Vortioxetine Treatment for Depression in Patients with Prodromal vs Mild Alzheimer's Disease: A Six-Month, Open-Label, Observational Study.

BACKGROUND: Depressive symptoms are common in Alzheimer disease (AD) from the prodromal stage. The benefits of antidepressants have been investigated in patients with AD dementia with mixed results. OBJECTIVES: This study aimed to compare the efficacy of vortioxetine in prodromal and mild-to-moderate AD patients with depression, and to assess the comparative effect on secondary measures, including behavioral disturbances, cognitive function, and activities of daily living. PARTICIPANTS: All subjects with AD at a single-center dementia center underwent a standard evaluation with mini-mental state examination (MMSE), basic and instrumental activities of daily living (BADL and IADL), geriatric depression scale (GDS), neuropsychiatric inventory (NPI), and clinical evaluation every six months. MEASUREMENTS: The study specifically assessed patients on vortioxetine with available six-month follow-up data. The changes in GDS, NPI, MMSE, BADL/IADL at six months in the entire AD population and mild-to-moderate AD vs prodromal population were analyzed using repeated measure multivariate analyses. Linear regression analyses were implemented to evaluate baseline demographics and clinical characteristics associated with depressive and cognitive improvements at six months. RESULTS: Out of 680 AD patients, 115 were treated with vortioxetine, and 89 with six-month follow-up data were included in the analyses. A significant improvement at follow-up was observed for GDS, NPI total and sub score items (mood, anxiety, apathy, sleep disturbances, eating abnormalities). Both mild-to-moderate and prodromal AD showed a positive GDS response, whereas mild-to-moderate AD showed a better improvement on total NPI and apathy/nighttime behaviors subitems compared to prodromal AD. Higher baseline GDS score was the only variable associated with higher responses in linear regression analyses. MMSE showed a significant improvement at six months in the entire cohort, with a greater effect in prodromal vs mild-to-moderate AD. Cognitive improvement (i.e., MMSE changes) was associated with cognitive status at baseline but independent of the antidepressant/behavioral changes (i.e., GDS/NPI). CONCLUSIONS: Our results suggest that vortioxetine is highly tolerable and clinically effective in both prodromal and mild-to-moderate AD with depression. Patients with mild-to-moderate AD benefited more from a wide range of behavioral disturbances. The study also showed significant improvement in global cognitive measures, especially in prodromal AD subjects. Further studies are needed to investigate the independent beneficial effect of vortioxetine on depression and cognition in AD.

Assessing frailty at the centers for dementia and cognitive decline in Italy: potential implications for improving care of older people living with dementia.

INTRODUCTION: Frailty is strongly associated with the clinical course of cognitive impairment and dementia, thus arguing for the need of its assessment in individuals affected by cognitive deficits. This study aimed to retrospectively evaluate frailty in patients aged 65 years and older referred to two Centers for Cognitive Decline and Dementia (CCDDs). METHODS: A total of 1256 patients consecutively referred for a first visit to two CCDDs in Lombardy (Italy) between January 2021 to July 2022 were included. All patients were evaluated by an expert physician in diagnosis and care of dementia according to a standardized clinical protocol. Frailty was assessed using a 24-items Frailty Index (FI) based on routinely collected health records, excluding cognitive decline or dementia, and categorized as mild, moderate, and severe. RESULTS: Overall, 40% of patients were affected by mild frailty and 25% of the sample has moderate to severe frailty. The prevalence and severity of frailty increased with decreasing Mini Mental State Examination (MMSE) score and advancing age. Frailty was also detected in 60% of patients with mild cognitive impairment. CONCLUSION: Frailty is common in patients referring to CCDDs for cognitive deficits. Its systematic assessment using a FI generated with readily available medical information could help develop appropriate models of assistance and guide personalization of care.

Correlación entre el metabolismo de la glucosa cerebral (18F-FDG) y el flujo sanguíneo cerebral con marcadores de amiloide (18F-florbetapir) en práctica clínica: evidencias preliminares / Correlation between brain glucose metabolism (18F-FDG) and cerebral blood flow with amyloid tracers (18F-florbetapir) in clinical routine: Preliminary evidences

Este estudio comparó el rendimiento de las adquisiciones tempranas de 18F-florbetapir PET/TC con el de 18F-FDG PET/TC. Métodos: Se incluyó a 12 pacientes que se sometieron a PET/TC con 18F-FDG y una PET/TC con 18F-florbetapir en dos tiempos (exploración temprana de 1 a 6 min y exploración tardía de 50 min). La PET/TC fue analizada visualmente por 3médicos de medicina nuclear con diferente experiencia utilizando una escala de 4puntos (0=sin reducción, 1=leve, 2=moderada, 3=reducción severa) para 18F-florbetapir en fase temprana y 18F-FDG imágenes en 10 regiones corticales (frontal bilateral, temporal, parietal, occipital, cingulado/precúneo posterior) y fase tardía de 18F-florbetapir en las mismas regiones corticales utilizando una escala de 3puntos (0=normal, 1=anormal con placas menores, 2=anormal con placas importantes). Usamos SPM12 para el análisis semicuantitativo aplicando un análisis de correlación basado en ROI (considerando precúneo como región objetivo y normalizado para la unión global media), un análisis de covarianza tomando precúneo como objetivo y una comparación de DMN global (red de modo predeterminado). resultados: La concordancia entre lectores fue alta (kappa de Cohen 0,762 para 18F-FDG, 0,775 para 18F-florbetapir en la fase temprana y 0,794 para la fase tardía). Las puntuaciones visuales regionales de la fase temprana y la 18F-FDG se correlacionaron significativamente (ρ=0,867). También el análisis basado en el ROI, el análisis visual cerebral global y la comparación de DMN revelaron resultados concordantes, especialmente en parietal y precúneo (p <0,001). Conclusiones: Las exploraciones de fase temprana de 18F-florbetapir se correlacionan significativamente en imágenes cuantitativas y visuales con las exploraciones de 18F-FDG-PET/TC, lo que sugiere que se podría usar un marcadore de amiloide en lugar de 18F-FDG (AU)

This study compared the performance of 18F-florbetapir PET/CT early acquisitions to 18F-FDG PET/CT. Methods: We included 12 patients who underwent 18F-FDG PET/CT and a dual-time 18F-florbetapir PET/CT (1-6minutes early-scan and 50minutes late-scan). PET/CT were analyzed visually by 3nuclear medicine physicians with different experience using a four-point scale (0=no reduction, 1=slight, 2=moderate, 3=severe reduction) for 18F-florbetapir early-phase and 18F-FDG images in 10 cortical regions (bilateral frontal, temporal, parietal, occipital, posterior cingulate/precuneus), and 18F-florbetapir late-phase in the same cortical regions using a three-point scale (0=normal, 1=abnormal with minor plaques, 2=abnormal with major plaques). We used SPM12 for semiquantitative analysis applying a ROI-based correlation analysis (considering precuneus as target region and normalized for the mean global binding), a covariance-analysis taking precuneus as target and a comparison of global DMN (default mode network). esults: Inter-reader agreement was high (Cohen's kappa 0.762 for 18F-FDG, 0.775 for 18F-florbetapir early-phase and 0.794 for late-phase). Regional visual scores of early-phase and 18F-FDG were significantly correlated (ρ=0.867). Also ROI-based analysis, global brain visual analysis and DMN comparison revealed concordant results, especially at parietal and precuneus(p<0.001). Conclusions: 18F-florbetapir early-phase scans significantly correlate on quantitative and visual images with 18F-FDG-PET/CT scans, suggesting that amyloid tracer could be used instead of 18F-FDG (AU)

Source-Based Morphometry Multivariate Approach to Analyze [123I]FP-CIT SPECT Imaging.

PURPOSE: [123I]FP-CIT (DaTSCAN®) single-photon emission computed tomography (SPECT) imaging is widely used to study neurodegenerative parkinsonism, by measuring presynaptic dopamine transporter (DAT) in striatal regions. Beyond DAT, [123I]FP-CIT may be considered for other monoaminergic systems, in particular the serotonin transporter (SERT). Independent component analysis (ICA) implemented in source-based morphometry (SBM) could represent an alternative method to explore monoaminergic pathways, studying the relationship among voxels and grouping them into "neurotransmission" networks. PROCEDURES: One hundred forty-three subjects [84 with Parkinson's disease (PD) and 59 control individuals (CG)] underwent DATSCAN® imaging. The [123I]FP-CIT binding was evaluated by multivariate SBM approach, as well as by a whole-brain voxel-wise univariate (statistical parametric mapping, SPM) approach. RESULTS: As compared to the univariate whole-brain approach (SPM) (only demonstrating striatal [123I]FP-CIT binding reduction in PD group), SBM identified six sources of non-artefactual origin, including basal ganglia and cortical regions as well as brainstem. Among them, three sources (basal ganglia and cortical regions) presented loading scores (as index of [123I]FP-CIT binding) significantly different between PD and CG. Notably, even if not significantly different between PD and CG, the remaining three non-artefactual sources were characterized by a predominant frontal, brainstem, and occipito-temporal involvement. CONCLUSION: The concept of source blind separation by the application of ICA (as implemented in SBM) represents a feasible approach to be considered in [123I]FP-CIT (DaTSCAN®) SPECT imaging. Taking advantage of this multivariate analysis, specific patterns of variance can be identified (involving either striatal than extrastriatal regions) that could be useful in differentiating neurodegenerative parkinsonisms.

Impulse control disorder in PD: A lateralized monoaminergic frontostriatal disconnection syndrome?

BACKGROUND: Impulse Control Disorder symptoms (ICD) in Parkinson's disease (PD) has been recently associated by magnetic Resonance imaging with impaired cortico-striatal connectivity, especially between left putamen and frontal associative areas. METHODS: 84 patients entered the study (21 PD-ICD+ and 64 PD-ICD-) and underwent DATSCAN imaging. The striatal tracer uptake was evaluated using BRASS software (Hermes, Sweden). The whole-brain analysis was performed with Statistical Parametric Mapping (SPM). RESULTS: PD-ICD+ showed a significant reduction of left putaminal and left inferior frontal gyrus tracer uptake compared to PD-ICD-. Functional covariance analysis using left putamen as the seed point showed that, in contrast to ICD-patients, ICD+ patients had no functional covariance with contralateral basal ganglia and ipsilateral cingulate cortex, as index of an impaired inter- and intra-hemispheric dopamine binding in PD-ICD+. DISCUSSION: the results support and expand the concept of a functional disconnection syndrome linked to ICD symptoms in PD patients through an asymmetric molecular frontostriatal network breakdown with left basal ganglia as central hub.

Subcortical matter in the α-synucleinopathies spectrum: an MRI pilot study.

α-Synucleinopathies, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB), are characterized by α-synuclein accumulation from brainstem structures to the neocortex. PD and DLB are clinically distinguishable, while discrimination between Parkinson Disease Dementia (PDD) and DLB can be subtle and based on the temporal relationship between motor and cognitive symptoms. To explore patterns of subcortical atrophy in PD, PDD and DLB, and assess specific differences between PD and PDD, and between DLB and PDD. 16 PD, 11 PDD and 16 DLB patients were recruited and underwent 1.5 Tesla structural MRI scanning. Segmentation of subcortical structures was performed with a well-validated, fully-automated tool, and volume and shape for each structure were compared between groups. PDD and DLB patients showed global subcortical atrophy compared to PD patients. Greater hippocampal atrophy was the specific trait that distinguished PDD from PD, while greater atrophy of the pallidi discriminated DLB from PDD. Vertex analysis revealed specific shape differences in both structures. Our results suggest that automated, time-sparing, subcortical volumetry may provide diagnostically useful information in α-synucleinopathies. Future studies on larger samples and with iron-sensitive MRI contrasts are needed.

Italian Frontotemporal Dementia Network (FTD Group-SINDEM): sharing clinical and diagnostic procedures in Frontotemporal Dementia in Italy.

In the prospect of improved disease management and future clinical trials in Frontotemporal Dementia, it is desirable to share common diagnostic procedures. To this aim, the Italian FTD Network, under the aegis of the Italian Neurological Society for Dementia, has been established. Currently, 85 Italian Centers involved in dementia care are part of the network. Each Center completed a questionnaire on the local clinical procedures, focused on (1) clinical assessment, (2) use of neuroimaging and genetics; (3) support for patients and caregivers; (4) an opinion about the prevalence of FTD. The analyses of the results documented a comprehensive clinical and instrumental approach to FTD patients and their caregivers in Italy, with about 1,000 newly diagnosed cases per year and 2,500 patients currently followed by the participating Centers. In analogy to other European FTD consortia, future aims will be devoted to collect data on epidemiology of FTD and its subtypes and to provide harmonization of procedures among Centers.