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.

Clinical and radiological features of posterior cortical atrophy (PCA) in a GRN mutation carrier: a case report.

BACKGROUND AND PURPOSE: Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome, defined by a distinctive clinical-radiological profile, with Alzheimer's disease (AD) pathology accounting for the majority of cases. The aim of this report was to present the case of a patient with impairment of visual and constructional abilities as initial manifestations. METHOD: The patient underwent a multidimensional assessment, including neuropsychological evaluation, structural and functional imaging and genetic screening. RESULTS: Neurological and neuropsychological assessment showed an impairment of constructive and visuo-spatial skills, associated with dyscalculia, simultanagnosia, optic ataxia and oculomotor apraxia. In accordance with the latest consensus criteria, a diagnosis of PCA was made. Consistent with the clinical findings, structural and functional imaging showed a peculiar pattern of atrophy with primary involvement of right parieto-occipital cortices, whereas cerebrospinal fluid biochemical analysis did not reveal a profile compatible with AD pathology. Genetic screening identified a known pathogenic GRN mutation. CONCLUSION: We present a case of PCA in a GRN mutation carrier in whom a concomitant AD pathological process was excluded. Consequently, although lacking histological data, our case suggests GRN-related pathology causative of PCA. Through this report we provide further evidence for a new neurodegenerative pathway leading to PCA, extending the clinical spectrum of GRN-associated phenotypes.

Progression of behavioural disturbances in frontotemporal dementia: a longitudinal observational study.

BACKGROUND AND PURPOSE: Behavioural disturbances are the core features of frontotemporal dementia (FTD); however, symptom progression is still not well characterized during the entire course of the disease. The aim of the present study was to investigate behavioural symptoms at baseline and during the disease course in a large cohort of patients with behavioural variant FTD (bvFTD), non-fluent/agrammatic variant primary progressive aphasia (nfvPPA) and semantic variant primary progressive aphasia (PPA). METHODS: We evaluated 403 patients with FTD, 167 of whom had at least 1-year follow-up evaluation (for a total of 764 assessments). Behavioural symptoms were assessed and rated through the Neuropsychiatric Inventory (NPI) and Frontal Behavioural Inventory (FBI). Disease severity was evaluated through the Frontotemporal Lobar Degeneration -Clinical Dementia Rating scale (FTLD-CDR). Linear mixed models were used to model behavioural measures (NPI, FBI and the five FBI-behavioural core criteria scores) as a function of disease severity (FTLD-CDR score) and clinical phenotype. RESULTS: At baseline, patients with bvFTD showed more behavioural disturbances compared with those with nfvPPA (P = 0.004). Negative symptoms (apathy and loss of empathy) showed a trend to an increase throughout the course of the disease in both bvFTD and PPA (P < 0.001 until intermediate stages). Positive symptoms (disinhibition, perseverations and hyperorality) increased until intermediate phases (P < 0.001) followed by a progressive reduction in later phases, whereas they were less common in nfvPPA throughout the disease course. CONCLUSION: We demonstrated that behavioural disturbances differed in FTD and with disease severity. Positive symptoms appeared to improve in the advanced stages, highlighting the importance of taking into account the disease severity as outcome measure in clinical trials.

Modulating risky decision-making in Parkinson's disease by transcranial direct current stimulation.

BACKGROUND AND PURPOSE: Performance on gambling tasks in Parkinson's disease (PD) is of particular interest, as pathological gambling is often associated with dopamine replacement therapy in these patients. We aimed to evaluate the effects of transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex (DLPFC) in modulating gambling behaviour in PD. METHODS: We assessed the effects of cathodal tDCS over the right DLPFC during the Iowa Gambling Task in 20 patients with PD, compared with sham stimulation. We then conducted a second experimental design, assessing the effects of anodal tDCS over the right DLPFC. RESULTS: We observed that cathodal tDCS over the right DLPFC increased Iowa Gambling Task scores compared with sham stimulation. In the second experimental design, we did not find significant differences between anodal and sham tDCS. CONCLUSIONS: Cathodal tDCS over the right DLPFC possibly reduces the pathological overdrive in frontostriatal networks in patients with PD on dopaminergic medication, thus modulating impulsive and risky decision-making.

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.