mapp 38:5501-5518, 2017. © 2017 Wiley Periodicals, Inc.

Semantic retrieval over time in the aging brain: Structural evidence of hippocampal contribution.

This study investigates relationship between regional cerebral volumes and performances over time of a categorical fluency task, in a sample of older adults (n = 316). Using voxel-wise technique, the relationship between local grey matter volume and Isaacs Set Test (IST) scores at its early (first 15 sec) and late (last 15 sec) phase production was analyzed with a linear regression model adjusting for age, sex, educational level, ApoEɛ4 allele, handedness and Grey Matter atrophy. Lower early IST scores were associated with smaller volumes in bilateral inferior frontal gyri and in right thalamus, whereas lower late IST scores were associated to smaller left inferior parietal gyrus and left anterior hippocampus. An analysis based on automatic segmentation of hippocampus confirmed the latest relationship which cannot be attributed to the correlation of each variable with global cognitive impairment because it remained when MMSE was accounted for. We observed a switch from frontal to temporo-parietal regions as words retrieval become more difficult over time. Automatic speech production of the early phase of the category fluency task is dependent on executive networks integrity whereas controlled speech production of the late phase is dependent on memory networks integrity, including left hippocampus. These results are concordant with recent imaging studies expanding the implication of hippocampus to semantic memory performances and they underlie the need to consider verbal fluency task over time.

Detection of Alzheimer's disease signature in MR images seven years before conversion to dementia: Toward an early individual prognosis.

Finding very early biomarkers of Alzheimer's Disease (AD) to aid in individual prognosis is of major interest to accelerate the development of new therapies. Among the potential biomarkers, neurodegeneration measurements from MRI are considered as good candidates but have so far not been effective at the early stages of the pathology. Our objective is to investigate the efficiency of a new MR-based hippocampal grading score to detect incident dementia in cognitively intact patients. This new score is based on a pattern recognition strategy, providing a grading measure that reflects the similarity of the anatomical patterns of the subject under study with dataset composed of healthy subjects and patients with AD. Hippocampal grading was evaluated on subjects from the Three-City cohort, with a followup period of 12 years. Experiments demonstrate that hippocampal grading yields prediction accuracy up to 72.5% (P < 0.0001) 7 years before conversion to AD, better than both hippocampal volume (58.1%, P = 0.04) and MMSE score (56.9%, P = 0.08). The area under the ROC curve (AUC) supports the efficiency of imaging biomarkers with a gain of 8.4 percentage points for hippocampal grade (73.0%) over hippocampal volume (64.6%). Adaptation of the proposed framework to clinical score estimation is also presented. Compared with previous studies investigating new biomarkers for AD prediction over much shorter periods, the very long followup of the Three-City cohort demonstrates the important clinical potential of the proposed imaging biomarker. The high accuracy obtained with this new imaging biomarker paves the way for computer-based prognostic aides to help the clinician identify cognitively intact subjects that are at high risk to develop AD.

Gray matter characteristics associated with trait anxiety in older adults are moderated by depression.

BACKGROUND: Structural gray matter characteristics of anxiety remain unclear. The aim of this study was to assess the influence of current depressive symptoms and history of depression on the gray matter characteristics of trait anxiety. METHODS: Structural magnetic resonance imaging (MRI) data from 393 individuals aged 65 years or older were used. Regions of interest (ROIs) included the amygdala, anterior cingulate cortex (ACC), insula, orbitofrontal cortex (OFC), and temporal cortex. Trait anxiety was measured by the State-Trait Anxiety Inventory (STAI). Depression and depressive symptoms were measured using DSM-IV criteria and the Center for Epidemiological Studies Depression Scale (CESD). RESULTS: After adjustments for sociodemographics and health-related variables, anxiety had a significant influence on the gray matter characteristics in all cortical ROIs. First, in participants without depression antecedents, higher trait anxiety was associated with a larger cortical thickness in all cortical ROIs. Second, in participants with a previous history of depression, higher trait anxiety was associated with a smaller cortical thickness in all cortical ROIs. CONCLUSIONS: These results suggest that anxiety is related to cortical thickness differently in healthy older adults and in older adults with psychiatric antecedents. Anxiety associated with thinner cortical areas could reflect symptoms of a specific type of depression or a vulnerability to develop depression.