Photophobia and migraine outcome during treatment with galcanezumab

BackgroundCalcitonin gene-related peptide (CGRP) plays a pivotal role in migraine physiology, not only regarding migraine pain but also associated symptoms such as photophobia. The aim of the present study was to assess monoclonal antibodies targeting CGRP efficacy not only in terms of headache and migraine frequency and disability but also in reducing ictal photophobia.Material and methodsThis is a retrospective observational study, conducted at the Headache Center–ASST Spedali Civili Brescia. All patients in monthly treatment with galcanezumab with at least a 6-month follow-up in September 2022 with reported severe photophobia during migraine attacks were included. Data regarding headache frequency, analgesics consumption, and migraine disability were collected quarterly. Moreover, patients were asked the following information regarding photophobia: (1) whether they noticed an improvement in photophobia during migraine attacks since galcanezumab introduction; (2) the degree of photophobia improvement (low, moderate, and high); and (3) timing photophobia improvement.ResultsForty-seven patients were enrolled in the present study as they met the inclusion criteria. Seventeen patients had a diagnosis of high-frequency episodic migraine and 30 of chronic migraine. From baseline to T3 and T6, a significant improvement in terms of headache days (19.2 ± 7.6 vs. 8.6 ± 6.8 vs. 7.7 ± 5.7; p < 0.0001), migraine days (10.4 ± 6.7 vs. 2.9 ± 4.3 vs. 3.6 ± 2.8; p < 0.0001), analgesics consumption (25.1 ± 28.2 vs. 7.6 ± 7.5 vs. 7.6 ± 8.1; p < 0.0001), MIDAS score (82.1 ± 48.4 vs. 21.6 ± 17.6 vs. 18.1 ± 20.5; p < 0.0001), and HIT-6 score (66.2 ± 6.2 vs. 57.2 ± 8.6 vs. 56.6 ± 7.6; p < 0.0001) was found. Thirty-two patients (68.1%) reported a significant improvement in ictal photophobia, with over half of the patients reporting it within the first month of treatment. Photophobia improvement was more frequent in patients with episodic migraine (p = 0.02) and triptans responders (p = 0.03).ConclusionsThe present study confirms previous reports regarding galcanezumab efficacy beyond migraine frequency. In particular, over 60% of patients, in our cohort, documented a significant improvement also in reducing ictal photophobia. This improvement was, in most patients, moderate to high, and within the first 6 months of treatment, regardless of the clinical response on migraine frequency

Differences Between Plasma and Cerebrospinal Fluid p-tau181 and p-tau231 in Early Alzheimer's Disease

Plasma phosphorylated tau species have been recently proposed as peripheral markers of Alzheimer's disease (AD) pathology. In this cross-sectional study including 91 subjects, plasma and cerebrospinal fluid (CSF) p-tau181 and p-tau231 levels were elevated in the early symptomatic stages of AD. Plasma p-tau231 and p-tau181 were strongly related to CSF phosphorylated tau, total tau and amyloid and exhibited a high accuracy-close to CSF p-tau231 and p-tau181-to identify AD already in the early stage of the disease. The findings might support the use as diagnostic and prognostic peripheral AD biomarkers in both research and clinical settings

Non-amnestic mild cognitive impairment and sleep complaints: a bidirectional relationship?

Prior studies documented that several sleep disorders may coexist in patients affected by Mild Cognitive Impairment (MCI) and Alzheimer disease (AD), and have a strong bidirectional relationship with cognitive decline

Potentially Serious Drug-Drug Interactions in Older Patients Hospitalized for Acute Ischemic and Hemorrhagic Stroke

8nononenoneCaratozzolo, Salvatore; Gipponi, Stefano; Marengoni, Alessandra; Pari, Elisa; Scalvini, Andrea; Pasina, Luca; Magoni, Mauro; Padovani, AlessandroCaratozzolo, Salvatore; Gipponi, Stefano; Marengoni, Alessandra; Pari, Elisa; Scalvini, Andrea; Pasina, Luca; Magoni, Mauro; Padovani, Alessandr

Association of APOE genotype with blood-brain barrier permeability in neurodegenerative disorders

Apolipoprotein E (APOE) is recognized for its role in modulating blood-brain barrier (BBB) permeability in vitro, which may have significant implications for the pathogenesis and progression of neurodegenerative disorders. However, evidence in vivo is contrasting. This study explores the impact of APOE genotypes on BBB integrity among 230 participants experiencing cognitive impairment, encompassing cases of Alzheimer's disease (AD) as well as various non-AD neurodegenerative conditions. To assess BBB integrity, we utilized cerebrospinal fluid (CSF)/serum albumin ratios and CSF/serum kappa and lambda free light chains (FLCs) as indirect markers. Our findings show a dose-dependent increase in BBB permeability in individuals carrying the APOE e4 allele, marked by elevated CSF/serum albumin and FLCs ratios, with this trend being especially pronounced in AD patients. These results highlight the association of APOE epsilon 4 with BBB permeability, providing valuable insights into the pathophysiology of neurodegenerative diseases

Diagnostic Accuracy of the Five-Word Test for Mild Cognitive Impairment Due to Alzheimer’s Disease

New diagnostic methods have been developed for the early diagnosis of Alzheimer’s disease (AD) with the primary purpose of intercepting the transition-phase (mild cognitive impairment, MCI) between normal aging and dementia. We aimed to explore whether the five-word test (FWT) and the mini-mental state examination (MMSE) are predictive for the early diagnosis of MCI due to AD (AD-MCI). We computed ROC analyses to evaluate the sensitivity and specificity of MMSE and FWT in predicting abnormal CSF (t-Tau, p-Tau181, Aβ1–42) and amyloid-PET biomarkers. AD-MCI patients showed lower MMSE and FWT scores (all p 42, t-Tau and p-Tau181 values, with higher accuracy for the t-Tau/Aβ1–42 ratio. In conclusion, the FWT, as a single-domain cognitive screening test, seems to be prompt and moderately accurate tool for the identification of an underlying AD neuropathological process in patients with MCI, supporting the importance of associating biomarkers evaluation in the work-up of patients with dementing neurodegenerative disorders

Diagnosis of Mild Cognitive Impairment Due to Alzheimer's Disease with Transcranial Magnetic Stimulation

Considering the increasing evidence that disease-modifying treatments for Alzheimer's disease (AD) must be administered early in the disease course, the development of diagnostic tools capable of accurately identifying AD at early disease stages has become a crucial target. In this view, transcranial magnetic stimulation (TMS) has become an effective tool to discriminate between different forms of neurodegenerative dementia

Sex Differences in the Severity and Progression of Neuropsychiatric Symptoms Across Different Dementia Types

Background and objectives: Dementia presents not only differing neuropsychiatric symptoms (NPS) across Alzheimer disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB) but also subjective cognitive decline (SCD). This study examined sex-based variations in NPS severity and progression across these conditions. Methods: We performed a longitudinal cohort study including 1,068 participants. Hierarchical generalized linear mixed models were used to model NPS as a function of disease severity and biological sex at birth. Results: Female participants with AD exhibited NPS more frequently than male participants. In FTD, female participants had more frequent delusions, hallucinations, and depression/dysphoria, while male participants had higher instances of agitation/aggression, apathy, disinhibition, and irritability/lability. In DLB, male participants showed higher instances of depression, and female participants more frequently experienced anxiety. In SCD, female participants showed higher nighttime behaviors. The trajectory of NPS significantly differed between sexes. Discussion: These findings highlight sex-specific NPS impact in different neurodegenerative conditions