cerebral atrophy

BACKGROUND: Recent genetic evidence supports that circulating biochemical and metabolic traits (BMTs) play a causal role in Alzheimer's disease (AD), which might be mediated by changes in brain structure. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between blood BMTs, brain image-derived phenotypes (IDPs) and AD. METHODS: Utilizing the genetic variants associated with 760 blood BMTs and 172 brain IDPs as the exposure and the latest AD summary statistics as the outcome, we analyzed the causal relationship between blood BMTs and brain IDPs and AD by using a two-sample Mendelian randomization (MR) method...

BACKGROUND: Atrial Fibrillation (AF) is a common cause of ischemic stroke (IS), and is associated with cognitive impairment in the general population. We aimed to compare the prevalence of preexisting cognitive impairment between IS patients with and without AF, and to assess whether prior brain damage could contribute to the observed differences. METHODS: Patients with acute IS were prospectively identified from the population-based Dijon Stroke Registry, France...

OBJECTIVE: Chronic cerebral hypoperfusion (CCH) is a common cause of brain dysfunction. As a microRNA (also known as miRNAs or miRs), miR-30a-5p participates in neuronal damage and relates to ferroptosis. We explored the in vivo and in vitro effects and functional mechanism of miR-30a-5p in CCH-triggered cognitive impairment through the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. METHODS: After 1 month of CCH modeling through bilateral common carotid artery stenosis, mice were injected with 2μL antagomir (also known as anti-miRNAs) miR-30a-5p, with cognitive function evaluated by Morris water maze and novel object recognition tests...

The Dyke-Davidoff-Masson syndrome (DDMS) is an uncommon neurological disorder whose prevalence is not yet known. There have only been 21 adult manifestations of this rare brain disorder, out of around 100 cases previously documented. Diagnosis is challenging because of the complexity of radiological findings and clinical symptoms, which include ventricle dilation, hypertrophy of the cranial bones, increased pneumatization of the sinuses, and cerebral hemisphere atrophy. It can be inherited or acquired from infections, brain hemorrhage, and hypoxia during pregnancy...

Sickle cell disease (SCD) patients are at higher risk of developing silent cerebral infarcts and overt stroke, which may reflect cognitive impairment, functional limitations, and worse quality of life. The cognitive function of Brazilian adult SCD patients ( n  = 124; 19-70 years; 56 men; 79 SS, 28 SC, 10 S/β0 , 7 S/β+ ) was screened through Montreal Cognitive Assessment (MoCA) and correlated the results with possible predictive factors for test performance, including sociocultural, clinical, laboratory data and brain imaging...

Apraxia localization has relied on voxel-based, lesion-symptom mapping studies in left hemisphere stroke patients. Studies on the neural substrates of different manifestations of apraxia in neurodegenerative disorders are scarce. The primary aim of this study was to look into the neural substrates of different manifestations of apraxia in a cohort of corticobasal syndrome patients (CBS) by use of cortical thickness. Twenty-six CBS patients were included in this cross-sectional study. The Goldenberg apraxia test (GAT) was applied...

BACKGROUND AND OBJECTIVES: Hexokinase 1 (encoded by HK1 ) catalyzes the first step of glycolysis, the adenosine triphosphate-dependent phosphorylation of glucose to glucose-6-phosphate. Monoallelic HK1 variants causing a neurodevelopmental disorder (NDD) have been reported in 12 individuals. METHODS: We investigated clinical phenotypes, brain MRIs, and the CSF of 15 previously unpublished individuals with monoallelic HK1 variants and an NDD phenotype. RESULTS: All individuals had recurrent variants likely causing gain-of-function, representing mutational hot spots...

Biallelic TOE1 variants can cause pontocerebellar hypoplasia type 7 (PCH7), a condition characterized by pontocerebellar hypoplasia with genital abnormality. TOE1 is a 3'-exonuclese for 3'-end maturation in small nuclear RNA. TOE1 pathogenic variants have been reported at the DEDD catalytic domain and zinc finger motif. Here, we describe a PCH7 patient with novel compound heterozygous TOE1 variants and a detailed clinical course. The patient was a 3-year-old female and showed developmental delay without cerebellar ataxic behavior...

BACKGROUND: White matter hyperintensities (WMHs) represent diffuse small vessel disease implicating the cardiac, systemic, and cerebral vasculatures. As the brain may be the end-organ of cumulative vascular disease, and higher education is protective of both cardiovascular and brain health, we aim to clarify their intertwining relationships. METHODS: We evaluated participants (mean age = 64) from the UK Biobank with neuroimaging measures of WMHs, left ventricular ejection fraction (LVEF) quantified using cardiovascular MRI, and arterial stiffness index (ASI) quantified using finger photoplethysmography...

This report presents a case of Alexander disease showing clinical characteristics mimicking progressive supranuclear palsy (PSP). A 67-year-old woman complaining of motor disturbance exhibited severe atrophy of medulla, spinal cord, and midbrain tegmentum, as well as periventricular hyperintensity on cerebral MRI. Genetic analysis identified a novel in-frame deletion/insertion mutation in the exon 3 of the GFAP gene. Interestingly, neurological findings and decreased striatal uptake in dopamine transporter SPECT were suggestive of PSP...

Cellular senescence, characterized by expressing the cell cycle inhibitory protein p21/CDKN1A, is evident in driving age-related diseases. Senescent cells play a crucial role in the initiation and progression of tau-mediated pathology, suggesting that targeting cell senescence offers a therapeutic potential for treating tauopathy associated diseases. This study focuses on identifying non-invasive biomarkers and validating their responses to a well-characterized senolytic therapy combining dasatinib and quercetin (D+Q), in a widely used tauopathy mouse model, PS19...

BACKGROUND: Multiple sclerosis (MS) has a complex pathophysiology which depends on many endogenous and exogenous factors. Vitamin D involvement has been largely studied in MS. The large distribution of the vitamin D receptor (VDR) in different immune cells is suggestive of an immunomodulatory role. The VDR gene polymorphisms have been proposed as potential risk factors for MS development or evolution with non-conclusive results. METHODS AND RESULTS: We conducted a cross-sectional study including patients ≥ 18 years, with a diagnosis of relapsing remitting MS according to the McDonald Criteria and having a minimum follow-up period of one year after starting a disease modifying therapy...

INTRODUCTION: Cerebral small vessel disease (SVD) and amyloid beta (Aβ) pathology frequently co-exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood. METHODS: In a unique cohort of mixed Alzheimer's disease and moderate-severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aβ, as assessed by 18 F-AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape...

BACKGROUND: This case report presents a patient with progressive memory loss and choreiform movements. CASE PRESENTATION: Neuropsychological tests indicated multi-domain amnestic mild cognitive impairment (aMCI), and neurological examination revealed asymmetrical involuntary hyperkinetic movements. Imaging studies showed severe left-sided atrophy and hypometabolism in the left frontal and temporoparietal cortex. [18 F]Flortaucipir PET exhibited moderately increased tracer uptake in hypometabolic areas...

The trafficking protein particle (TRAPP) complex is a multisubunit protein complex that functions as a tethering factor involved in intracellular trafficking. TRAPPC11, a crucial subunit of this complex, is associated with pathogenic variants that cause a spectrum of disease, which can range from a limb girdle muscular dystrophy (LGMD) to developmental disability with muscle disease, movement disorder and global developmental delay (GDD)/intellectual disability (ID), or even a congenital muscular dystrophy (CMD)...

Arterial stiffness (arteriosclerosis) has been linked to heightened risks for cognitive decline, and ultimately for Alzheimer's disease and other forms of dementia. Importantly, neurovascular outcomes generally vary according to one's biological sex. Here, capitalizing on a large sample of participants with neuroimaging and behavioral data ( N = 203, age range = 18-87 years), we aimed to provide support for a hierarchical model of neurocognitive aging, which links age-related declines in cerebrovascular health to the rate of cognitive decline via a series of intervening variables, such as white matter integrity...

MEGDEL syndrome, a rare autosomal recessive disorder characterized by 3-methylglutaconic aciduria, deafness, encephalopathy, and Leigh-like syndrome, results from mutations in the SERAC1 gene. This case report explores the clinical presentation, diagnostic challenges, and genetic findings of an 11-year-old boy with MEGDEL syndrome at a tertiary care center in Saudi Arabia. The patient, born to consanguineous parents, presented with developmental delay, cerebral palsy, intellectual disability, and seizures. Diagnostic evaluation at 15 months revealed 3-methylglutaconic aciduria, and subsequent genetic testing through whole exome sequencing confirmed a rare homozygous deletion variant in the SERAC1 gene...

INTRODUCTION: Although cerebral edema is common following traumatic brain injury (TBI), its formation and progression are poorly understood. This is especially true for the mild TBI population, who rarely undergo magnetic resonance imaging (MRI) studies, which can pick up subtle structural details not visualized on computed tomography, in the first few days after injury. This study aimed to visually classify and quantitatively measure edema progression in relation to traumatic microbleeds (TMBs) in a cohort of primarily mild TBI patients up to 30 days after injury...

Biallelic pathogenic variants in ZNF335 are one of the genetic causes of microcephaly, reported only in the past decade. It regulates neural progenitor proliferation and neurogenesis by interacting with a H3K4 methyltransferase complex. Biallelic pathogenic ZNF335 variants predispose to neuronal cell death and aberrant differentiation, thus causing secondary microcephaly. These neurodevelopmental anomalies lead to imaging findings in the cortex, posterior fossa, and basal ganglia. We report an individual of Nepalese ancestry with a novel homozygous ZNF335 variant (c...

BACKGROUND: The ASNS (ASNS, MIM 108370) gene variations are responsible for asparagine synthetase deficiency (ASNSD, MIM 615574), a very rare autosomal recessive disease characterized by cerebral anomalies. These patients have congenital microcephaly, progressive encephalopathy, severe intellectual disability, and intractable seizures. METHOD: Clinical characteristics of the patient were collected. Exome sequencing was used for the identification of variants. Sanger sequencing was used to confirm the variant in the target region...