Predicting amyloid-PET status in a memory clinic: The role of the novel antero-posterior index and visual rating scales.

INTRODUCTION: Visual rating scales are increasingly utilized in clinical practice to assess atrophy in crucial brain regions among patients with cognitive disorders. However, their capacity to predict Alzheimer's disease (AD)-related pathology remains unexplored, particularly within a heterogeneous memory clinic population. This study aims to assess the accuracy of a novel visual rating assessment, the antero-posterior index (API) scale, in predicting amyloid-PET status. Furthermore, the study seeks to determine the optimal cohort-based cutoffs for the medial temporal atrophy (MTA) and parietal atrophy (PA) scales and to integrate the main visual rating scores into a predictive model. METHODS: We conducted a retrospective analysis of brain MRI and high-resolution TC scans from 153 patients with cognitive disorders who had undergone amyloid-PET assessments due to suspected AD pathology in a real-world memory clinic setting. RESULTS: The API scale (cutoff ≥1) exhibited the highest accuracy (AUC = 0.721) among the visual rating scales. The combination of the cohort-based MTA and PA threshold with the API yielded favorable accuracy (AUC = 0.787). Analyzing a cohort of MCI/Mild dementia patients below 75 years of age, the API scale and the predictive model improved their accuracy (AUC = 0.741 and 0.813, respectively), achieving excellent results in the early-onset population (AUC = 0.857 and 0.949, respectively). CONCLUSION: Our study emphasizes the significance of visual rating scales in predicting amyloid-PET positivity within a real-world memory clinic. Implementing the novel API scale, alongside our cohort-based MTA and PA thresholds, has the potential to substantially enhance diagnostic accuracy.

Sleep Pathologies and Eating Disorders: A Crossroad for Neurology, Psychiatry and Nutrition.

The intricate connection between eating behaviors and sleep habits is often overlooked in clinical practice, despite their profound interdependence. Sleep plays a key role in modulating psychological, hormonal and metabolic balance and exerting an influence on food choices. Conversely, various eating disorders may affect sleep continuity, sometimes promoting the development of sleep pathologies. Neurologists, nutritionists and psychiatrists tend to focus on these issues separately, resulting in a failure to recognize the full extent of the clinical conditions. This detrimental separation can lead to underestimation, misdiagnosis and inappropriate therapeutic interventions. In this review, we aim to provide a comprehensive understanding of the tangled relationship between sleep, sleep pathologies and eating disorders, by incorporating the perspective of sleep experts, psychologists and psychiatrists. Our goal is to identify a practical crossroad integrating the expertise of all the involved specialists.

Non-alcoholic Wernicke's Encephalopathy mimicking neuromyelitis optica spectrum disorder in a young woman: a case report and literature review.

Wernicke's encephalopathy is an under-recognized life-threatening disease caused by thiamine (vitamin B1) deficiency. It has historically been related to chronic alcoholic intake but other causes of malnutrition, such as invasive gastric surgery and hyperemesis, have been linked to the onset of this illness over the years, often presenting with atypical clinical manifestations.  Herein we report a case of a young obese woman affected by non-alcoholic Wernicke's Encephalopathy following a minimally invasive gastrointestinal surgery. She showed an unusual clinical profile characterized by prominent subacute neuro-ophthalmological involvement which combined to her juvenile age, overweight condition and brain lesions, have made diagnosis challenging due to similarities with Neuromyelitis Optica Spectrum Disorder.   Our case underscores the relevance of prompt diagnosis in order to prevent the development of irreversible neuropathological changes and to avoid the use of a long-term immunosuppressive treatment.

Volumetric hippocampal changes in glioblastoma: a biomarker for neuroplasticity?

PURPOSE: The pleiotropic effect of gliomas on the development of cognitive disorders and structural brain changes has garnered increasing interest in recent years. While it is widely accepted that multimodal therapies for brain cancer can foster cognitive impairment, the direct effect of gliomas on critical cognitive areas before anti-tumor therapies is still controversial. In this study, we focused on the effect of IDH1 wild-type glioblastoma on the human hippocampus volume. METHODS: We carried out a case-control study using voxel-based morphometry assessment, analyzed with the Computational Anatomy Toolbox software. Glioblastoma diagnosis was performed according to the latest 2021 WHO classification. Due to stringent inclusion criteria, 15 patients affected by IDH1 wild type glioblastoma were included and compared to 19 age-matched controls. RESULTS: We observed a statistically significant increase in the absolute mean hippocampal volume (p = 0.017), as well as in the ipsilateral (compared to the lesion, p = 0.027) and the contralateral hippocampal volumes (p = 0.014) in the group of patients. When the data were normalized per total intracranial volume, we confirmed a statistically significant increase only in the contralateral hippocampal volume (p = 0.042). CONCLUSIONS: To the best of our knowledge, this is the first study to explore hippocampal volumetric changes in a cohort of adult patients affected by IDH1 wild-type glioblastoma, according to the latest WHO classification. We demonstrated an adaptive volumetric response of the hippocampus, which was more pronounced on the side contralateral to the lesion, suggesting substantial integrity and resilience of the medial temporal structures before the initiation of multimodal treatments.

Epileptiform patterns predicting unfavorable outcome in postanoxic patients: A matter of time?

OBJECTIVE: Historically, epileptiform malignant EEG patterns (EMPs) have been considered to anticipate an unfavorable outcome, but an increasing amount of evidence suggests that they are not always or invariably associated with poor prognosis. We evaluated the prognostic significance of an EMP onset in two different timeframes in comatose patients after cardiac arrest (CA): early-EMPs and late-EMPs, respectively. METHODS: We included all comatose post-CA survivors admitted to our intensive care unit (ICU) between 2016 and 2018 who underwent at least two 30-minute EEGs, collected at T0 (12-36 h after CA) and T1 (36-72 h after CA). All EEGs recordings were re-analyzed following the 2021 ACNS terminology by two senior EEG specialists, blinded to outcome. Malignant EEGs with abundant sporadic spikes/sharp waves, rhythmic and periodic patterns, or electrographic seizure/status epilepticus, were included in the EMP definition. The primary outcome was the cerebral performance category (CPC) score at 6 months, dichotomized as good (CPC 1-2) or poor (CPC 3-5) outcome. RESULTS: A total of 58 patients and 116 EEG recording were included in the study. Poor outcome was seen in 28 (48%) patients. In contrast to late-EMPs, early-EMPs were associated with a poor outcome (p = 0.037), persisting after multiple regression analysis. Moreover, a multivariate binomial model coupling the timing of EMP onset with other EEG predictors such as T1 reactivity and T1 normal voltage background can predict outcome in the presence of an otherwise non-specific malignant EEG pattern with quite high specificity (82%) and moderate sensitivity (77%). CONCLUSIONS: The prognostic significance of EMPs seems strongly time-dependent and only their early-onset may be associated with an unfavorable outcome. The time of onset of EMP combined with other EEG features could aid in defining prognosis in patients with intermediate EEG patterns.

Vessel distance mapping: A novel methodology for assessing vascular-induced cognitive resilience.

The association between cerebral blood supply and cognition has been widely discussed in the recent literature. One focus of this discussion has been the anatomical variability of the circle of Willis, with morphological differences being present in more than half of the general population. While previous studies have attempted to classify these differences and explore their contribution to hippocampal blood supply and cognition, results have been controversial. To disentangle these previously inconsistent findings, we introduce Vessel Distance Mapping (VDM) as a novel methodology for evaluating blood supply, which allows for obtaining vessel pattern metrics with respect to the surrounding structures, extending the previously established binary classification into a continuous spectrum. To accomplish this, we manually segmented hippocampal vessels obtained from high-resolution 7T time-of-flight MR angiographic imaging in older adults with and without cerebral small vessel disease, generating vessel distance maps by computing the distances of each voxel to its nearest vessel. Greater values of VDM-metrics, which reflected higher vessel distances, were associated with poorer cognitive outcomes in subjects affected by vascular pathology, while this relation was not observed in healthy controls. Therefore, a mixed contribution of vessel pattern and vessel density is proposed to confer cognitive resilience, consistent with previous research findings. In conclusion, VDM provides a novel platform, based on a statistically robust and quantitative method of vascular mapping, for addressing a variety of clinical research questions.

CT perfusion extended window ischemic core estimation: Bayesian algorithm versus oscillation index singular value decomposition.

BACKGROUND AND PURPOSE: Ischemic core estimation by CT perfusion (CTp) is a diagnostic challenge, mainly because of the intrinsic noise associated with perfusion data. However, an accurate and reliable quantification of the ischemic core is critical in the selection of patients for reperfusion therapies. Our study aimed at assessing the diagnostic accuracy of two different CTp postprocessing algorithms, that is, the Bayesian Method and the oscillation index singular value decomposition (oSVD). METHODS: All the consecutive stroke patients studied in the extended time window (>4.5 hours from stroke onset) by CTp and diffusion-weighted imaging (DWI), between October 2019 and December 2021, were enrolled. The agreement between both algorithms and DWI was assessed by the Bland-Altman plot, Wilcoxon signed-rank test, Spearman's rank correlation coefficient, and the intraclass correlation coefficient (ICC). RESULTS: Twenty-four patients were enrolled (average age: 72 ± 15 years). The average National Institutes of Health Stroke Scale was 14.42 ± 6.75, the median Alberta Stroke Program Early CT score was 8.50 (interquartile range [IQR] = 7.75-9), and median time from stroke onset to neuroimaging was 7.5 hours (IQR = 6.5-8). There was an excellent correlation between DWI and oSVD (ρ = .87, p-value < .001) and DWI and Bayesian algorithm (ρ = .94, p-value < .001). There was a stronger ICC between DWI and Bayesian algorithm (.97, 95% confidence interval [CI]: .92-.99, p-value < .001) than between DWI and oSVD (.59, 95% CI: .26-.8, p-value < .001). DISCUSSION: The agreement between Bayesian algorithm and DWI was greater than between oSVD and DWI in the extended window. The more accurate estimation of the ischemic core offered by the Bayesian algorithm may well play a critical role in the accurate selection of patients for reperfusion therapies.

Anti-Gad 65 encephalitis with rapidly progressive temporal atrophy reveals the involvement of the temporal lobe in the neuroanatomical basis of palilalia.

Palilalia is an acquired speech disorder characterized by the reiteration of words or sentences, historically divided in two main subtypes: "palilalie heterolalique" and "palilalie homolalique". In the former, the reiteration is characterized by rate increase and volume decrease, while in the latter these features remain unaltered. While the "heterolalique" subtype has been mainly observed in the context of basal ganglia diseases, the neuroanatomical basis of the "homolalique" subtype has never been completely clarified. Here we report the case of an 81 years-old woman who developed an extremely repetitive and perseverative language with "homolalique" subtype features and a rapidly progressive course with severe bitemporal atrophy, as a consequence of anti-glutamic acid decarboxylase 65 (GAD 65) antibodies encephalitis. To the best of our knowledge, this is the first report of palilalia in the context of anti-GAD 65 encephalitis. Through the support of voxel-based morphometry and hippocampal subfields analysis, this case study provides a fascinating way of understanding the networks responsible for palilalia, shedding some light on the critical role of temporal areas in the onset of this rare language disorder.

Heart rate variability and cognitive performance in adults with cardiovascular risk.

Background: Heart rate variability (HRV), a measure of autonomic function, has been associated with both cardiovascular disease and cognitive dysfunction. In turn, cardiovascular risk has been linked to an increased risk of dementia onset. However, whether autonomic dysfunction may represent an early marker of cognitive decline in individuals with high cardiovascular risk is still an open issue. Methods: We performed a complete 24-hour HRV analysis in 50 middle-aged and elderly subjects with cardiovascular risk as assessed with the European Society of Cardiology Systematic Coronary Risk Evaluation (ESC SCORE). Cognitive performance was evaluated by Montreal Cognitive Assessment (MoCA), Free and Cued Selective Reminding Test (FCSRT) and Stroop Color and Word Test. Stepwise regression was used to identify significant associations between 24-hour ambulatory ECGs parameters and cognitive performances. Results: There were 30 women and 20 men with mean age of 64.9 years (range 51-77) and the mean ESC SCORE was 6%. Four subjects were diagnosed with mild cognitive impairment. Associations were found between measures of HRV and measures of cognition. Ultra-low frequency (ULF) band power of HRV significantly correlated with MoCA (r = 0.424, p = 0.003), also after adjustment for demographics and education. A significant association was also found between the ESC SCORE and ULF band power (r = -0.470, p = 0.0009). Conclusions: Ultra-low frequency band power of HRV is associated with cognitive performance of middle-aged and elderly subjects with cardiovascular risk. This finding may indicate that autonomic nervous system dysregulation plays a role in developing cardiovascular risk and cognitive decline.

Dementia-related genetic variants in an Italian population of early-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) is the most common form of early-onset dementia. Although three major genes have been identified as causative, the genetic contribution to the disease remains unsolved in many patients. Recent studies have identified pathogenic variants in genes representing a risk factor for developing Alzheimer's disease (AD) and in causative genes for other degenerative dementias as responsible for EOAD. To study them further, we investigated a panel of candidate genes in 102 Italian EOAD patients, 45.10% of whom had a positive family history and 21.74% with a strong family history of dementia. We found that 10.78% of patients carried pathogenic or likely pathogenic variants, including a novel variant, in PSEN1, PSEN2, or APP, and 7.84% showed homozygosity for the ε4 APOE allele. Additionally, 7.84% of patients had a moderate risk allele in PSEN1, PSEN2, or TREM2 genes. Besides, we observed that 12.75% of our patients carried only a variant in genes associated with other neurodegenerative diseases. The combination of these variants contributes to explain 46% of cases with a definite familiarity and 32% of sporadic forms. Our results confirm the importance of extensive genetic screening in EOAD for clinical purposes, to select patients for future treatments and to contribute to the definition of overlapping pathogenic mechanisms between AD and other forms of dementia.

Sleep and brain evolution across the human lifespan: A mutual embrace.

Sleep can be considered a window to ascertain brain wellness: it dynamically changes with brain maturation and can even indicate the occurrence of concealed pathological processes. Starting from prenatal life, brain and sleep undergo an impressive developmental journey that accompanies human life throughout all its steps. A complex mutual influence rules this fascinating course and cannot be ignored while analysing its evolution. Basic knowledge on the significance and evolution of brain and sleep ontogenesis can improve the clinical understanding of patient's wellbeing in a more holistic perspective. In this review we summarized the main notions on the intermingled relationship between sleep and brain evolutionary processes across human lifespan, with a focus on sleep microstructure dynamics.

Hippocampal vascularization patterns exert local and distant effects on brain structure but not vascular pathology in old age.

The hippocampus within the medial temporal lobe is highly vulnerable to age-related pathology such as vascular disease. We examined hippocampal vascularization patterns by harnessing the ultra-high resolution of 7 Tesla magnetic resonance angiography. Dual-supply hemispheres with a contribution of the anterior choroidal artery to hippocampal blood supply were distinguished from single-supply ones with a sole dependence on the posterior cerebral artery. A recent study indicated that a dual vascular supply is related to preserved cognition and structural hippocampal integrity in old age and vascular disease. Here, we examined the regional specificity of these structural benefits at the level of medial temporal lobe sub-regions and hemispheres. In a cross-sectional study with an older cohort of 17 patients with cerebral small vessel disease (70.7 ± 9.0 years, 35.5% female) and 27 controls (71.1 ± 8.2 years, 44.4% female), we demonstrate that differences in grey matter volumes related to the hippocampal vascularization pattern were specifically observed in the anterior hippocampus and entorhinal cortex. These regions were especially bigger in dual-supply hemispheres, but also seemed to benefit from a contralateral dual supply. We further show that total grey matter volumes were greater in people with at least one dual-supply hemisphere, indicating that the hippocampal vascularization pattern has more far-reaching structural implications beyond the medial temporal lobe. A mediation analysis identified total grey matter as a mediator of differences in global cognition. However, our analyses on multiple neuroimaging markers for cerebral small vessel disease did not reveal any evidence that an augmented hippocampal vascularization conveys resistance nor resilience against vascular pathology. We propose that an augmented hippocampal vascularization might contribute to maintaining structural integrity in the brain and preserving cognition despite age-related degeneration. As such, the binary hippocampal vascularization pattern could have major implications for brain structure and function in ageing and dementia independent of vascular pathology, while presenting a simple framework with potential applicability to the clinical setting.