Search Results (8)

Alzheimer’s disease (AD) and vascular dementia (VaD) are the two most prevalent forms of dementia, sharing overlapping clinical features yet distinct pathophysiological mechanisms. While AD is primarily driven by amyloid-beta (Aβ) plaques and tau neurofibrillary tangles, VaD results from cerebrovascular pathology, including ischemic lesions and chronic hypoperfusion. However, accumulating evidence suggests that vascular dysfunction is a crucial contributor to both conditions, bridging neurodegenerative and cerebrovascular pathologies. In this review, we explore the interplay between AD and VaD, focusing on shared pathways such as blood–brain barrier (BBB) breakdown, neuroinflammation, and microvascular damage. Notably, cerebral microbleeds have emerged as a common feature in both AD and VaD, further linking vascular pathology to neurodegeneration. Microbleeding contributes to BBB disruption, iron deposition, and exacerbated oxidative stress, creating a vicious cycle that accelerates cognitive decline. We highlight the role of iron dysregulation as a key driver in AD, exacerbating Aβ accumulation, tau hyperphosphorylation, and ferroptosis. Conversely, bilirubin emerges as a molecule with theranostic potential, acting as both a biomarker and a neuroprotective agent due to its antioxidant and anti-inflammatory properties. Despite its protective role, bilirubin’s dysregulation under pathological conditions may contribute to oxidative damage and neurovascular dysfunction. In this context, the accumulation of iron from recurrent microbleeds may further disrupt bilirubin homeostasis, amplifying oxidative injury and inflammation. We propose a vascular hypothesis that integrates iron metabolism and bilirubin homeostasis, suggesting that their imbalance plays a central role in AD pathogenesis and worsening. Understanding the intricate molecular interplay between neurodegeneration and vascular dysfunction could provide novel insights into targeted interventions aimed at mitigating cognitive decline. Finally, we discuss the potential of bilirubin-based therapeutic strategies, including its role in counteracting oxidative stress and modulating neuroinflammatory pathways, offering promising avenues for future research and precision medicine in dementia. Full article

Iron overload in many brain regions is a common feature of aging and most neurodegenerative diseases. In this review, the causes, mechanisms, mathematical models, and possible therapies are summarized. Indeed, physiological and pathological conditions can be investigated using compartmental models mimicking iron trafficking across the blood–brain barrier and the Cerebrospinal Fluid-Brain exchange membranes located in the choroid plexus. In silico models can investigate the alteration of iron homeostasis and simulate iron concentration in the brain environment, as well as the effects of intracerebral iron chelation, determining potential doses and timing to recover the physiological state. Novel formulations of non-toxic nanovectors with chelating capacity are already tested in organotypic brain models and could be available to move from in silico to in vivo experiments. Full article

The aim of this review is to present evidence of the impact of ischemic changes in the blood–brain barrier on the maturation of post-ischemic brain neurodegeneration with features of Alzheimer’s disease. Understanding the processes involved in the permeability of the post-ischemic blood–brain barrier during recirculation will provide clinically relevant knowledge regarding the neuropathological changes that ultimately lead to dementia of the Alzheimer’s disease type. In this review, we try to distinguish between primary and secondary neuropathological processes during and after ischemia. Therefore, we can observe two hit stages that contribute to Alzheimer’s disease development. The onset of ischemic brain pathology includes primary ischemic neuronal damage and death followed by the ischemic injury of the blood–brain barrier with serum leakage of amyloid into the brain tissue, leading to increased ischemic neuronal susceptibility to amyloid neurotoxicity, culminating in the formation of amyloid plaques and ending in full-blown dementia of the Alzheimer’s disease type. Full article

The aim of this study was to evaluate the nailfold videocapillaroscopic examination results from patients with pseudoexfoliative glaucoma (XFG) and to assess the relationship between the results of this examination and the patient’s clinical status in the XFG group. Material and Methods: The studied group consisted of 39 Caucasian patients with XFG and 32 patients in a control group. The patients were classified into two subgroups: the hypertensive pseudoexfoliative glaucoma (hXFG) subgroup and the normotensive pseudoexfoliative glaucoma (nXFG) subgroup. The nailfold videocapillaroscopy (NVC) was performed on all participants. The results of each NVC were classified as having a normal or abnormal pattern. Results: There was no statistical difference between the results of an abnormal NVC pattern in the study group vs. the control group (p = 0.8773). Microhemorrhages were shown in 30.0% of patients with nXFG vs. the control group (6.25%) (p = 0.0520). Microhemorrhages tended to be more frequent in the XFG group (p = 0.1221). A prevalent number of tortuous capillaries was observed in hXFG patients with advanced glaucomatous neuropathy. Dilatation in the capillaries and microbleedings were observed in the group of patients with lower IOP values. Tortuosity in the capillaries was significantly more frequent in PEXG patients (XFG vs. control: p = 0.0386). No relationships between the results of NVC and age, c/d, BCVA, time of treatment, and visual field defect were found. Conclusions: Specific features of NVC examination differentiate nXFG from hXFG patients. Some capillaroscopic features may correlate with the patient’s clinical status of XFG. Full article

Patients with COVID-19 can require radiological examination, with chest CT being more frequent than neuro-imaging. The objective is to identify epidemiological, clinical and radiological factors considered as predictors of neurological involvement in patients with COVID-19 assessed by neuroimaging and to describe the neuroimaging findings. This retrospective study was performed with 232 consecutive confirmed COVID-19 patients, from two radiological units, which were divided into two groups: (1) those who underwent a brain CT/MRI scan (n = 35) versus (2) those who did not undergo the brain CT/MRI scan, but underwent only chest CT (n = 197). There was a statistically significant difference with associations regarding the COVID-19 brain scan group for: admission to ICU, greater severity of lung injuries, the use of a mechanical ventilator and sepsis. Statistical tendency was found for chronic renal failure and systemic arterial hypertension. Forty-percent of COVID-19 patients from the brain scan group were abnormal on brain CT and/or brain MRI (22.9% of the cases with bleeding or microbleeding, 8.6% with restricted diffusion lesions). One ischemic stroke case was associated with irregularity at the M1 segment of the right middle cerebral artery. There was a case of left facial nerve palsy with enhancement of the left geniculate ganglia. An analysis of the olfactory bulbs was possible in 12 brain MRIs and 100% had enhancement and/or microbleeding. In conclusion, a more severe COVID-19 disease from ICU, a more severe form of lung disease, the use of mechanical ventilator and sepsis were associated to the COVID-19 patients with neurological involvement who had undergone brain scans. Microvascular phenomenon was a frequent finding in the brain and olfactory bulbs evaluated by neuroimaging. Full article

Cardiovascular diseases (CVDs) and dementia are the leading causes of disability and mortality. Genetic connections between cardiovascular risk factors and dementia have not been elucidated. We conducted a scoping review and pathway analysis to reveal the genetic associations underlying both CVDs and dementia. In the PubMed database, literature was searched using keywords associated with diabetes mellitus, hypertension, dyslipidemia, white matter hyperintensities, cerebral microbleeds, and covert infarctions. Gene lists were extracted from these publications to identify shared genes and pathways for each group. This included high penetrance genes and single nucleotide polymorphisms (SNPs) identified through genome wide association studies. Most risk SNPs to both diabetes and dementia participate in the phospholipase C enzyme system and the downstream nositol 1,4,5-trisphosphate and diacylglycerol activities. Interestingly, AP-2 (TFAP2) transcription factor family and metabolism of vitamins and cofactors were associated with genetic variants that were shared by white matter hyperintensities and dementia, and by microbleeds and dementia. Variants shared by covert infarctions and dementia were related to VEGF ligand–receptor interactions and anti-inflammatory cytokine pathways. Our review sheds light on future investigations into the causative relationships behind CVDs and dementia, and can be a paradigm of the identification of dementia treatments. Full article

Background: Due to the difficulties in the definite diagnosis, data on brain imaging in pediatric patients with central nervous system (CNS)-invasive mold infection (IMD) are scarce. Our aim was to describe brain imaging abnormalities seen in immunocompromised children with CNS-IMD, and to analyze retrospectively whether specific imaging findings and sequences have a prognostic value. Methods: In a retrospective study of 19 pediatric patients with proven or probable CNS-IMD, magnetic resonance imaging (MRI)-findings were described and analyzed. The results were correlated with outcome, namely death, severe sequelae, or no neurological sequelae. Results: 11 children and 8 adolescents (11/8 with proven/probable CNS-IMD) were included. Seven of the patients died and 12/19 children survived (63%): seven without major neurological sequelae and five with major neurological sequelae. Multifocal ring enhancement and diffusion restriction were the most common brain MRI changes. Diffusion restriction was mostly seen at the core of the lesion. No patient with disease limited to one lobe died. Perivascular microbleeding seen on susceptibility weighted imaging (SWI) and/or gradient-echo/T2* images, as well as infarction, were associated with poor prognosis. Conclusions: The presence of infarction was related to poor outcome. As early microbleeding seems to be associated with poor prognosis, we suggest including SWI in routine diagnostic evaluation of immunocompromised children with suspected CNS-IMD. Full article

Cognitive decline and falls in the elderly are common and are often accepted as natural and inevitable by relatives and health care professionals, but frequently there are specific and treatable diseases that should be revealed. In our case, cerebral amyloid angiopathy-related inflammation (CAA-RI) was causative for neuro-psychiatric symptoms and worsening of gait in a 71 year-old man with recurrent falls and decline of gait and cognition. Cerebral amyloidangiopathy (CAA) is an important cause of cerebrovascular disorders in the elderly, characterized by leukoencephalopathy combined with lobar or small cortical hemorrhage due to amyloid deposition in cortical and leptomeningeal vessels. In several conditions, amyloid deposition can provoke inflammation or edema that lead to -normally reversible- encephalopathy. CAA-RI is then characterized by subacute neurobehavioral symptoms, headache, seizures or stroke-like signs. The first therapeutic option after confirming the diagnosis is treatment with glucocorticoids. Despite treatment with prednisolone, our patient could not regain his unrestricted mobility and self-help competence. Our report aims to sharpen awareness for CAA and its inflammatory form (CAA-RI) in healthcare professionals involved in medical care of the elderly and provide a short summary of this disease. Full article