Influence of corpus callosum damage on cognition and physical disability in multiple sclerosis: a multimodal study.

Background Corpus callosum (CC) is a common target for multiple sclerosis (MS) pathology. We investigated the influence of CC damage on physical disability and cognitive dysfunction using a multimodal approach. Methods Twenty-one relapsing-remitting MS patients and 13 healthy controls underwent structural MRI and diffusion tensor of the CC (fractional anisotropy; mean diffusivity, MD; radial diffusivity, RD; axial diffusivity). Interhemisferic transfer of motor inhibition was assessed by recording the ipsilateral silent period (iSP) to transcranial magnetic stimulation. We evaluated cognitive function using the Brief Repeatable Battery and physical disability using the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC) z-score. Results The iSP latency correlated with physical disability scores (r ranged from 0.596 to 0.657, P values from 0.004 to 0.001), and with results of visual memory (r = −0.645, P = 0.002), processing speed (r = −0.51, P = 0.018) and executive cognitive domain tests (r = −0.452, P = 0.039). The area of the rostrum correlated with the EDSS (r = −0.442, P = 0.045). MD and RD correlated with cognitive performance, mainly with results of visual and verbal memory tests (r ranged from −0.446 to −0.546, P values from 0.048 to 0.011). The iSP latency correlated with CC area (r = −0.345, P = 0.049), volume (r = −0.401, P = 0.002), MD (r = 0.404, P = 0.002) and RD (r = 0.415, P = 0.016). Conclusions We found evidence for structural and microstructural CC abnormalities associated with impairment of motor callosal inhibitory conduction in MS. CC damage may contribute to cognitive dysfunction and in less extent to physical disability likely through a disconnection mechanism

Tècniques de reconstrucció d'imatges en SPECT

L'espectacular avenç en la tecnologia mèdica que s'ha produït en els darrers anys, i l'augment de potencia de càlcul dels ordinadors, han generalitzat la utilització de tècniques cada vegada més sofisticades en l'àmbit del diagnòstic per la imatge. En l'actualitat disposem de tècniques d'obtenció d'imatges biomèdiques que, en aportar informació complementària morfològica i funcional, estan augmentant la capacitat de diagnòstic mitjançant tècniques no invasives. Com a exemple cal destacar la tomografia per ordinador de raigs X (SO) -impròpiament coneguda com a TC o tomografia computeritzada-, l'ecografia, la ressonància magnetita nuclear (RMN) i la tomografia d'emissió de fotons, en les dues vessants, emissió de fotó únic (SPECT, single photon emission computed tomography) o emissió de dos fotons d'aniquilació (PET, positron emission tomography). Així, les radiografies convencionals d'atenuació de raigs X, o les gammagrafies planars obtingudes per emissió de radiació γ d'un traçador, s'han vist complementades amb imatges transversals del cos humà, obtingudes a partir de projeccions bidimensionals

Birth weight and adult IQ, but not anxious-depressive psychopathology, are associated with cortical surface area: a study in twins.

Background Previous research suggests that low birth weight (BW) induces reduced brain cortical sur- face area (SA) which would persist until at least early adulthood. Moreover, low BW has been linked to psychiatric disorders such as depression and psychological distress, and to altered neurocognitive profiles. Aims We present novel findings obtained by analysing high-resolution structural MRI scans of 48 twins; specifically, we aimed: i) to test the BW-SA association in a middle-aged adult sam- ple; and ii) to assess whether either depression/anxiety disorders or intellectual quotient (IQ) influence the BW-SA link, using a monozygotic (MZ) twin design to separate environ- mental and genetic effects. Results Both lower BW and decreased IQ were associated with smaller total and regional cortical SA in adulthood. Within a twin pair, lower BW was related to smaller total cortical and regional SA. In contrast, MZ twin differences in SA were not related to differences in either IQ or depression/anxiety disorders

Influence of corpus callosum damage on cognition and physical disability in multiple sclerosis: a multimodal study.

Background Corpus callosum (CC) is a common target for multiple sclerosis (MS) pathology. We investigated the influence of CC damage on physical disability and cognitive dysfunction using a multimodal approach. Methods Twenty-one relapsing-remitting MS patients and 13 healthy controls underwent structural MRI and diffusion tensor of the CC (fractional anisotropy; mean diffusivity, MD; radial diffusivity, RD; axial diffusivity). Interhemisferic transfer of motor inhibition was assessed by recording the ipsilateral silent period (iSP) to transcranial magnetic stimulation. We evaluated cognitive function using the Brief Repeatable Battery and physical disability using the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC) z-score. Results The iSP latency correlated with physical disability scores (r ranged from 0.596 to 0.657, P values from 0.004 to 0.001), and with results of visual memory (r = −0.645, P = 0.002), processing speed (r = −0.51, P = 0.018) and executive cognitive domain tests (r = −0.452, P = 0.039). The area of the rostrum correlated with the EDSS (r = −0.442, P = 0.045). MD and RD correlated with cognitive performance, mainly with results of visual and verbal memory tests (r ranged from −0.446 to −0.546, P values from 0.048 to 0.011). The iSP latency correlated with CC area (r = −0.345, P = 0.049), volume (r = −0.401, P = 0.002), MD (r = 0.404, P = 0.002) and RD (r = 0.415, P = 0.016). Conclusions We found evidence for structural and microstructural CC abnormalities associated with impairment of motor callosal inhibitory conduction in MS. CC damage may contribute to cognitive dysfunction and in less extent to physical disability likely through a disconnection mechanism

Genotypic effects of APOE-ε4 on resting-state connectivity in cognitively intact individuals support functional brain compensation

The investigation of resting-state functional connectivity (rsFC) in asymptomatic individuals at genetic risk for Alzheimer's disease (AD) enables discovering the earliest brain alterations in preclinical stages of the disease. The APOE-ε4 variant is the major genetic risk factor for AD, and previous studies have reported rsFC abnormalities in carriers of the ε4 allele. Yet, no study has assessed APOE-ε4 gene-dose effects on rsFC measures, and only a few studies included measures of cognitive performance to aid a clinical interpretation. We assessed the impact of APOE-ε4 on rsFC in a sample of 429 cognitively unimpaired individuals hosting a high number of ε4 homozygotes (n = 58), which enabled testing different models of genetic penetrance. We used independent component analysis and found a reduced rsFC as a function of the APOE-ε4 allelic load in the temporal default-mode and the medial temporal networks, while recessive effects were found in the extrastriate and limbic networks. Some of these results were replicated in a subsample with negative amyloid markers. Interaction with cognitive data suggests that such a network reorganization may support cognitive performance in the ε4-homozygotes. Our data indicate that APOE-ε4 shapes the functional architecture of the resting brain and favor the idea of a network-based functional compensation.The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/GN17/50300004 and the Alzheimer’s Association and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa-17-519007). Additional support has been received from the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant no. 2017-SGR-892. JDG is supported by the Spanish Ministry of Science and Innovation (RYC-2013-13054). MSC receives funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 948677) and the Instituto de Salud Carlos III (PI19/00155). KB is supported by the Swedish Research Council (#2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), the National Institute of Health (NIH), USA, (grant #1R01AG068398-01), and the Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 860197 (MIRIADE), and the UK Dementia Research Institute at UCL

Episodic memory and executive functions in cognitively healthy individuals display distinct neuroanatomical correlates which are differentially modulated by aging

The neuroanatomical bases of episodic memory (EM) and executive functions (EFs) have been widely addressed in patients with brain damage and in individuals with neurologic disorders. These studies reported that larger brain structures support better outcomes in both cognitive domains, thereby supporting the "bigger is better" account. However, relatively few studies have explored the cerebral morphological properties underlying EM and EFs in cognitively healthy individuals and current findings indicate no unitary theoretical explanation for the structure-function relationship. Moreover, existing studies have typically restricted the analyses to a priori defined regions of interest. Here we conducted unbiased voxel-wise analysis of the associations between regional gray as well as white matter volumes (GMv; WMv) and performance in both cognitive domains in a sample of 463 cognitively intact individuals. We found that efficiency in EM was predicted by lower GMv in brain areas belonging to the default-mode network (DMN). By contrast, EFs performance was predicted by larger GMv in a distributed set of regions, which overlapped with the executive control network (ECN). Volume of white matter bundles supporting both cross-cortical and interhemispheric connections was positively related to processing speed. Furthermore, aging modulated the relationship between regional volumes and cognitive performance in several areas including the hippocampus and frontal cortex. Our data extend the critical role of the DMN and ECN by showing that variability in their morphological properties, and not only their activation patterns, affects EM and EFs, respectively. Moreover, our finding that aging reverts these associations supports previously advanced theories of cognitive neurodevelopment

Perivascular spaces are associated with tau pathophysiology and synaptic dysfunction in early Alzheimer's continuum

Background: Perivascular spaces (PVS) have an important role in the elimination of metabolic waste from the brain. It has been hypothesized that the enlargement of PVS (ePVS) could be affected by pathophysiological mechanisms involved in Alzheimer's disease (AD), such as abnormal levels of CSF biomarkers. However, the relationship between ePVS and these pathophysiological mechanisms remains unknown. Objective: We aimed to investigate the association between ePVS and CSF biomarkers of several pathophysiological mechanisms for AD. We hypothesized that ePVS will be associated to CSF biomarkers early in the AD continuum (i.e., amyloid positive cognitively unimpaired individuals). Besides, we explored associations between ePVS and demographic and cardiovascular risk factors. Methods: The study included 322 middle-aged cognitively unimpaired participants from the ALFA + study, many within the Alzheimer's continuum. NeuroToolKit and Elecsys® immunoassays were used to measure CSF Aβ42, Aβ40, p-tau and t-tau, NfL, neurogranin, TREM2, YKL40, GFAP, IL6, S100, and α-synuclein. PVS in the basal ganglia (BG) and centrum semiovale (CS) were assessed based on a validated 4-point visual rating scale. Odds ratios were calculated for associations of cardiovascular and AD risk factors with ePVS using logistic and multinomial models adjusted for relevant confounders. Models were stratified by Aβ status (positivity defined as Aβ42/40 < 0.071). Results: The degree of PVS significantly increased with age in both, BG and CS regions independently of cardiovascular risk factors. Higher levels of p-tau, t-tau, and neurogranin were significantly associated with ePVS in the CS of Aβ positive individuals, after accounting for relevant confounders. No associations were detected in the BG neither in Aβ negative participants. Conclusions: Our results support that ePVS in the CS are specifically associated with tau pathophysiology, neurodegeneration, and synaptic dysfunction in asymptomatic stages of the Alzheimer's continuum.The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/GN17/50300004 and the Alzheimer’s Association and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa-17–519007). Additional support has been received from the Health Department of the Catalan Government (Health Research and Innovation Strategic Plan (PERIS) 2016–2020 grant# SLT002/16/00201) and the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant no. 2017-SGR-892. All CRG authors acknowledge the support of the Spanish Ministry of Science, Innovation and Universities to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme/Generalitat de Catalunya. NV-T is funded by a post-doctoral grant, Juan de la Cierva Programme (FJC2018-038085-I), Ministry of Science and Innovation– Spanish State Research Agency. MS-C received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie action grant agreement No 752310, and currently receives funding from Instituto de Salud Carlos III (PI19/00155) and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva Programme grant IJC2018-037478-I). EMAU is supported by the Spanish Ministry of Science, Innovation and Universities—Spanish State Research Agency (RYC2018-026053-I). OGR is supported by the Spanish Ministry of Science, Innovation and Universities (FJCI-2017–33437). JDG is supported by the Spanish Ministry of Science and Innovation (RYC-2013–13054). KB is supported by the Swedish Research Council (#2017–00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809–2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466–236). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018–02532), the European Research Council (#681712), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-720931), the ADDF, USA (#201809–2016862), and the UK Dementia Research Institute at UCL