BACKGROUND:During Covid-19 pandemic, the Italian government adopted restrictive limitations and declared a national lockdown on March 9, which lasted until May 4 and produced dramatic consequences on people's lives. The aim of our study was to assess the impact of prolonged lockdown on behavioral and psychological symptoms of dementia (BPSD).METHODS:Between April 30 and June 8, 2020, we interviewed with a telephone-based questionnaire the caregivers of the community-dwelling patients with dementia who had their follow-up visit scheduled from March 9 to May 15 and canceled due to lockdown. Among the information collected, patients' BPSDs were assessed by the Neuropsychiatric Inventory (NPI). Non-parametric tests to compare differences between NPI scores over time and logistic regression models to explore the impact of different factors on BPSD worsening were performed.RESULTS:A total of 109 visits were canceled and 94/109 caregivers completed the interview. Apathy, irritability, agitation and aggression, and depression were the most common neuropsychiatric symptoms experienced by patients both at baseline and during Covid-19 pandemic. Changes in total NPI and caregiver distress scores between baseline and during lockdown, although statistically significant, were overall modest. The logistic regression model failed to determine predictors of BPSD worsening during lockdown.CONCLUSION:This is one of the first studies to investigate the presence of BPSD during SARS-CoV-2 outbreak and related nationwide lockdown, showing only slight, likely not clinically relevant, differences in BPSD burden, concerning mostly agitation and aggression, anxiety, apathy and indifference, and irritability.

Background The early detection of patients at risk of post-stroke cognitive impairment (PSCI) may help planning subacute and long-term care. We aimed to determine the predictivity of two screening cognitive tests on the occurrence of mild cognitive impairment or dementia in acute stroke patients. Methods A cognitive assessment within a few days of ischemic or hemorrhagic stroke was performed in patients consecutively admitted to a stroke unit over 14 months by means of the Clock Drawing Test (CDT) and the Montreal Cognitive Assessment-Basic (MoCA-B). Results Out of 191 stroke survivors who were non-demented at baseline, 168 attended at least one follow-up visit. At follow-up (mean duration ± SD 12.8 ± 8.7 months), 28 (18.9%) incident cases of MCI and 27 (18%) cases of dementia were recorded. In comparison with patients who remained cognitively stable at follow-up, these patients were older, less educated, had more comorbidities, a higher score on the National Institutes of Health Stroke Scale (NIHSS) at admission, more severe cerebral atrophy, and lower MoCA-B and CDT scores at baseline. In multi-adjusted (for age, education, comorbidities score, NIHSS at admission and atrophy score) model, a pathological score on baseline CDT (< 6.55) was associated with a higher risk of PSCI at follow-up (HR 2.022; 95% CI 1.025–3.989, p < 0.05) with respect to non-pathological scores. A pathological baseline score on MoCA-B (< 24) did not predict increased risk of cognitive decline at follow-up nor increased predictivity of stand-alone CDT. Conclusion A bedside cognitive screening with the CDT helps identifying patients at higher risk of PSCI.

INTRODUCTION:Cognitive impairment is a common and disabling consequence of stroke. Its prevalence, the best way to screen for it in the acute setting, and its relation with premorbid status have not been thoroughly clarified.MATERIALS AND METHODS:Ischemic and hemorrhagic stroke patients admitted to our stroke unit underwent a baseline assessment that included a clinical and neuroimaging assessment, two cognitive tests (clock-drawing test, CDT; Montreal Cognitive Assessment-Basic, MoCA-B) and measures of premorbid function (including the Clinical Dementia Rating Scale). A follow-up examination was repeated 3-4 months after the acute event.RESULTS:Two hundred and twenty-three patients (52.5% women, mean age ± SD 75.8 years ± 12.3) were evaluated. Prestroke cognitive impairment was present in 91 patients (40.8%). At follow-up, the prevalence of cognitive impairment was 49%, while its incidence among patients who did not have any prestroke cognitive impairment was 38.8%. Of the originally admitted 223 patients (71 were lost to follow-up), only 60 (26.9%) were still cognitively intact at follow-up. On regression analysis, age and baseline CDT were associated with worsening of cognitive status at follow-up. In patients without cognitive impairment at baseline, a cutoff of 23 for MoCA-B and of 8.7 for CDT scores predicted the diagnosis of post-stroke cognitive impairment with sufficient accuracy.DISCUSSION AND CONCLUSION:Prestroke and post-stroke cognitive impairment affect a large proportion of patients with stroke. Our findings suggest that a neuropsychological screening during the acute phase might be predictive of the development of post-stroke cognitive impairment.

Background The number of migrants with dementia in Italy might increase considerably over the coming years due to the increasing flow of immigration and the aging of the population. Aims We retrospectively registered rate and characteristics of demented migrant outpatients referred to one hospital in Milan from 2001 to 2017. Methods Information about country of origin of migrants attending general neurology and memory clinics was obtained from their Italian tax code. Socio-demographic, cultural, and clinical characteristics were derived from their medical records. Results Migrants with cognitive decline represented a minimal fraction (3.1%) of demented outpatients, but a grow rate of 400% was registered within the period of observation. A linguistic barrier resulted as the main obstacle for the application of available diagnostic tools for dementia. Discussion/conclusion Given the above-reported data, the implementation of strategies (such as transcultural diagnostic instruments) and policies dedicated to this growing health problem appears a priority for our health systems.

To assess the diagnostic accuracy of the free and cued selective reminding test (FCSRT) for the development of Alzheimer’s disease (AD) in people with mild cognitive impairment (MCI).

Introduction: Social isolation and living alone have been associated with negative outcomes, especially in the older population. We aim to investigate the effect of living alone on the development of dementia in people with mild cognitive impairment (MCI). Materials and Methods: In this longitudinal study, we enrolled 345 outpatients with MCI evaluated at baseline through a clinical and neuropsychological protocol. Data on living situation (living alone vs. living with someone) were also collected. The development of dementia at follow-up was the outcome of the study. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression analyses. Laplace regression was used to model the time-to-dementia diagnosis as a function of living situation. Results: During the follow-up time (mean [SD]: 2.8 [2.2] years), 172 (50%) participants developed dementia. After controlling for age, sex, years of education, MCI subtype, presence of comorbidities, and antidepressant therapy, people with MCI living alone were more likely to develop dementia (HR: 1.5; 95% CI: 1.1-2.1), when compared to those living with someone. In addition, participants with MCI living alone were diagnosed with dementia 1 year earlier than those living with someone (P = .012). Conclusion: Living alone increases by 50% the risk of developing dementia and anticipates by 1 year the diagnosis in people with MCI. These results, in line with findings of previous population-based studies, emphasize the pivotal role of the living situation in identifying a frailer share of the population at higher risk of dementia to which devote ad hoc assessment and care.

Dementia is one of the main causes of disability later in life. Interventions in support of patients with dementia aim at granting the highest level of independence in activities of daily living and at delivering the required facilities; formal and informal caregivers represent the interface between patients and health services. The aims of our study were to assess caregivers’ perceived needs and to relate them to their own socio-cultural features and to patients’ clinical characteristics. During three consecutive months, 50 caregivers of patients with dementia were interviewed about their needs in the assistance of subjects with dementia by means of three structured questionnaires (Caregiver Needs Assessment [CNA], Zarit Burden Inventory [ZBI], Neuropsychiatric Inventory–Questionnaire [NPI-Q]) and of two open-ended questions. Higher scores of CNA (suggestive of more needs) were associated with a major burden in caregiving and were related to a more severe behavioral and psychological profile of patients with dementia. ZBI was highly correlated with NPI distress score. Among caregivers, the children of patients reported more needs, particularly about information on disease and how to cope with it. CNA emerged as a complete and reliable instrument, with need for safety being the only item missing from the questionnaire and identified by means of the open-ended questions. Our results showed how the use of simple and brief instruments can increase the communication between health operators and caregivers and could thus improve the quality of formal and informal assistance.

Aims: The main aim of this multicentric longitudinal project is to investigate the specificity and sensitivity of three memory tests (FCSRT, STMBT, DMS48) proposed as cognitive marker for Alzheimer's disease (AD). Here, we report preliminary baseline data on healthy controls, people with MCI and patients with AD. Subjects and methods: Data collected on 13 AD, 16 MCI, 16 healthy older (HO) and 16 healthy younger (HY) adults were analysed. All participants underwent the three experimental tests along with a standard neuropsychological evaluation in one single session. Results: For the FCSRT, a three-way ANOVA with GROUP as the between-subjects factor and TASK (free, cued) and TIME (immediate, delayed) as within-subjects measures revealed a significant effect of GROUP (HY = HO > MCI > AD; p free, ; p delayed; p MCI > AD; p paired = abstract; p HO > MCI > AD; p 3; p binding; p< .001) and a significant interaction between STIMULUS and GROUP (p= .003). Discussion: The present report study shows reports for the first time a comparison across Controls, MCI and AD on three memory tests proposed as cognitive markers for AD. For the FCSRT both the timing of recall and the presence of a cue are relevant factors to influence patient performances. For the DMS48 the most sensitive indexes to differentiate between controls and patients are the unpaired and abstract items, while for the STMBT the binding condition is more affected in patients are regardless of the number of items presented are. These preliminary data are encouraging in confirming that these tests may offer an aid to diagnosis of early AD, but a larger sample and longitudinal data are needed to address the main research question of this planned study. *** References: Barbeau, E, Didic, M, Tramoni, E, Felician, O, Joubert, S, Sontheimer, A, Ceccaldi, M, Poncet, M. (2004). Evaluation of visual recognition memory in MCI patients. Neurology 62, 1317-1322. Frasson P, Ghiretti R, Catricala E, Pomati S, Marcone A, Parisi L, Rossini PM, Cappa SF, Mariani C, Vanacore N, Clerici F (2011) Free and cued selective reminding test: an Italian normative study. Neurological Sciences 32:1057-1062 Parra MA, Abrahams S, Fabi K, Logie R, Luzzi S, Della Sala S (2009) Short-term memory binding deficits in Alzheimer's disease. Brain 132:1057-1066

Aim: To assess memory impairment insight as a predictor of dementia and Alzheimer's disease (AD) in amnestic mild cognitive impairment (MCI). Methods: To verify whether the awareness of memory impairment assessed by Geriatric Depression Scale (GDS) was associated with the risk of progression to dementia and AD in a cohort of MCI, we used a Cox regression model adjusted for age, sex, education, subtypes of amnestic MCI, Mini-Mental State Examination, Cumulative Illness Rating Scale severity index, and apolipoprotein E genotype. Results: During a follow-up of 27.7 (20.8) months, 205 (63.3%) of 324 patients with amnestic MCI progressed to dementia, including 141 to AD. No association was found in the unadjusted, partially adjusted (for sociodemographic variables), and fully adjusted multivariate Cox analysis between the awareness of memory impairment and the progression to dementia and AD. Discussion: Awareness or anosognosia of memory deficits, identified by GDS, is not useful to predict progression to dementia of patients with amnestic MCI.

Repeated traumatic brain injuries have a negative impact on brain integrity and cognition. It was hypothesized that they could trigger the AD amyloidogenic cascade or they could represent a peculiar clinical entity labelled as “chronic traumatic encephalopathy”, CTE. To contribute in the understanding of this controversy we describe the case of a boxer with early onset dementia, reporting biomarkers and neuropsychological assessment with the effort to differentiate the AD diagnosis and CTE. We discuss, for each element, it’s possible role with regard to the opposite diagnostic directions and we highlight, on the example of our probable CTE patient, the necessity of better defined diagnostic criteria for the chronic traumatic encephalopathy.

AIMS:Analysis of nutritional status and body composition in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI).METHODS:A cross-sectional study was performed in a University-Hospital setting, recruiting 59 patients with AD, 34 subjects with MCI and 58 elderly healthy controls (HC). Nutritional status was assessed by anthropometric parameters (body mass index; calf, upper arm and waist circumferences), Mini Nutritional Assessment (MNA) and body composition by bioelectrical impedance vector analysis (BIVA). Variables were analyzed by analysis of variance and subjects were grouped by cognitive status and gender.RESULTS:Sociodemographic variables did not differ among the three groups (AD, MCI and HC), except for females' age, which was therefore used as covariate in a general linear multivariate model. MNA score was significantly lower in AD patients than in HC; MCI subjects achieved intermediate scores. AD patients (both sexes) had significantly (p<0.05) higher height-normalized impedance values and lower phase angles (body cell mass) compared with HC; a higher ratio of impedance to height was found in men with MCI with respect to HC. With BIVA method, MCI subjects showed a significant displacement on the RXc graph on the right side indicating lower soft tissues (Hotelling's T2 test: men = 10.6; women = 7.9;p < 0,05) just like AD patients (Hotelling's T2 test: men = 18.2; women = 16.9; p<0,001).CONCLUSION:Bioelectrical parameters significantly differ from MCI and AD to HC; MCI showed an intermediate pattern between AD and HC. Longitudinal studies are required to investigate if BIVA could reflect early AD-changes in body composition in subjects with MCI.

The prognostic value of mild cognitive impairment (MCI) is being questioned, with some MCI subjects reverting to normal cognition (NC). The reversion rate varies mostly depending on the study design, the setting, and both MCI and NC definitions. Previous studies have focused on the profile of subjects who revert to NC, but the role of comorbidities has not been entirely investigated. We aimed to evaluate the proportion of MCI subjects who revert to NC in a memory clinic context, focusing on the role of comorbidities. Between 2004 and 2013, 374 MCI subjects were recruited. During a mean time of 32 ± 25.5 months, 21 subjects (5.6%) reverted to NC. Subjects who reverted to NC were younger (p = 0.0001), more educated (p = 0.0001), had a better global cognition (p = 0.0001), as assessed by the Mini-Mental State Examination (MMSE) and suffered from more comorbidities (p = 0.002), as assessed by Cumulative Illness Rating Scale (CIRS) than those who developed dementia. The Cox Regression Model, constructed to adjust for the confounders, showed that the higher were the MMSE (HR = 1.83, CI 95%: 1.07-3.11) and the CIRS score (HR = 1.3, CI 95% 0.88-1.92) at baseline, the higher was the probability of returning to NC than developing dementia, though the last association was not significant. Subjects who reverted to NC were more frequently affected by respiratory (p = 0.002), urologic (p = 0.012), and psychiatric (p = 0.012) diseases. The cognitive performance of subjects with medical comorbidities could benefit from preventive strategies aimed at treating the underlying diseases.

Aims: To examine the relationship between body mass index (BMI) and progression to dementia and Alzheimer's disease (AD) in mild cognitive impairment (MCI). Materials and Methods: Two hundred and twenty-eight MCI subjects (mean age 74.04 ± 6.94 years; 57% female) from a memory clinic were followed for 2.40 ± 1.58 years. Baseline height and weight were used to calculate the BMI. The main outcome was progression to dementia (DSM-IV criteria) and AD (NINCDS-ADRDA criteria). Cox proportional hazard models were used to assess the longitudinal association of BMI with dementia and AD, adjusting for a comprehensive set of covariates, including vascular risk factors/diseases and neuroimaging profiles. Results: Out of 228 subjects with MCI, 117 (51.3%) progressed to dementia. Eighty-nine (76%) of the incident dementia cases had AD. In both unadjusted and multi-adjusted models, a higher BMI was associated with a reduced risk of dementia (multi-adjusted HR 0.9; 95% CI 0.8-0.9) and AD (multi-adjusted HR 0.9; 95% CI 0.8-0.9). Being underweight increased the risk of all types of dementia (multi-adjusted HR 2.5; 95% CI 1.2-5.1) but was not specifically associated with AD (multi-adjusted HR 2.2; 95% CI 0.9-5.3). Conclusions: BMI predicted progression of MCI to dementia and AD. In particular, a higher BMI was associated with a lower risk of dementia and AD, and underweight was associated with a higher risk of dementia. BMI assessment may improve the prognostic accuracy of MCI in clinical practice.

BACKGROUND:Weight loss is common in people with Alzheimer's disease (AD) and it could be a marker of impending AD in Mild Cognitive Impairment (MCI) and improve prognostic accuracy, if accelerated progression to AD would be shown. AIMS:To assess weight loss as a predictor of dementia and AD in MCI. METHODS:One hundred twenty-five subjects with MCI (age 73.8 ± 7.1 years) were followed for an average of 4 years. Two weight measurements were carried out at a minimum time interval of one year. Dementia was defined according to DSM-IV criteria and AD according to NINCDS-ADRDA criteria. Weight loss was defined as a ≥4% decrease in baseline weight. RESULTS:Fifty-three (42.4%) MCI progressed to dementia, which was of the AD-type in half of the cases. Weight loss was associated with a 3.4-fold increased risk of dementia (95% CI = 1.5-6.9) and a 3.2-fold increased risk of AD (95% CI = 1.4-8.3). In terms of years lived without disease, weight loss was associated to a 2.3 and 2.5 years earlier onset of dementia and AD. CONCLUSIONS:Accelerated progression towards dementia and AD is expected when weight loss is observed in MCI patients. Weight should be closely monitored in elderly with mild cognitive impairment.

Background: Leisure activities, particularly exercise, play a protective role against dementia in healthy people, but it is unknown if this protective effect could be generalized to subjects with mild cognitive impairment (MCI).Objective: To investigate the influence of leisure activities on the risk of progression of MCI to dementia.Methods: 176 MCI subjects attending a memory clinic underwent a standardized lifestyle questionnaire between October 2007 and May 2010. Social, cognitive, and physical scores were derived based on the assiduity of interpersonal contacts and on the frequency of participation in individual leisure activities. Subjects were requested to return every 12 months for dementia surveillance. The outcome measure was the risk of dementia associated with social, cognitive, and physical scores.Results: Over a median follow-up time of 2.59 year, 92 (52.2%) MCI subjects developed dementia. Subjects with physical scores in the highest third had a lower risk (HR 0.44; 95% CI 0.23-0.85) of dementia compared with those in the lowest third. No association was found between cognitive or social scores and the risk of dementia.Conclusion: To our knowledge, this is the first prospective clinical study which demonstrates that high levels of participation in physical leisure activities are associated with reduced risk of dementia in subjects with MCI. In line with findings coming from community-based studies on healthy elderly, our finding suggests that the protective role of exercise against the development of dementia can be generalized to MCI subjects seen in clinical practice. Clinicians should encourage MCI subjects to participate in physical leisure activities.

Mutations in triggering receptor expressed on myeloid cells gene (TREM2) have previously been associated with Nasu-Hakola disease. Recent evidence highlighted an association between rare functional variants in TREM2 and Alzheimer's disease (AD) or Frontotemporal Lobar Degeneration (FTLD). The aim of this study has been to test TREM2 variants as susceptibility factors for FTLD and AD. Direct sequencing has been performed in an Italian population consisting of 75 patients diagnosed clinically with FTLD, 607 with AD, and 612 healthy age-matched controls. Four FTLD patients (5.3%) and twelve AD patients (2%) were carriers, in heterozygosis, of different variants. In particular, one FTLD patient was a carrier of the T66M mutation, which in homozygosis leads to Nasu Hakola disease. One FTLD patient and five AD patients were carriers of the rare variant R47H, previously associated with the development of AD. Lastly, two FTLD and two AD patients were carriers of the variant R62H, previously reported as a benign variant. Three more AD patients were carriers of Q33X mutation, that in homozygosis state leads to Nasu Hakola disease, whereas another one was carrier of the rare variant D87N. Lastly, a novel non pathological variant was found in one AD patient. TREM2 could likely act as risk factor for FTLD and AD. Further studies involving a larger size population are required to drawn definitive conclusions. Patients carrying these TREM2 variants could have a peculiar different pathogenic disease mechanism as compared with non-carriers, possibly overlapping with the Nasu-Hakola disease.