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1.
Cell Rep Med ; 5(5): 101529, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38703765

RESUMEN

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.


Asunto(s)
Estudio de Asociación del Genoma Completo , Cabeza , Neoplasias , Humanos , Cabeza/anatomía & histología , Neoplasias/genética , Neoplasias/patología , Femenino , Masculino , Polimorfismo de Nucleótido Simple/genética , Variación Genética , Tamaño de los Órganos/genética , Transducción de Señal/genética , Adulto , Predisposición Genética a la Enfermedad
2.
Eur J Epidemiol ; 39(4): 409-417, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38190014

RESUMEN

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.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Demencia , Diabetes Mellitus Tipo 2 , Imagen por Resonancia Magnética , Análisis de Mediación , Humanos , Femenino , Masculino , Anciano , Demencia/etiología , Demencia/epidemiología , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/patología , Diabetes Mellitus Tipo 2/complicaciones , Factores de Riesgo , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Biomarcadores/sangre , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neurodegenerativas/epidemiología , Anciano de 80 o más Años
3.
Br J Nutr ; 131(3): 512-520, 2024 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-37694377

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Queso , Humanos , Anciano , Animales , Productos Lácteos , Leche , Encéfalo/diagnóstico por imagen , Dieta
4.
Alzheimers Dement (Amst) ; 15(3): e12460, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37745892

RESUMEN

INTRODUCTION: Alzheimer's disease is associated with sleep disturbances and accumulation of cerebral amyloid beta. The objective was to examine whether actigraphy-detected sleep parameters might be biomarkers for early amyloid burden. METHODS: Participants underwent a week of actigraphy and an amyloid positron emission tomography (PET) scan. Sleep duration and continuity disruption (sleep fragmentation and nocturnal awakenings) were extracted and compared between amyloid-positive and amyloid-negative participants. Then multiple linear regressions were used between mean or night-to-night intra-individual variability (standard deviation) of sleep parameters and brain amyloid burden in a voxel-wise analysis. RESULTS: Eighty-six subjects were included (80.3 ± 5.4 years; 48.8% of women). Amyloid-positive participants had a higher variability of sleep fragmentation compared to amyloid-negative participants. This parameter was associated with a higher amyloid burden in the frontal and parietal regions, and in the precuneus, in the whole sample. DISCUSSION: This study highlights the relevance of using variability in sleep continuity as a potential biomarker of early amyloid pathogenesis.

5.
Alzheimers Dement ; 19(8): 3283-3294, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36749884

RESUMEN

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.


Asunto(s)
Afasia , Demencia Frontotemporal , Humanos , Demencia Frontotemporal/diagnóstico por imagen , Imagen por Resonancia Magnética , Atrofia , Lenguaje
6.
Transl Stroke Res ; 14(2): 185-192, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35437660

RESUMEN

Microstructural changes after an ischemic stroke (IS) have mainly been described in white matter. Data evaluating microstructural changes in gray matter (GM) remain scarce. The aim of the present study was to evaluate the integrity of GM on longitudinal data using mean diffusivity (MD), and its influence on post-IS cognitive performances. A prospective study was conducted, including supra-tentorial IS patients without pre-stroke disability. A cognitive assessment was performed at baseline and 1 year, including a Montreal Cognitive Assessment, an Isaacs set test, and a Zazzo cancelation task (ZCT): completion time and number of errors. A 3-T brain MRI was performed at the same two time-points, including diffusion tensor imaging for the assessment of GM MD. GM volume was also computed, and changes in GM volume and GM MD were evaluated, followed by the assessment of the relationship between these structural changes and changes in cognitive performances. One hundred and four patients were included (age 68.5 ± 21.5, 38.5% female). While no GM volume loss was observed, GM MD increased between baseline and 1 year. The increase of GM MD in left fronto-temporal regions (dorsolateral prefrontal cortex, superior and medial temporal gyrus, p < 0.05, Threshold-Free Cluster Enhancement, 5000 permutations) was associated with an increase time to complete ZCT, regardless of demographic confounders, IS volume and location, GM, and white matter hyperintensity volume. GM integrity deterioration was thus associated with processing speed slowdown, and appears to be a biomarker of cognitive frailty. This broadens the knowledge of post-IS cognitive impairment mechanisms.


Asunto(s)
Accidente Cerebrovascular Isquémico , Sustancia Blanca , Humanos , Femenino , Masculino , Sustancia Gris/diagnóstico por imagen , Imagen de Difusión Tensora , Velocidad de Procesamiento , Estudios Prospectivos , Sustancia Blanca/diagnóstico por imagen , Encéfalo/diagnóstico por imagen
7.
Psychol Aging ; 37(8): 913-928, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36174174

RESUMEN

The age-related positivity effect is the tendency of older adults to preferentially process positive information over negative information when compared to younger adults (e.g., Reed & Carstensen, 2012). The aim of the study was to determine whether common and/or distinct mechanisms underlie the age-related positivity effect in lexical access and episodic memory. Fifty young and 50 older adults successively performed a progressive demasking task incorporating memory instructions, an immediate free recall task, a memory recognition task, and delayed free recalls at 20 min and 7 days. The materials included 60 words that varied in emotional valence (positive, neutral, negative) and arousal (low, high). The results revealed that distinct processes underlie the age-related positivity effect in lexical access and episodic memory. In progressive demasking, this effect emerged for both low- and high-arousal words, suggesting that it depends on automatic processes. In immediate and delayed free recall and recognition, this effect emerged for low-arousal words only, suggesting that it depends on more controlled processes. Moreover, in older adults, positivity scores correlated with well-being scores for episodic memory. These results are discussed in relation to affective aging theories. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Asunto(s)
Memoria Episódica , Humanos , Anciano , Envejecimiento/psicología , Emociones , Reconocimiento en Psicología , Memoria a Corto Plazo
8.
Brain Commun ; 4(3): fcac109, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35592489

RESUMEN

The chronological progression of brain atrophy over decades, from pre-symptomatic to dementia stages, has never been formally depicted in Alzheimer's disease. This is mainly due to the lack of cohorts with long enough MRI follow-ups in cognitively unimpaired young participants at baseline. To describe a spatiotemporal atrophy staging of Alzheimer's disease at the whole-brain level, we built extrapolated lifetime volumetric models of healthy and Alzheimer's disease brain structures by combining multiple large-scale databases (n = 3512 quality controlled MRI from 9 cohorts of subjects covering the entire lifespan, including 415 MRI from ADNI1, ADNI2 and AIBL for Alzheimer's disease patients). Then, we validated dynamic models based on cross-sectional data using external longitudinal data. Finally, we assessed the sequential divergence between normal aging and Alzheimer's disease volumetric trajectories and described the following staging of brain atrophy progression in Alzheimer's disease: (i) hippocampus and amygdala; (ii) middle temporal gyrus; (iii) entorhinal cortex, parahippocampal cortex and other temporal areas; (iv) striatum and thalamus and (v) middle frontal, cingular, parietal, insular cortices and pallidum. We concluded that this MRI scheme of atrophy progression in Alzheimer's disease was close but did not entirely overlap with Braak staging of tauopathy, with a 'reverse chronology' between limbic and entorhinal stages. Alzheimer's disease structural progression may be associated with local tau accumulation but may also be related to axonal degeneration in remote sites and other limbic-predominant associated proteinopathies.

9.
Hum Brain Mapp ; 43(10): 3270-3282, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35388950

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/patología , Atrofia/diagnóstico por imagen , Atrofia/patología , Disfunción Cognitiva/patología , Progresión de la Enfermedad , Hipocampo/patología , Humanos , Longevidad , Imagen por Resonancia Magnética/métodos
10.
Transl Stroke Res ; 13(5): 716-724, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35106712

RESUMEN

Normal-appearing white matter (NAWM) is a hub of plasticity, but data relating to its influence on post-ischemic stroke (IS) outcome remain scarce. The aim of this study was to evaluate the relationship between NAWM integrity and cognitive outcome after an IS. A longitudinal study was conducted including supra-tentorial IS patients. A 3-Tesla brain MRI was performed at baseline and 1 year, allowing the analyses of mean fractional anisotropy (FA) and mean diffusivity (MD) in NAWM masks, along with the volume of white matter hyperintensities (WMH) and IS. A Montreal Cognitive Assessment (MoCA), an Isaacs set test, and a Zazzo's cancellation task were performed at baseline, 3 months and 1 year. Mixed models were built, followed by Tract-based Spatial Statistics (TBSS) analyses. Ninety-five patients were included in the analyses (38% women, median age 69 ± 20). FA significantly decreased, and MD significantly increased between baseline and 1 year, while cognitive scores improved. Patients who decreased their NAWM FA more over the year had a slower cognitive improvement on MoCA (ß = - 0.11, p = 0.05). The TBSS analyses showed that patients who presented the highest decrease of FA in various tracts of white matter less improved their MoCA performances, regardless of WMH and IS volumes, demographic confounders, and clinical severity. NAWM integrity deteriorates over the year after an IS, and is associated with a cognitive recovery slowdown. The diffusion changes recorded here in patients starting with an early preserved white matter structure could have long term impact on cognition.


Asunto(s)
Accidente Cerebrovascular Isquémico , Leucoaraiosis , Sustancia Blanca , Anciano , Anciano de 80 o más Años , Cognición , Imagen de Difusión Tensora , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Sustancia Blanca/diagnóstico por imagen
11.
Artículo en Inglés | MEDLINE | ID: mdl-34583917

RESUMEN

A growing number of studies have shown that when compared to younger adults, older adults are better at recalling positive information than negative information. However, it is not yet clear whether this age-related positivity effect relies on a greater ability to recall positive information or on a decreased ability to recall negative information. We therefore aimed to study the specific mechanisms underlying the age-related positivity effect using different memory tasks. We used an emotional word memory paradigm including immediate free recall, recognition, and delayed free recall tasks. Forty-five young adults (m = 20.0 years) and 45 older adults (m = 69.2 years) participated, all of whom were native French speakers. Thirty-six French low-arousal words (12 positve, 12, negative, 12 neutral) were selected from an emotional lexical database (Gobin et al. 2017) and divided into three equal groups of positive, neutral and negative terms. For the recognition task, 36 new words were selected. The results show that the age-related positivity effect specifically depended on a decrease in negativity preference (i.e., the comparison between negative and neutral words) in older adults, in comparison with younger adults, both in the immediate and delayed free recall tasks. In these tasks, younger adults recalled more negative than neutral words, whereas there was no difference in older adults. During the recognition task, no age-related positivity effect was observed. The results also show that, for the immediate recall task, the greater the memory ability of older adults, the lower their negativity preference. This correlation was not significant in the delayed recall task. These results suggest that, when compared with younger adults, older adults disengage from processing negative words that require costly cognitive processes. A low negativity preference indicates that memory abilities are well-maintained. The results are discussed within the framework of socio-emotional selectivity theory.

12.
Transl Psychiatry ; 11(1): 414, 2021 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-34333531

RESUMEN

While previous studies suggest the implication of herpes simplex virus (HSV) in the onset of Alzheimer's disease (AD), no study has investigated its association with early neuroimaging markers of AD. In the Three-City and the AMI cohorts, the associations between HSV infection and (i) hippocampal volume (n = 349), (ii) white matter alterations in the parahippocampal cingulum and fornix using diffusion tensor imaging (n = 260), and (iii) incidence of AD (n = 1599) were assessed according to APOE4 status. Regardless of APOE4 status, infected subjects presented (i) significantly more microstructural alterations of the parahippocampal cingulum and fornix, (ii) lower hippocampal volumes only when their anti-HSV IgG level was in the highest tercile-reflecting possibly more frequent reactivations of the virus (p = 0.03 for subjects with a high anti-HSV IgG level while there was no association for all infected subjects, p = 0.19), and (iii) had no increased risk of developing AD. Nevertheless, among APOE4 carriers, infected subjects presented lower hippocampal volumes, although not significant (p = 0.09), and a two or three times higher risk of developing AD (adjusted Hazard ratio (aHR) = 2.72 [1.07-6.91] p = 0.04 for infected subjects and aHR = 3.87 [1.45-10.28] p = 0.007 for infected subjects with an anti-HSV IgG level in the highest tercile) while no association was found among APOE4 noncarriers. Our findings support an association between HSV infection and AD and a potential interaction between HSV status and APOE4. This reinforces the need to further investigate the infectious hypothesis of AD, especially the associated susceptibility factors and the possibility of preventive treatments.


Asunto(s)
Enfermedad de Alzheimer , Herpes Simple , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/epidemiología , Imagen de Difusión Tensora , Herpes Simple/epidemiología , Humanos , Incidencia , Simplexvirus
14.
Cerebrovasc Dis ; 50(4): 456-463, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33827075

RESUMEN

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.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Cognición , Disfunción Cognitiva/etiología , Accidente Cerebrovascular Isquémico/etiología , Imagen por Resonancia Magnética , Anciano , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/psicología , Diagnóstico Precoz , Femenino , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/psicología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Recuperación de la Función , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad
15.
Stroke ; 52(5): 1741-1750, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33657856

RESUMEN

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.


Asunto(s)
Trastornos Cerebrovasculares/patología , Hipocampo/patología , Sustancia Blanca/patología , Anciano , Atrofia/diagnóstico por imagen , Atrofia/patología , Trastornos Cerebrovasculares/diagnóstico por imagen , Estudios Transversales , Progresión de la Enfermedad , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Estudios Longitudinales , Espectroscopía de Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Sustancia Blanca/diagnóstico por imagen
16.
Brain ; 144(3): 909-923, 2021 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-33638639

RESUMEN

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.


Asunto(s)
Cerebelo/metabolismo , Cuerpo Estriado/metabolismo , Distonía Muscular Deformante/metabolismo , Proteínas de Transporte Vesicular de Acetilcolina/metabolismo , Adulto , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Chaperonas Moleculares/genética , Tomografía de Emisión de Positrones , Adulto Joven
17.
Clin Nutr ; 40(4): 2460-2463, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33558180

RESUMEN

BACKGROUND & AIMS: Carotenoids are vegetable pigments with neuroprotective properties. Clinical studies found efficacy of specific carotenoids on improving brain perfusion and functioning with aging. However, evidence of an effect on neurodegeneration, which may require longer follow-up period to observe, is more limited. Leveraging biomarkers from a large population-based cohort study of older adults, we investigated whether blood carotenoids were associated with atrophy of the medial temporal lobe (a biomarker of neurodegeneration in aging) over 10 years. METHODS: This study included 461 dementia-free participants from the Three-City Bordeaux study (aged ≥65) who had plasma carotenoids measured at baseline and up to three repeated brain imaging exams in the subsequent 10 years. RESULTS: In adjusted linear mixed models, each increase of 1 SD in plasma level of total carotenoids and of ß-carotene was associated with 0.02 cm3 (95% CI, 0.001-0.04; P = 0.04) and 0.02 cm3 (95% CI, 0.01-0.04; P = 0.008) smaller medial temporal lobe volume loss per year, respectively. CONCLUSIONS: Our results based on a unique long-term prospective evaluation of a neuroimaging biomarker suggest a beneficial role of carotenoids for the prevention of age-related neurodegeneration.


Asunto(s)
Carotenoides/sangre , Enfermedades Neurodegenerativas/epidemiología , Lóbulo Temporal/patología , Anciano , Atrofia , Femenino , Humanos , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Enfermedades Neurodegenerativas/prevención & control , Estudios Prospectivos , Lóbulo Temporal/diagnóstico por imagen , beta Caroteno/sangre
18.
Hum Brain Mapp ; 42(5): 1287-1303, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33385303

RESUMEN

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.


Asunto(s)
Cerebelo , Sustancia Gris , Desarrollo Humano/fisiología , Imagen por Resonancia Magnética/métodos , Sustancia Blanca , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cerebelo/anatomía & histología , Cerebelo/diagnóstico por imagen , Cerebelo/crecimiento & desarrollo , Niño , Preescolar , Femenino , Sustancia Gris/anatomía & histología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/crecimiento & desarrollo , Humanos , Procesamiento de Imagen Asistido por Computador , Lactante , Masculino , Persona de Mediana Edad , Sustancia Blanca/anatomía & histología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/crecimiento & desarrollo , Adulto Joven
19.
Heliyon ; 6(12): e05652, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33336093

RESUMEN

BACKGROUND: Alzheimer's Disease (AD) is a neurodegenerative disease characterized by progressive loss of memory and general decline in cognitive functions. Multi-modal imaging such as structural MRI and DTI provide useful information for the classification of patients on the basis of brain biomarkers. Recently, CNN methods have emerged as powerful tools to improve classification using images. NEW METHOD: In this paper, we propose a transfer learning scheme using Convolutional Neural Networks (CNNs) to automatically classify brain scans focusing only on a small ROI: e.g. a few slices of the hippocampal region. The network's architecture is similar to a LeNet-like CNN upon which models are built and fused for AD stage classification diagnosis. We evaluated various types of transfer learning through the following mechanisms: (i) cross-modal (sMRI and DTI) and (ii) cross-domain transfer learning (using MNIST) (iii) a hybrid transfer learning of both types. RESULTS: Our method shows good performances even on small datasets and with a limited number of slices of small brain region. It increases accuracy with more than 5 points for the most difficult classification tasks, i.e., AD/MCI and MCI/NC. COMPARISON WITH EXISTING METHODS: Our methodology provides good accuracy scores for classification over a shallow convolutional network. Besides, we focused only on a small region; i.e., the hippocampal region, where few slices are selected to feed the network. Also, we used cross-modal transfer learning. CONCLUSIONS: Our proposed method is suitable for working with a shallow CNN network for low-resolution MRI and DTI scans. It yields to significant results even if the model is trained on small datasets, which is often the case in medical image analysis.

20.
Geriatr Psychol Neuropsychiatr Vieil ; 18(4): 437-447, 2020 Dec 01.
Artículo en Francés | MEDLINE | ID: mdl-33289488

RESUMEN

A growing number of studies have shown that, compared to young adults, older adults better remember positive information than negative information. However, it is not clear whether this age-related positivity effect relies on an increase in positive information memory and/or on a decrease in negative information memory. Thus, we aimed to study the specific mechanisms underlying the age-related positivity effect in different memory tasks. To do so, we used an emotional word memory paradigm including immediate free recall, recognition and delayed free recall tasks. Forty-five young adults (m = 20.0 years) and 45 older adults (m = 69.2 years) native French speakers participated. Thirty-six low French words, including 12 negative (e.g. égout), 12 positive (e.g. lagune) and 12 neutral (e.g. notion) words were selected from an emotional lexical database (Gobin et al. 2017). For the recognition task, 36 new words were selected. The results showed that the age-related positivity effect specifically depended on a decrease in negativity preference (i.e. the comparison between negative and neutral words) in older adults, in comparison with young adults, both in immediate and delayed free recall tasks. Indeed, in these tasks, young adults recalled more negative than neutral words whereas there was no difference in older adults. In recognition task, no age-related positivity effect has been observed. Moreover, the results showed that, in immediate recall, the higher the older adults memory abilities, the lower their negativity preference. This correlation was not significant in delayed recall. These results suggest that, when compared with young adults, older adults disengage from negative words processing through costly cognitive processes. A small magnitude of negativity preference would indicate good maintenance of memory abilities. Results are discussed in the framework of the socioemotional selectivity theory.


Asunto(s)
Recuerdo Mental , Optimismo/psicología , Adolescente , Adulto , Factores de Edad , Anciano , Emociones , Femenino , Humanos , Masculino , Reconocimiento en Psicología , Adulto Joven
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