One of the earliest pathological features characterizing Alzheimer’s disease (AD) is the loss of dendritic spines. Among the many factors potentially mediating this loss of neuronal connectivity, the contribution of Rho-GTPases is of particular interest. This family of proteins has been known for years as a key regulator of actin cytoskeleton remodeling. More recent insights have indicated how its complex signaling might be triggered also in pathological conditions. Here, we showed that the Rho-GTPase family member Rac1 levels decreased in the frontal cortex of AD patients compared to non-demented controls. Also, Rac1 increased in plasma samples of AD patients with Mini-Mental State Examination < 18 compared to age-matched non demented controls. The use of different constitutively active peptides allowed us to investigate in vitro Rac1 specific signaling. Its activation increased the processing of amyloid precursor protein and induced the translocation of SET from the nucleus to the cytoplasm, resulting in tau hyperphosphorylation at residue pT181. Notably, Rac1 was abnormally activated in the hippocampus of 6-week-old 3xTg-AD mice. However, the total protein levels decreased at 7-months. A rescue strategy based on the intranasal administration of Rac1 active peptide at 6.5 months prevented dendritic spine loss. This data suggests the intriguing possibility of a dual role of Rac1 according to the different stages of the pathology. In an initial stage, Rac1 deregulation might represent a triggering co-factor due to the direct effect on Aβ and tau. However, at a later stage of the pathology, it might represent a potential therapeutic target due to the beneficial effect on spine dynamics.

A growing number of studies are attempting to understand how effective cognitive interventions may be for patients with amnestic mild cognitive impairment (aMCI), particularly in relation to their memory problems. The present study aimed to explore the benefits of a working memory (WM) training program in aMCI patients. Patients (N = 20) were randomly assigned to two training programs: the experimental group practiced with a verbal WM task, while the active control group conducted educational activities on memory. Results showed that the aMCI patients completing the WM training obtained specific gains in the task trained with some transfer effects on other WM measures (visuospatial WM) and on processes involved in or related to WM, e.g. fluid intelligence (the Cattell test) and long-term memory. This was not the case for the aMCI control group, who experienced only a very limited improvement. This pilot study suggests that WM training could be a valuable method for improving cognitive performance in aMCI patients, possibly delaying the onset of Alzheimer's disease.

Objective The goal of the present work, based on a collaborative research registry in Italy (the Salento-Brescia Registry), was to assess the incidence of frontotemporal lobar degeneration (FTLD) and to define the frequencies of different FTLD phenotypes in the general population. Methods The study was conducted from January 1, 2017, to December 31, 2017, in 2 Italian provinces: Lecce (in Puglia) in the south (area 2,799.07 km², inhabitants 802,082) and Brescia (in Lombardy) in the north (area 4,785.62 km², inhabitants 1,262,678). During the study period, all new cases of FTLD (incident FTLD) were counted, and all patients9 records were reviewed. The incidence was standardized to the Italian general population in 2017. Results In the 2 provinces, 63 patients with FTLD were diagnosed. The incidence rate for FTLD was 3.05 (95% confidence interval [CI] 2.34–3.90) per 100,000 person-years (py), while the age-sex standardized incidence rate was 3.09 (95% CI 2.95–3.23) per 100,000 py. In the Italian population, the lifetime risk was 1:400. There was a progressive increase in FTLD incidence across age groups, reaching its peak in the 75- to 79-year-old group, with an incidence rate of 15.97 (95% CI 8.94–26.33) per 100,000 py. The behavioral variant of frontotemporal dementia was the most common phenotype (37%). No difference in crude incidence rate between the 2 provinces was observed. Conclusion FTLD is a more common form of dementia than previously recognized, with a risk spanning in a wide age range and with maximum incidence in the mid-70s. Improved knowledge of FTLD epidemiology will help to provide appropriate public health service policies.

Background: Early onset dementias (EOD) are rare neurodegenerative dementias that present before 65 years. Genetic factors have a substantially higher pathogenetic contribution in EOD patients than in late onset dementia. Objective: To identify known

A large portion of frontotemporal lobar degeneration (FTLD) patients has a family history of disease and the presence of a pathogenic mutation confirms the clinical diagnosis. Recently, standardized criteria to evaluate FTLD pedigree, based on first-