Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: Who gains from it?

Background and purpose: Although two doses of COVID-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease-modifying therapies (DMTs) showed less efficient responses. Methods: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS. Results: Four hundred seventy-three pwMS were analyzed. Compared to untreated patients, there was a 50-fold decrease (95% confidence interval [CI] = 14.3–100.0, p < 0.001) in serum SARS-CoV-2 antibody levels in those on rituximab, a 20-fold decrease (95% CI = 8.3–50.0, p < 0.001) in those on ocrelizumab, and a 2.3-fold decrease (95% CI = 1.2–4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti-CD20 drugs rituximab and ocrelizumab showed a 2.3-fold lower gain (95% CI = 1.4–3.8, p = 0.001), whereas those on fingolimod showed a 1.7-fold higher gain (95% CI = 1.1–2.7, p = 0.012), compared to patients treated with other DMTs. Conclusions: All pwMS increased their serum SARS-CoV-2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (>659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff

Oxidative DNA damage in peripheral leukocytes of mild cognitive impairment and AD patients

Abstract It is well established that oxidative stress plays a key role in the degenerative neuronal death and progression of Alzheimer’s disease (AD), although it is not clear if it is the primary triggering event in the pathogenesis of this disorder. Mild cognitive impairment (MCI) is a clinical condition between normal aging and AD, characterized by a memory deficit without loss of general cognitive and functional abilities. We performed this study by a comet assay analysis to evaluate the level of primary and oxidative DNA damage in two groups of MCI and AD patients, compared to healthy controls. Data showed a significantly higher level of primary DNA damage in leukocytes of AD and also of MCI patients compared to control individuals (average: 2.09±0.79 and 2.47±1.01, respectively for AD and MCI, versus 1.04±0.31 in controls). Moreover, the amount of oxidised DNA bases (both purines and pyrimidines) was significatively higher in the two groups of patients (AD and MCI) compared to controls. Our results give a further indication that oxidative stress, at least at the DNA level, is an earlier event in the pathogenesis of AD

FROM MILD COGNITIVE IMPAIRMENT TO DEMENTIA: A PREVALENCE STUDY IN A DISTRICT OF TUSCANY, ITALY

Objective - A door-to-door two-phase study was designed in order to estimate the prevalence of cognitive deficit amongst the residents of a district in Tuscany (central Italy). Identification of cases with mild cognitive impairment (MCI) was given high priority, because this condition has been suggested as a term for the boundary area between normal aging and dementia. Methods - Of the 1600 subjects who completed the screening phase, 354 scored under the cut-off point of the Mini Mental State Examination and Clinical Dementia Rating and were investigated by means of a standardized diagnostic protocol. Results - The prevalence of MCI and age-related cognitive decline was 4.9 and 9.3%, respectively; low levels of education significantly increased the risk of these conditions. The prevalence of dementia over age 65 was 6.2%, with a significant risk association with age. In our population, Alzheimer's disease was the most frequent type of dementia (prevalence rate 4.2%) and increased risk depending on age, sex and education has been found. Conclusions - Our findings are somewhat similar to previous studies. Further epidemiological and longitudinal studies are warranted to identify which diagnostic category is more predictive for dementia

DAYTIME SLEEPINESS IN MID AND MODERATE ALZHEIMER'S DISEASE AND ITS RELATIONSHIP WITH COGNITIVE IMPAIRMENT

The increased tendency to fall asleep during the daytime together with increased wakefulness during the night has been demonstrated in patients with advanced Alzheimer's disease (AD). The aim of this study was to assess daytime sleep propensity in a cohort of patients with mild/moderate AD and to correlate it with cognitive impairment. Twenty drug-free AD patients meeting the NINCDS-ADRDA criteria for probable AD were evaluated. According to their Clinical Dementia Rating scores, subjects were classified into mild (CDR1; n = 11) and moderate (CDR2; n = 9) dementia patients. A group of 12 healthy subjects was taken as controls. The subjects were evaluated by the multiple sleep latency test (MSLT) after their nocturnal sleep pattern had been assessed by a polysomnographic recording throughout the night before. Both groups of AD patients showed a higher level of daytime sleepiness, which was statistically significant for mean daytime sleep latency (MDSL) (controls versus CDR1 and versus CDR2, CDR1 versus CDR2) and for 10:00 and 12:00 hour naps (controls versus CDR1, controls versus CDR2). In the entire group of AD patients, MDSL was significantly related with MMSE, De Renzi's Token test, verbal fluency, verbal digit span, story recall, Raven's Progressive Matrices, Weigl test and Benton's three-dimensional test. These data indicate that an increased sleep propensity during daytime occurs also in patients with mild/moderate AD detected by objective neurophysiological techniques

Apolipoprotein E genotype and behavioural change in AD

Behavioural dysfunctions are common in patients with Alzheimer disease (AD). Up to 67% of AD patients (pts) present such disturbances, which appear to be associated with endogenous and exogenous factors such as disease stage, environmental factors, and AD genotype. Aim of this study is to assess the relationship between apolipoprotein E (APO E) status and behavioural symptoms in AD pts. Sixty probable AD pts (16 male and 44 female; mean age ± SD: 69 ± 8.1; mean age of onset ± SD: 64.2 ± 7.4; disease duration ± SD: 5 ± 2.5; mean Mini-Mental State Examination score ± SD: 16.6 ± 6.2), according to NINDCS-ADRDA criteria, were assessed with the Neuropsychiatric Inventory (NPI) prior to beginning any anti-dementia treatment and their APO E genotype was determined. Among the population studied 5.7% of pts were E2/E2, 57.1% were E3/E3 and 37.2% was with at least one APOE E4 allele. No correlation was found between APOE genotype and any of the 12 non-cognitive symptoms assessed with NPI, even after controlling for the effect of age onset, sex, duration of illness, and severity of dementia. These findings do not support the hypothesis that neuropsychiatric manifestations of AD are different in patients with the APOE E4 allele