Giulia Grande

Physical Activity Reduces the Risk of Dementia in Mild Cognitive Impairment Subjects: A Cohort Study

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.

Reversible Mild Cognitive Impairment: The Role of Comorbidities at Baseline Evaluation.

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.

Nutritional status and body composition by bioelectrical impedance vector analysis: A cross sectional study in mild cognitive impairment and Alzheimer’s disease

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.

Role of anticholinergic burden in primary care patients with first cognitive complaints

Drugs with anticholinergic properties might have a negative impact on cognition, but findings are still conflicting. The association was evaluated between anticholinergic drugs and cognitive performance in primary care patients with first cognitive complaints.

PRNP P39L variant is a rare cause of frontotemporal dementia in Italian population

The missense P39L variant in the prion protein gene (PRNP) has recently been associated with frontotemporal dementia (FTD). Here, we analyzed the presence of the P39L variant in 761 patients with FTD and 719 controls and found a single carrier among patients. The patient was a 67-year-old male, with a positive family history for dementia, who developed apathy, short term memory deficit, and postural instability at 66. Clinical and instrumental workup excluded prion disease. At MRI, bilateral frontal lobe atrophy was present. A diagnosis of FTD was made, with a mainly apathetic phenotype. The PRNP P39L mutation may be an extremely rare cause of FTD (0.13%).

Listeria brain abscesses during administration of mycophenolate mofetil for systemic lupus erythematosus: a case report.

Listeria monocytogenes is an important pathogen in immunocompromised individuals [1]. The most common central nervous system manifestation is meningitis, other, less common, are rhombencephalitis, meningoencephalitis and cerebritis [1]. Brain abscess, usually solitary [2], is a rare complication [1]. The main features of listerial brain abscesses are the bacteremia and their typical locations in pons, thalamus, or medulla [1]. Treatment of choice is ampicillin but also penicillin, gentamicin, trimethoprim/ sulfamethoxazole or meropenem can be used.

Living Alone and Dementia Incidence : A Clinical-Based Study in People With Mild Cognitive Impairment

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.

Why Mild Cognitive Impairment Should Not Be Approached as a Disease: Reply to Iraqi and Hughes

1. Canevelli M, Grande G, Lacorte E, et al. Spontaneous reversion of mild cognitive impairment to normal cognition: A systematic review of literature and metaanalysis. J Am Med Dir Assoc 2016;17:943e948. 2. Petersen RC. Mild cognitive impairment. N Engl J Med 2011;364:2227e2234. 3. Busse A, Hensel A, Guhne U, et al. Mild cognitive impairment: Long-term course of four clinical subtypes. Neurology 2006;67:2176e2185. 4. Plassman BL, Langa KM, Fisher GG, et al. Prevalence of cognitive impairment without dementia in the United States. Ann Intern Med 2008;148: 427e434. 5. Lopez OL, Jagust WJ, DeKosky ST, et al. Prevalence and classification of mild cognitive impairment in the cardiovascular health study cognition study: Part 1. Arch Neurol 2003;60:1385e1389.

Self-Awareness for Memory Impairment in Amnestic Mild Cognitive Impairment: A Longitudinal Study

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.

Risk Factors and Prevention in Alzheimer’s Disease and Dementia

Along with global aging, the number of people suffering from dementia and Alzheimer’s disease (AD) will dramatically increase with burdensome consequences at both individual and societal levels. Since so far no effective curative drugs have been found, the identification of modifiable factors to reduce the risk of cognitive decline remains a public health priority. Up to one-third of AD cases worldwide can be attributable to the presence of seven potentially modifiable risk factors: physical inactivity, smoking, midlife hypertension and obesity, DM, depression, and low level of education. Therefore, it might be possible to substantially reduce AD occurrence through public health interventions promoting activities enhancing cognitive reserve and healthy lifestyles. In this chapter, we summarize the major findings concerning risk and protective factors for dementia and AD, based on current epidemiological evidence from observational and interventional studies. We also discuss the impact of ongoing interventional studies testing the effect of preventive measures for dementia and AD.