Sundowning means the emergence or worsening of neuropsychiatric symptoms (NPS) in the late afternoon or early evening. This syndrome has been recognized since a long time in the field of dementing illnesses and is well known among most of health-care providers involved in the assistance of people with dementia. Indeed, it represents a common manifestation among persons with dementia and is associated with several adverse outcomes (such as institutionalization, faster cognitive worsening, and greater caregiver burden). Its occurrence and phenotypic characteristics may be influenced by diverse neurobiological, psychosocial, and environmental determinants. Moreover, it may pose diagnostic challenges in relation to other common causes of behavioral disruptions. Beside these considerations, this phenomenon has so far drawn limited clinical and scientific interest compared to other specific NPS occurring in dementias, as indicated by the lack of commonly agreed definitions, specific screening/assessment tools, and robust estimates on its prevalence. Accordingly, no randomized controlled trial specifically investigating the effectiveness of pharmacological and non-pharmacological strategies in managing this condition among demented patients has been yet conducted. In the present narrative review, we present and discuss available evidence concerning sundowning occurring in people with dementia. A special focus is given to its definitions, pathophysiological determinants, and clinical relevance, as well as to the clinical and therapeutic approaches required for its management in the daily practice.

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CT in patients with AD showed a rate of thinning greater than what could be expected during the natural course of aging.

Introduction Current prescribing guidelines for the antipsychotic amisulpride are based largely on pharmacokinetic (PK) studies in young adults, and there is a relative absence of data on older patients, who are at greatest risk of developing adverse events.Methods This study aimed to develop a population PK model for amisulpride specifically in older people, by combining data from a richly sampled phase 1, single (50 mg) dose study in healthy older people (n = 20, 65–79 years), with a clinical dataset obtained during off label, low-dose (25–75 mg daily) amisulpride prescribing in older people with Alzheimer’s disease (AD) (n = 25, 69–92 years), as part of an observational study.Results After introducing a scaling factor based on body weight, age accounted for 20 % of the inter-individual variability in drug clearance (CL), resulting in a 54 % difference in CL between those aged 65 and those aged 85 years, and higher blood concentrations in older patients.Discussion These findings argue for the consideration of age and weight-based dose stratification to optimise amisulpride prescribing in older people, particularly in those aged 85 years and above.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-016-4379-6) contains supplementary material, which is available to authorized users.

The frailty construct has increasingly been adopted in the field of cognitive disorders. The aim of the present study was to measure frailty in a cohort of individuals with mild cognitive impairment (MCI) and to explore whether frailty measures may consent to predict the risk of conversion to dementia. We retrospectively reviewed the clinical charts of outpatients with amnesic MCI (aMCI) consecutively recruited at our Department, and followed-up for 5 years. Individual frailty status was measured by means of a frailty index (FI) consisting of 39 deficits (including signs, symptoms, diagnoses, and disabilities). Univariate analyses were used to compare the socio-demographic and clinical characteristics between subjects converting or not converting to probable Alzheimer’s disease (AD) dementia over the follow-up. Risk for conversion to AD dementia was assessed using Cox regression models. Ninety-one subjects with aMCI (mean age 72.7, SD 7.1 years; women 49.5%) were consecutively recruited over a period of 12 months. Low levels of frailty were documented in the sample (mean FI score 10.0, SD 5.3). A statistically significant correlation between age and FI was observed. Overall, 58 participants converted to AD dementia over time. The Cox regression analysis showed that age (HR: 1.04, 95% CI: 1.00–1.08), male sex (HR: 0.52, 95% CI: 0.30–0.91), Mini–Mental State Examination score (HR: 0.85, 95% CI: 0.77–0.94), and FI (HR: 1.11, 95% CI: 1.05–1.18) were all significantly associated with the probability of MCI conversion. Individual’s frailty status may increase the risk of conversion from a condition of MCI to overt AD dementia. The adoption of constructs comprehensively reflecting the biological decline of the aging subject may add useful estimates and information in the clinical approach to cognitive disorders.