Incidence and Prevalence of Dementia: A 2015-2020 Population-Based Study in the Campania Region of Italy.

OBJECTIVE: The aims of this study were to provide population-based estimates of prevalence and incidence of any dementia and Alzheimer's dementia (AD) in the Campania region (South Italy) and to validate towards a clinical registry. METHODS: This was a population-based study, using routinely collected healthcare data of individuals living in the Campania region (South Italy) from 2015 to 2020. We included individuals aged ≥65 years alive at the prevalence day (January 1, 2021) who had at least one administrative record for dementia and/or AD from 2015 to 2020. Age-and sex-standardised prevalence rates were calculated using direct standardisation method (European population in 2020 as the reference population). To estimate the incidence, we tested three possible algorithms, which differed for the duration of the time interval between study baseline (January 1, 2015) and index date (first record for dementia and/or AD in administrative databases). We employed a clinical database for the validation of our algorithms towards neuropsychological test results. RESULTS: Among individuals aged over 65 years, 80,392 had dementia, of which 35,748 had AD. The age- and sex-standardised prevalence rates per 1,000 individuals for any dementia and AD were 77.64 (95% confidence interval [CI] = 77.57; 77.68) and 34.05 (95% CI = 34.01; 34.09), respectively. There were 82.10 incident cases of any dementia per 100,000 per year (0.79 sensitivity and 0.62 specificity) and 59.89 incident cases of AD per 100,000 per year (0.80 sensitivity and 0.59 specificity). The capture-recapture method showed a very low number of undetected cases (1.7% for any dementia and 3.0% for AD). Our algorithms showed acceptable performance with the area under the curve ranging from 0.59 to 0.72 and a double likelihood ratio of correctly identifying individuals above and below mini-mental status examination (MMSE) standard cut-offs (24 and 26). CONCLUSIONS: Prevalence and incidence of any dementia and AD in the Campania region (South Italy) from 2015 to 2020 are in line with previous estimates from other countries. Our algorithm, integrating administrative and clinical data, holds potential for assessing dementia's epidemiological burden, identifying risk factors, planning healthcare access, and developing prevention strategies.

Low serum 25­hydroxy-vitamin D levels are associated with cognitive impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment frequently affects people with multiple sclerosis (MS). Low vitamin D has been associated with cognitive dysfunction in different neurodegenerative diseases, and, in MS, with motor disability and disease activity. We aim to investigate associations between vitamin D and cognitive status in MS. METHODS: In this cross-sectional study, we included 181 MS patients, recruited consecutively at the MS Unit of the Policlinico Federico II University Hospital of Naples, Italy, between January and April 2022, with serum 25­hydroxy (25-OH) vitamin D measurements using Chemiluminescence-ImmunoAssay, and cognitive assessment using the Brief International Cognitive Assessment for MS (BICAMS), which includes Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II) and Brief Visuospatial Memory Test-Revised (BVMT-R). We collected demographics (age, sex, education), and clinical variables (disease duration, disease subtype, expanded disability status scale (EDSS), disease modifying treatment, relapses in previous 12 months, vitamin D supplementation, comorbidities). For a subset of patients (n = 41, 23.2% of the total sample), we collected Beck Depression Inventory-II, Beck Anxiety Inventory, and Modified Fatigue Impact Scale. RESULTS: At univariable linear regression models, serum 25-OH-vitamin D levels were 0.9 ng/mL higher for each unit increase of SDMT adjusted scores (Coeff=0.93; 95%CI=0.81, 1.04; p<0.01), 0.7 ng/mL higher for each unit increase of CVLT-II adjusted scores (Coeff=0.68; 95%CI=0.53, 0.83; p<0. 01), 0.6 ng/mL higher for each unit increase of BVMT-R adjusted scores (Coeff=0.58; 95%CI=0.43, 0.73; p<0.01), -9.63 ng/mL lower for each impaired BICAMS test (Coeff=-9.63; 95%CI=-11.48, -7.79; p<0.01), and -2.2 ng/mL lower for each unit increase of EDSS (Coeff=-2.16; 95%CI=-3.57, -0.75; p<0.01). At multivariable linear regression models, we confirmed associations between 25-OH-vitamin D and EDSS (Coeff=-2.09; 95%CI=-4.45, -0.43; p<0.01), SDMT (Coeff=0.75; 95%CI=0.60, 0.90; p<0.01), and CVLT-II (Coeff=0.14; 95%CI=0.01, 0.28; p = 0. 04). Results remained unchanged when including depression, anxiety and fatigue scores. CONCLUSIONS: Lower serum 25-OH-vitamin D was associated with worse cognitive function in MS. Future studies should consider longitudinal variations in cognitive function in relation to vitamin D supplementation.

Determinants of early working impairments in multiple sclerosis.

Introduction: Unemployment can directly affect social status and identity. Assessing and adjusting determinants of early working impairments in a chronic disease can thus reduce its long-term burden. Hereby, we aim to evaluate differences in occupational history and early working impairments between people with multiple sclerosis (MS) and healthy workers. Methods: This is a cross-sectional study comparing 71 workers with MS [age 41.7 ± 9.4 years; females 59.1%; EDSS 2.0 (1.0-6.0)] and 71 controls (age 42.6 ± 11.9 years; females 33.8%). All participants filled in Work Ability Index (WAI), Work Productivity and Activity Impairment (WPAI), European Questionnaire for Quality of Life (EuroQoL), Beck Depression Inventory II (BDI-II), and Pittsburgh Sleep Quality Index (PSQI). In MS, we further collected expanded disability status scale (EDSS), MS Questionnaire for Job difficulties (MSQ-Job), Fatigue severity scale (FSS), and the Brief International Cognitive Assessment for MS (BICAMS). Results: Workers with MS were more working disabled (p < 0.01), less exposed to workplace risks (p < 0.01), and more limited in fitness to work (p = 0.01), compared with controls. On linear regression models adjusted by age, sex, education, and type of contract, people with MS had worse WAI (Coeff=-5.47; 95% CI = -7.41, -3.53; p < 0.01), EuroQoL (Coeff = -4.24; 95% CI = -17.85, -6.50; p < 0.01), BDI-II (Coeff = 3.99; 95% CI = 2.37, 7.01; p < 0.01), and PSQI (Coeff = 4.74; 95% CI = 3.13, 7.61; p < 0.01), compared with controls, but no differences in WPAI (p = 0.60). EuroQoL, BDI-II, and PSQI were equally associated with both WAI and WPAI in MS and controls (all p< 0.01). In MS, worse MSQJob was associated with higher EDSS (Coeff = 5.22; 95% CI = 2.24, 7.95; p < 0.01), progressive disease (Coeff = 14.62; 95% CI = 5.56, 23.69; p < 0.01), EuroQoL (Coeff = 4.63; 95% CI = 2.92, 6.35; p < 0.01), FSS (Coeff = 0.55; 95% CI = 0.38, 0.72; p < 0.01), and cognitive impairment (Coeff = 4.42; 95% CI = 0.67, 8.22; p = 0.02). Discussion: Early factors associated with working difficulties in MS include disability, fatigue, depression, and cognitive dysfunction. Early identification of clinical features potentially causing working difficulties should be considered to enhance job retention, along with targeted prevention and protection measures.

Persistence with Botulinum Toxin Treatment for Spasticity Symptoms in Multiple Sclerosis.

Botulinum toxin (BT) is an effective treatment for spasticity symptoms in multiple sclerosis (MS). Despite its wide use in clinical practices, only few studies have explored long-term persistence. We aim to evaluate the rate of discontinuation of BT treatment and the correlation with MS, spasticity, and injection variables. This retrospective study on 3-year prospectively collected data included 122 MS patients receiving BT injections for spasticity. We collected MS clinical variables (disease durations, Expanded Disability Status Scales [EDSSs], disease-modifying treatments [DMT], and Symbol Digit Modalities Tests [SDMTs]), modified Ashworth scales [MASs], concomitant treatments, and injection variables (formulation, dose, number of injections, and intervals between injections). A total of 14 out of the 122 patients discontinued BT after a mean time of 3.0 ± 1.5 years. In the Cox regression model including the MS clinical variables, the probability of BT discontinuations increased in patients with DMT changes during follow-ups (HR = 6.34; 95%Cl = 2.47, 18.08; p < 0.01) and with impaired SDMTs (HR = 1.20; 95%Cl = 1.04, 1.96; p < 0.01). In the model including the spasticity variables, there were no associations between BT discontinuation and MAS or other spasticity treatments. In the model including the injection variables, the probability of discontinuation decreased by 80% for each cumulative injection (HR = 0.16; 95%Cl = 0.05, 0.45; p < 0.01), but increased by 1% for each additional day over the 3-month interval between injections (HR = 1.27; 95%Cl = 1.07, 1.83; p < 0.01). BT discontinuation was associated with concomitant MS-related issues (e.g., treatment failure and DMT change) and the presence of cognitive impairment, which should be accounted for when planning injections. The interval between injections should be kept as short as possible from regulatory and clinical perspectives to maximize the response across all of the spasticity symptoms and to reduce discontinuation in the long term.

Cognitive trajectories in multiple sclerosis: a long-term follow-up study.

BACKGROUND: Cognitive impairment occurs in multiple sclerosis (MS) and undergoes a progressive worsening over disease course. However, clinicians still struggle to predict the course of cognitive function. To evaluate baseline clinical and imaging predictors of cognitive abilities worsening over time, we performed a latent trajectory analysis for cognitive performances in MS patients, up to 15 years from disease onset. METHODS: We collected age, sex, education, dominant and non-dominant 9-hole peg test (9HP) and timed 25-foot walk (T25-FW) as well as MRI measures (grey matter volume and lesion load) within 6 months from disease diagnosis for relapsing-remitting MS (RR-MS) patients. At diagnosis and over the follow-up, we also assessed cognitive status through the symbol digit modalities test (SDMT). Cognitive impairment was defined by applying age-, gender- and education-adjusted normative values. Group-based trajectory analysis was performed to determine trajectories, and the predictive value of clinical and imaging variables at baseline was assessed through multinomial logistic regression. RESULTS: We included 148 RR-MS (98 females and 50 males). Over 11 ± 4 year follow-up, 51.4% remained cognitively stable whereas 48.6% cognitively worsened. Cognitively worsening patients had a higher T25FW time (p = 0.004) and a reduced hippocampal volume at baseline (p = 0.04). CONCLUSION: Physical disability as well as hippocampal atrophy might depict patients at risk of cognitive worsening over the disease course. Therefore, using such predictors, clinicians may select patients to carefully evaluate for cognitive impairment as to eventually introduce cognitive rehabilitation treatments.

Interplay Between Cognitive and Bowel/Bladder Function in Multiple Sclerosis.

PURPOSE: The aim of this study was to evaluate the prevalence of bowel/bladder dysfunction in multiple sclerosis (MS) and its associations with cognitive impairment. METHODS: We prospectively enrolled 150 MS patients. Patients were administered the Symbol Digit Modality Test (SDMT), the Neurogenic Bowel Dysfunction Score (NBDS), and the Actionable Bladder Symptom Screening Tool (ABSST). The associations between bowel/bladder dysfunction and cognitive function were assessed through hierarchical regression models using the SDMT and clinicodemographic features as independent variables and NBDS and ABSST scores as dependent variables. RESULTS: The prevalence of bowel/bladder deficits was 44.7%, with 26 patients (17.3%) suffering from bowel deficits and 60 patients (40%) from bladder deficits. The total NBDS and ABSST scores were correlated with the SDMT (ß=-0.10, P<0.001 and ß=-0.03, P=0.04, respectively) after correction for demographic features and physical disability. CONCLUSION: Bowel/bladder disorders are common in MS and are associated with both physical and cognitive disability burdens. As SDMT is embedded into routine clinical assessments, a lower score may warrant investigating bowel/bladder dysfunction due to the strong interplay of these factors.

A Retrospective Exploratory Analysis on Cardiovascular Risk and Cognitive Dysfunction in Multiple Sclerosis.

BACKGROUND: Cardiovascular comorbidities have been associated with cognitive decline in the general population. OBJECTIVES: To evaluate the associations between cardiovascular risk and neuropsychological performances in MS. METHODS: This is a retrospective study, including 69 MS patients. For all patients, we calculated the Framingham risk score, which provides the 10-year probability of developing macrovascular disease, using age, sex, diabetes, smoking, systolic blood pressure, and cholesterol levels as input variables. Cognitive function was examined with the Brief International Cognitive Assessment for MS (BICAMS), including the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-II (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). RESULTS: Each point increase of the Framingham risk score corresponded to 0.21 lower CVLT-II score. Looking at Framingham risk score components, male sex and higher total cholesterol levels corresponded to lower CVLT scores (Coeff = -8.54; 95%CI = -15.51, -1.57; and Coeff = -0.11; 95%CI = -0.20, -0.02, respectively). No associations were found between cardiovascular risk and SDMT or BVMT-R. CONCLUSIONS: In our exploratory analyses, cardiovascular risk was associated with verbal learning dysfunction in MS. Lifestyle and pharmacological interventions on cardiovascular risk factors should be considered carefully in the management of MS, given the possible effects on cognitive function.

Predictors of Nabiximols (Sativex®) discontinuation over long-term follow-up: a real-life study.

Nabiximols is an effective treatment for spasticity in MS. However, treatment discontinuation over-time might occur and predictors of sustained treatment persistence over long-term follow-up in real-world settings are highly needed. We aim at evaluating baseline predictors of treatment persistence on Nabiximols. This is a retrospective real-world study including MS patients treated with Nabiximols. At baseline (Nabiximols prescription), we evaluated disability using the EDSS, and cognitive function using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Nabiximols discontinuation was evaluated after 4 weeks of treatment ("titration phase''), and over the follow-up ("treatment phase"). We included 396 MS patients (228 females and 168 males). After 4 weeks (titration phase), 266 MS patients (67.2%) were considered persistent on treatment, while 130 patients dropped out. After 19 ± 21 months (treatment phase), 136 out of 266 MS patients (51.1%) were still on treatment, whereas 130 patients dropped at follow-up. Higher EDSS and cognitive impairment predicted treatment discontinuation at follow-up (p = 0.04 and p = 0.005, respectively). In conclusion, higher physical and cognitive disability predicted Nabiximols treatment discontinuation over 2 years in MS patients suffering from spasticity. Nabiximols should be started earlier to decrease the likelihood of treatment discontinuation over time.

Correction to: Normative values of the Rao's Brief Repeatable Battery in an Italian young adolescent population: the influence of age, gender, and education.

The published version of this article unfortunately contained a mistake in Table 2.

Normative values of the Rao's Brief Repeatable Battery in an Italian young adolescent population: the influence of age, gender, and education.

AIM: The Brief Repeatable Battery of Neuropsychological Tests (BRB) is frequently used to estimate cognitive function in adults with multiple sclerosis (MS), while it has been included in few studies on young MS, also because of the absence of normative values. We aim to evaluate the impact of age, gender, and education on BRB scores in a young adolescent population. METHODS: We administered the BRB to 76, 14-to-17-year-old, healthy subjects. Linear regression models were used to assess the impact of age, gender, and education on sub-test scores. When statistically significant (p < 0.05), we used the regression coefficient to correct the raw scores. RESULTS: Younger age was associated with better performance on SPART (ß = - 2.54; p < 0.05) and SPART-D (ß = - 1.06; p < 0.05). Male gender was associated with better performance on SPART (ß = 3.40; p < 0.05), SPART-D (ß = 1.41; p < 0.05), PASAT-3 (ß = 5.58; p < 0.05), and PASAT-2 (ß = 5.07; p < 0.05). Educational attainments were associated with better performance on SPART (ß = 3.23; p < 0.05) and SPART-D (ß = 1.28; p < 0.05). Cut-off points were suggested at the 5th lowest percentile. INTERPRETATION: Age, gender, and education must be accounted for when applying the BRB to young population. Present results can prove useful for future clinical and research applications in adolescent MS patients.

Cognitive dysfunctions and psychological symptoms in migraine without aura: a cross-sectional study.

BACKGROUND: The occurrence of cognitive dysfunctions and psychological symptoms, as well as their mutual relationships, in migraine patients are still debated. The aim of the study was to characterize the cognitive profile and psychological symptoms (i.e. depression, anxiety and apathy) in drug-naïve migraine without aura (MwoA) patients. METHODS: Seventy-two consecutive MwoA patients, referred to the Italian University Headache Clinic and 72 healthy subjects (HCs) were enrolled. Patients, during an attack-free period, and HCs completed Montreal Cognitive Assessment (MoCA), Beck Depression Inventory-II (BDI-II), Self-version of Apathy Evaluation Scale (AES-S) and State and Trait Anxiety Inventory (STAI-Y-1 and 2). Clinical parameters of disease severity (i.e. disease duration, migraine attacks per month, mean pain intensity during migraine attacks, migraine disability and impact on daily life) were recorded. RESULTS: Although performance of MwoA patients on MoCA was above Italian cut-off threshold (<15.5) suggesting presence of cognitive impairment, MwoA patients achieved significantly lower scores than HCs on total MoCA scale (22.3 ± 2.7 versus 25.4 ± 2.3) and on its attention (4.9 ± 1.1 versus 5.6 ± 0.7), memory (1.8 ± 1.4 versus 3.1 ± 1.3), visuospatial (3.2 ± 0.9 versus 3.6 ± 0.6) and executive subscales (2.6 ± 1.1 versus 3.1 ± 0.8). In addition, we observed significant correlations between MoCA executive domain subscore and the attack-related disability score (MIDAS). As for behavioral profile, the percentage of depressive symptoms (4.2 %), high state and trait anxiety (13.9 and 9.7 %, respectively), and apathy (11.1 %) in MwoA patients were similar to that of HCs. No significant associations of behavioural symptoms with cognitive performance and clinical parameters were found. CONCLUSIONS: Drug-naïve MwoA patients are characterized by subtle cognitive dysfunctions and low percentage of behavioural symptoms. The results support the importance of searching for subclinical cognitive disturbances in patients with MwoA, who deserve to be followed-up to verify whether they develop clinically relevant disorders over time.

Anxiety in early Parkinson's disease: Validation of the Italian observer-rated version of the Parkinson Anxiety Scale (OR-PAS).

INTRODUCTION: Anxiety disorders are common in Parkinson's Disease (PD) and their identification is relevant even at early stages. The Parkinson Anxiety Scale (PAS) evaluates anxiety in PD; it was used only in the original validation study in PD patients mainly at 2-3 stages of Hoehn & Yahr system (H&Y). The study aimed to investigate psychometric properties of observer-rated version of the PAS (OR-PAS), prevalence rate of anxiety and its features, compared with diagnostic criteria in early PD patients. METHODS: A sample of 101 PD patients with H&Y:1-2 underwent the OR-PAS. To assess convergent and divergent validity, PD patients underwent Beck Anxiety Inventory, and scales assessing depression, apathy, anhedonia and cognition. To diagnose anxiety disorders, Mini International Neuropsychiatric Inventory was used as gold standard. A "receiver operating characteristics" curve was obtained; positive and negative predictive values were calculated for different cut-off points of the OR-PAS and its subscales. RESULTS: There was no missing data, no floor and ceiling effects; mean score was 12.2±10.1; Cronbach's alpha was 0.899. The OR-PAS showed good convergent and divergent validity. Maximum discrimination was obtained with a cut-off score of 8.5. The anxiety occurred in 59 patients (58.4%). CONCLUSION: The OR-PAS is a reliable and valid screening instrument for assessing anxiety in patients at early PD. Anxiety was found in 58.4% of PD patients, demonstrating that anxiety occurs even at early stages.

Neuropsychological correlates of Pisa syndrome in patients with Parkinson's disease.

BACKGROUND: A complex relationship exists between postural control and cognition in the elderly. Namely, neural mechanisms that are required for the regulation of posture have been variably associated with cognitive dysfunctions. Parkinson's disease (PD) is the second most common neurodegenerative disease among the elderly, and it has been associated with both cognitive and postural abnormalities such as Pisa syndrome (PS). Although its onset has been considered to be multifactorial, the pathophysiological mechanisms underpinning PS are still not fully explained. Until now, no study investigated the possible contribution of cognitive dysfunction to occurrence of PS in PD. PATIENTS AND METHODS: Twenty PD patients with PS and 20 PD patients without PS were enrolled. All patients with PD underwent neuropsychological battery to assess behavioural disturbances, memory, attention, frontal/executive and visuospatial functions. RESULTS: The two groups did not differ on demographic features, age at PD onset and disease duration, whereas they significantly differed on UPDRS-Part III, and levodopa-equivalent daily dose (LEDD). MANCOVA with above-mentioned clinical variable as covariates revealed significant differences on tasks tapping verbal long-term memory, and attentional and visuoperceptual abilities between groups. The binary logistic regression revealed that higher LEDD and lower performance on visuospatial task (Benton Judgment of Lines Orientation test) significantly predicted occurrence of PS. CONCLUSION: Our results revealed a significant association of PS with altered attention and visuoperceptual functions in PD, suggesting that the occurrence of PS may be associated with alteration of both frontal-striatal systems and posterior cortical areas.

Normative data for the Montreal Cognitive Assessment in an Italian population sample.

The Montreal Cognitive Assessment (MoCA) is a rapid screening battery, also including subtests to assess frontal functions such as set-shifting, abstraction and cognitive flexibility. MoCA seems to be useful to identify non-amnestic mild cognitive impairment (MCI) and subcortical dementia; it has high sensitivity and specificity in distinguishing MCI from mild Alzheimer's Disease. Previous studies revealed that certain items of MoCA may be culturally biased and highlighted the need for population-based norms for the MoCA. The aim of present study was to collect normative values in a sample of Italian healthy subjects. Four hundred and fifteen Italian healthy subjects (252 women and 163 men) of different ages (age range 21-95 years) and educational level (from primary to university) underwent MoCA and Mini Mental State Examination (MMSE). Multiple linear regression analysis revealed that age and education significantly influenced performance on MoCA. No significant effect of gender was found. From the derived linear equation, a correction grid for MoCA raw scores was built. Inferential cut-off score, estimated using a non-parametric technique, is 15.5 and equivalent scores were computed. Correlation analysis showed a significant but weak correlation between MoCA adjusted scores with MMSE adjusted scores (r = 0.43, p < 0.001). The present study provided normative data for the MoCA in an Italian population useful for both clinical and research purposes.