Normative data beyond the total scores: a process score analysis of the Rey's 15 word test in healthy aging and Alzheimer's Disease.

BACKGROUND: The Rey's 15 words test is currently the most frequently used task in Italy to detect memory deficits in AD. The current standardised version is however quite outdated and lacks some cognitive indexes which may highlight problems in recall or encoding processes. The aim of the study was to update the normative data of the test and to consider some variables which were not accounted for in the original study, that is, recognition, learning rate and forgetfulness. We also adopted the process scores approach to ascertain the effects of serial position (primacy and recency). METHODS: Three hundred ninety-six healthy participants were recruited. To detect any variables useful for intercepting the early stages of dementia, a group of 208 patients in the very early stage of AD was also recruited. Linear models were used to calculate the corrections scores for age, education, and gender, and ROCs were used to calculate cut-offs based on the maximum sum of sensitivity and specificity and the positive and negative predictive values. RESULTS: All main indexes showed excellent Area Under the Curve (0.90-1), strong sensitivity and PPVs for distinguishing between the HCs and AD participants. However, the Intrusions index performed poorly in all parameters. CONCLUSION: The study provides updated, normative data which may be reliably used as a cognitive marker to detect early AD. The strength of the study is the large sample size and the number of indexes which make it possible to explore the utility of memory test process scores.

Migrants seeking help for cognitive disturbances: exploratory data from an Italian memory clinic.

INTRODUCTION: The phenomenon of dementia occurring in migrants and minority groups constitutes an emerging issue for Western countries. Nevertheless, it has been poorly explored from the perspective of "real-world" clinical services. We aimed to quantify the number of migrants from LMIC attending an Italian university memory clinic and to document its modifications over time. METHODS: All the subjects undergoing a first neurological and cognitive assessment between 2001 and 2017 were considered for the present analyses. RESULTS: The proportion of subjects from LMIC performing a first cognitive evaluation was found to remain substantially stable between 2001 and 2017. No statistically significant difference was found between "HIC" and "LMIC" individuals with regard to sociodemographic and clinical characteristics. CONCLUSION: These findings seem to indicate that cognitive disorders in LMIC migrants still constitute a marginal public health issues for Italian dementia services. Nevertheless, the identification of eventual sociocultural and healthcare barriers may help to understand the real magnitude and relevance of this phenomenon.

Inappropriate Sexual Behaviors Among Community-Dwelling Patients with Dementia.

OBJECTIVE: Inappropriate sexual behaviors (ISBs) represent challenging and stressful manifestations of dementia and are highly burdening for patients, families, and healthcare providers. Nevertheless, ISBs have so far attracted limited clinical and scientific interest compared with other neuropsychiatric symptoms occurring in dementing illnesses. The authors aimed to systematically investigate the prevalence and characteristics of ISBs in a population of patients with dementia attending a memory clinic. METHODS: In this cross-sectional study, individuals with dementia attending our memory clinic were consecutively enrolled between January 2015 and February 2016. Participating subjects underwent a detailed medical history collection and a comprehensive cognitive, functional, and neuropsychiatric assessment. The presence of ISBs (in the previous 30 days) was investigated by the adoption of an ad hoc questionnaire, administered to informants. A logistic regression model was carried out to identify sociodemographic and clinical variables associated with ISBs. RESULTS: In the 195 patients (48.7% women) with dementia recruited for the study, ISBs were detected in 35 patients (17.9% of the total sample). The logistic regression model showed that male sex (OR: 5.14; 95% CI: 1.44-18.41) and anxiety (OR: 4.92; 95% CI: 1.44-16.84) were statistically significantly associated with the presence of ISBs. CONCLUSION: ISBs represent common manifestations of dementing illnesses. Given the significant burden of ISBs on patients and families and the impact on care management, their occurrence should always be investigated in the clinical care of individuals with dementia. For this purpose, specific screening/assessment tools should be properly designed and validated.

Sundowning in Patients with Dementia: Identification, Prevalence, and Clinical Correlates.

BACKGROUND: The term sundowning is used to describe the emergence or worsening of neuropsychiatric symptoms in late afternoon or early evening in people with dementia. OBJECTIVE: Our aim was to evaluate sundowning's prevalence and clinical manifestations among patients attending a tertiary memory clinic and to investigate its clinical and neuropsychological correlates. METHODS: Patients with dementia attending our memory clinic were enrolled in the study. Sundowning was identified through a specifically designed questionnaire. Sociodemographic and clinical features of sundowners and non-sundowners were compared, and a logistic regression was performed to identify the variables associated with the phenomenon. A subgroup of patients underwent a complete neuropsychological assessment. RESULTS: Among 184 recruited patients, 39 (21.2%) exhibited sundowning, mostly expressed as agitation (56.4%), irritability (53.8%), and anxiety (46.2%). Sundowners were significantly older, had a later dementia onset, exhibited more severe cognitive and functional impairment, more frequent nocturnal awakenings, and hearing loss relative to non-sundowners. They were also more likely to use anticholinergic medications and antipsychotics, and less likely to use memantine. In a multi-adjusted model, the factors significantly associated with sundowning were the Clinical Dementia Rating score (OR 3.88; 95% CI 1.39-10.90) and the use of memantine (OR 0.20; 95% CI 0.05-0.74). Participants with and without sundowning obtained similar results in single domain neuropsychological tests. CONCLUSION: Sundowning is commonly experienced by patients with dementia and appears as a multiply determined condition. Its presence should always be evaluated in clinical practice and a multidimensional approach should be adopted to identify its predictors.

The evaluation of capacity in dementia: ethical constraints and best practice. A systematic review.

The progressive ageing of a population leads to an increase in the number of people suffering from cognitive deterioration. This requires particular attention in terms of the necessity to assess these people's cognitive functions and their capacity to make decisions. The present systematic review analyses the clinical and ethical aspects of any assessment of capacity, with a specific focus on the capacity of the individual to give informed consent for medical treatment and also with regard to their testamentary capacity. The results indicate that the concepts of capacity, competence and decision-making need to be better clarified, ad-hoc devised tools are required and a multidisciplinary, clinical and legal approach to assessments of capacity needs to be adopted. This is crucial to guarantee that the two ethical principles of capacity assessment are adhered to: respect for an individual's autonomy and the protection of fragile individuals.

Dissociation between physical and mental number line bisection in right hemisphere brain damage.

To compare numeric quantities, humans make use of a 'mental number line' with smaller quantities located to the left of larger ones; it is unclear, however, whether orienting along the number line is like orienting along a physical line. We found that in brain-damaged subjects with defective leftward orienting, rightward deviation in the bisection of numeric and physical intervals is doubly dissociated. Deviation in numeric interval bisection was associated with prefrontal damage and spatial working memory deficit.

Plasma microRNA profiling distinguishes patients with frontotemporal dementia from healthy subjects.

The purpose of this study was to develop an easy and minimally invasive assay to detect a plasma miRNA profile in frontotemporal dementia (FTD) patients, with the final aim of discriminating between FTD patients and healthy controls (HCs). After a global miRNA profiling, significant downregulation of miR-663a, miR-502-3p, and miR-206 (p = 0.0001, p = 0.0002, and p = 0.02 respectively) in FTD patients was confirmed when compared with HCs in a larger case-control sample. Moreover, miR-663a and miR-502-3p showed significant differences in both genders, whereas miR-206, only in male subjects. To obtain a discriminating measure between FTD patients and HCs, we calculated a combined score of the 3 miRNAs by applying a Bayesian approach and obtaining a classifier with an accuracy of 84.4%. Moreover, for men, combined miRNA levels showed an excellent sensitivity (100%) and a good specificity (87.5%) in distinguishing FTD patients from HCs. All these findings open new hypotheses in the pathophysiology and new perspectives in the diagnosis of a complex pathology as FTD.

Contribution of right hemisphere to visual imagery: a visual working memory impairment?

Visual Imagery is the ability to generate mental images in the absence of perception, that is, We describe a patient, IM, who suffered from an acute ischemic stroke in the right anterior choroidal artery who appeared to demonstrate relatively isolated impairment in visual imagery. Her cognitive function, including her performance on tests of semantic function, was at ceiling, apart from a deficit in visual memory. IM failed in tasks involving degraded stimuli, object decision involving reality judgments on normal animals, and drawings from memory. By contrast, she was able to match objects seen from an unfamiliar viewpoint and to perform tasks of semantic and visual association. We hypothesize that IM has a visual working memory deficit that impairs her ability to generate full visual representations of objects given their names, individual feature, or partial representations. The deficit appears to be the result of damage to connections between the right thalamus and the right temporal lobe. Our findings may help to clarify the role of the thalamus in the cortical selective engagement processes that underlie working memory.

Use of neuropsychological tests for the diagnosis of dementia: a survey of Italian memory clinics.

AIM: Providing an overview of the neuropsychological tests used in Italian memory clinics (defined as Centers for Cognitive Disorders and Dementias-CCDD in Italy) for the diagnosis of cognitive disorders and dementias. METHODS: A total of 501 CCDD, out of all 536 active CCDD, were surveyed between February 2014 and August 2015 to verify the characteristics of the centres who performed a comprehensive neuropsychological assessment (NPA), defined as the administration of at least one test for verbal and visual episodic memory, attention, constructional praxis, verbal fluency and executive functions (minimum core tests-MCTs), as part of the diagnostic process. RESULTS: A total of 45.7% of Italian CCDD performed a comprehensive MCT as part of the diagnostic process. The logistic regression model showed that the probability of including at least one psychologist in the team was higher in the CCDD that reported using a comprehensive NPA (OR 4.55; 95% CI 2.92 to 7.1), that CCDD in Southern Italy had a lower probability of using an MCT (OR 0.56; 95% CI 0.35 to 0.89) and that the use of an MCT was higher in university/Institute for Scientific Research and Healthcare CCDD (OR 10.97; 95% CI 3.85 to 31.25). CONCLUSION: Almost half of the CCDD administered a set of MCTs; while the remaining centres only performed few tests or screening procedures. The neuropsychological tests used in Italian CCDD were comparable with those used in other European countries. Performing a comprehensive NPA remains the best way to assess and monitor cognitive deficits over time, thus further debate on the current status of NPAs in clinical practice is needed.

Circulating miR-127-3p as a Potential Biomarker for Differential Diagnosis in Frontotemporal Dementia.

Given the heterogeneous nature of frontotemporal dementia (FTD), sensitive biomarkers are greatly needed for the accurate diagnosis of this neurodegenerative disorder. Circulating miRNAs have been reported as promising biomarkers for neurodegenerative disorders and processes affecting the central nervous system, especially in aging. The objective of the study was to evaluate if some circulating miRNAs linked with apoptosis (miR-29b-3p, miR-34a-5p, miR-16-5p, miR-17-5p, miR-107, miR-19b-3p, let-7b-5p, miR-26b-5p, and 127-3p) were able to distinguish between FTD patients and healthy controls. For this study, we enrolled 127 subjects, including 54 patients with FTD, 20 patients with Alzheimer's disease (AD), and 53 healthy controls. The qRT-PCR analysis showed a downregulation of miR-127-3p in FTD compared to controls, while the levels of other miRNAs remained unchanged. Then, miR-127-3p expression was also analyzed in AD patients, finding a different expression between two patient groups. A receiver operating characteristic curve was then created for miR-127-3p to discriminate FTD versus AD (AUC: 0.8986), and versus healthy controls (AUC: 0.8057). In conclusion, miR-127-3p could help to diagnose FTD and to distinguish it from AD.

[Use of neuropsychological tests in the Cronos Project]. / L'uso degli strumenti neuropsicologici nell'ambito del Progetto Cronos.

Within the Cronos Project, 503 Alzheimer's disease units were activated throughout the country. In June/July 2002 a questionnaire was sent to all Alzheimer's disease units to collect data on neuropsychological tests utilised in the diagnostic process of dementias. Only 196 of Alzheimer's disease units that have responded to the questionnaire (196/392) declare to utilize neuropsychological test while 97.8% use the mini mental state examination. This paper aims to collect, for the first time in Italy, data on use of the neuropsychological tests in the specialist units on dementia and to propose a discussion on the reliability of neuropsychological instruments.

Sociodemographic and Clinical Changes Over Time of Individuals Evaluated for Cognitive Disturbances: Good or Bad News?

In recent years, "prevention" and "early diagnosis" have been growingly discussed and explored in the field of cognitive disorders. Such increased attention to cognitive disturbances and neurodegenerative conditions may constitute a key step for achieving early/timely diagnosis of dementing illnesses. At the same time, it may generate possible issues (such as a greater proportion of negative diagnostic procedures with potential misuse of resources) that should be acknowledged by health care systems. In this report, we present exploratory analyses aimed at investigating the sociodemographic and clinical changes over time of all the individuals who have been cognitively assessed in a Memory Clinic between 2002 and 2014. Overall, individuals evaluated for cognitive disturbances have gradually become younger, more educated, and less impaired in cognitive and physical functions at their first cognitive assessment. To date, nearly 1 of 4 individuals completing a neuropsychological evaluation has no objective cognitive deficits, thus presenting subjective cognitive complaints. Based on these findings, the development and implementation of strategies for improving the referral to memory clinics is strongly needed.

SORL1 Gene is Associated with the Conversion from Mild Cognitive Impairment to Alzheimer's Disease.

Several studies have established the sortilin-related receptor gene (SORL1) as a susceptibility locus for Alzheimer's disease (AD). Single nucleotide polymorphisms of SORL1 reported in literature as being associated with AD were investigated in an Italian case-control data set, and their role as a risk factor of conversion to AD was studied in an independent sample of subjects diagnosed with mild cognitive impairment (MCI) at baseline. rs641120, rs2070045, and rs1010159 were genotyped in 734 subjects diagnosed with AD (n = 338) and MCI (n = 181) and in healthy controls (n = 215). Our results confirmed the association between rs641120 and AD (p = 0.01). In the MCI cohort, rs1010159 was associated with conversion to AD (HR = 1.56, p = 0.002). Taken together, these findings confirm that SORL1 is associated with AD and might be a potential tool for identifying MCI subjects at high risk of conversion to AD.

Presenilin 2 mutation R71W in an Italian early-onset sporadic Alzheimer's disease case.

Mutations in the presenilin 2 (PSEN2) gene are less commonly identified as genetic causes of early-onset familial Alzheimer's disease than mutations in the amyloid precursor protein (APP) and the presenilin 1 (PSEN1) genes. In fact, only 23 different mutations in the PSEN2 gene have been described in the literature. This paper deals with a sporadic case of a 55 year-old subject bearing an amino acid substitution from arginine to tryptophan at codon 71 of PSEN2 and presenting a peculiar early-onset Alzheimer's disease phenotype.

A novel mutation in the predicted TMIII domain of the PSEN2 gene in an Italian pedigree with atypical Alzheimer's disease.

Alzheimer's disease (AD) is characterized by accumulation of toxic amyloid-beta (Abeta) in the brain, with neuronal death, and an associated increased Abeta(42/40) ratio. Several mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid-beta precursor protein are involved in the etiology of familial AD (FAD); these mutations alter the Abeta(42/40) ratio and promote apoptosis. We describe an Italian pedigree linked to a novel mutation (S175C) at the third transmembrane domain of PSEN2. Clinical phenotype in these individuals is characterized by fast cognitive decline with progressive memory impairment, early involvement of executive functions, behavioral disturbances, and extrapyramidal signs.

Spatial orienting biases in the decimal numeral system.

Humans map numbers upon a mental number line (MNL) on which small integers are placed to the left of larger ones [1-9]. Here, we show that human adults systematically shift the subjective midpoints of number intervals away from the borders separating contiguous tens along the MNL. Number intervals are erroneously bisected further to the right the closer they are to the left starting point of the tens and further to the left the closer they are to the right endpoint of the tens. Similarly, right-brain-damaged patients neglecting the left side of the MNL [10-12] show enhanced pathological rightward deviation in the bisection of number intervals located toward the left starting point of the tens and reduced deviation for intervals located toward the right endpoint of the tens. These data disclose the effects that the recursive grouping of symbolic decimal numerals within the tens has brought on the phylogenetically and ontogenetically foregoing spatial representation of magnitudes [13-16].