Role of plasma phosphorylated neurofilament heavy chain (pNfH) in amyotrophic lateral sclerosis.

The phosphorylated neurofilament heavy chain (pNfH) is a promising biomarker in amyotrophic lateral sclerosis (ALS). We examined plasma pNfH concentrations in order to corroborate its role as a diagnostic and prognostic biomarker in ALS. Incident ALS cases enrolled in a population-based registry were retrospectively selected and matched by sex and age with a cohort of healthy volunteers. Plasma pNfH levels were measured by an ELISA kit and correlated with clinical parameters. Discrimination ability of pNfH was tested using receiving operating characteristic (ROC) curves. Kaplan-Meier (KM) analysis and Cox proportional hazard models were used for survival analysis. Plasma pNfH was significantly higher in patients compared to controls. An optimal cut-off of 39.74 pg/ml discriminated cases from controls with an elevated sensitivity and specificity. Bulbar-onset cases had higher plasma pNfH compared to spinal onset (p = 0.0033). Furthermore, plasma pNfH positively correlated with disease progression rate (r = 0.19, p = 0.031). Baseline plasma pNfH did not influence survival in our cohort. Our findings confirmed the potential utility of plasma pNfH as a diagnostic biomarker in ALS. However, further studies with longitudinal data are needed to corroborate its prognostic value.

The diagnostic accuracy of late-life depression is influenced by subjective memory complaints and educational level in an older population in Southern Italy.

The prevalence of late-life depression (LLD) depends on the study sample, measurements, and diagnostic approaches. We estimated the 30 item-Geriatric Depression Scale (GDS-30) accuracy against the gold standard LLD diagnosis made with the Semi-structured Clinical Diagnostic Interview for DSM-IV-TR Axis I Disorders, focusing on the prevalence of a late-life major depressive disorder (MDD), in a population-based sample of 843 subjects aged>65 years, subdivided into three groups: normal cognition, subjective memory complaints, and mild cognitive impairment. At the optimal cut-off score (≥4), the GDS-30 showed 65.1% sensitivity and 68.4% specificity for LLD (63% and 66% for late-life MDD, respectively). Using the standard cut-off score (≥10), the GDS-30 specificity reached 91.2%, while sensitivity dropped to 37.7%, indicating a lower screening accuracy [area under the curve(AUC):0.728, 95% confidence interval(CI):0.67-0-78]. The GDS-30 performance was associated with educational level, but not with age, gender, cognition, apathy, and somatic/psychiatric multimorbidity. For subjective memory complaints subjects, at the optimal cut-off score (≥7), the GDS-30 showed better discrimination performances (AUC=0.792,95%CI:0.60-0.98), but again the educational level affected the diagnostic performance. In subjective memory complaints subjects, symptom-based scales like the GDS-30 may feature a better performance for diagnosing depression in older age, but the GDS-30 seems to require adjustment to the patient's educational level.

The Role of Age on Beta-Amyloid1-42 Plasma Levels in Healthy Subjects.

Beta-amyloid (Aß) plaques have been observed in the brain of healthy elderlies with frequencies strongly influenced by age. The aim of the study is to evaluate the role of age and other biochemical and hematological parameters on Aß1-42 plasma levels in cognitively and neurologically normal individuals. Two-hundred and seventy-five normal subjects stratified by age groups (<35 years, 35-65 years, and >65 years) were included in the study. Aß1-42 plasma levels significantly correlated with age (rs = 0.27; p < 0.0001) in the whole sample, inversely correlated with age in the first age group (rs = -0.25, p = 0.01), positively correlated in the second group (rs = 0.22, p = 0.03), while there was no significant correlation in the older group (rs = 0.02, p = 0.86). Both age (ß-estimate = 0.08; p < 0.001) and cholesterol (ß-estimate = 0.03; p = 0.009) were significantly associated with Aß1-42 plasma level in multivariable analysis. However, only the association with age survived post hoc adjustment for multiple comparisons. The different effects of age on the Aß level across age groups should be explored in further studies to better understand the age-dependent variability. This could better define the value of plasma Aß as a biomarker of the Alzheimer neuropathology.

Reduction of Sniff Nasal Inspiratory Pressure (SNIP) as an Early Indicator of the Need of Enteral Nutrition in Patients with Amyotrophic Lateral Sclerosis.

Percutaneous endoscopic gastrostomy (PEG) is the standard procedure for feeding severely dysphagic patients with amyotrophic lateral sclerosis (ALS). It is associated with prolonged survival and improvement in quality of life. Nasal inspiratory pressure during a sniff (SNIP) is a respiratory test used extensively in ALS for the assessment of inspiratory muscle strength. In this study, we aimed to investigate the role of SNIP at baseline to predict PEG placement in ALS. Data from a clinical incident cohort of 179 ALS cases attending the multidisciplinary ALS unit of the University of Bari between April 2006 and December 2012 were retrospectively analysed. At baseline, patients underwent detailed neurological, nutritional and respiratory assessments, including measurements of SNIP and forced vital capacity (FVC). Patients were therefore followed up approximately every three to six months until they were able to attend the centre. The censoring date for the survival analysis was 15 April 2014, with PEG placement as the main outcome. Cox proportional hazard regression models were used to examine the association between SNIP and PEG placement, adjusted for possible confounders. During the follow-up period, 75 participants (42%) received PEG implant. PEG placement was more frequent (57% vs. 31%; p = 0.001) and earlier (after 11.6 ± 14.0 months from the first visit, vs. 23.3 ± 15.5 months; p < 0.0001) in the group of patients with baseline SNIP ≤ 40 cm H2O. Baseline SNIP was a predictor of PEG placement even after correction for multiple potential confounders (HR 0.98; 95% CI: 0.96-0.99; p = 0.02). To conclude, the present study showed that SNIP at baseline is an early indicator of disease progression and therefore of the need for enteral nutrition in ALS.

Exploring dementia and neuronal ceroid lipofuscinosis genes in 100 FTD-like patients from 6 towns and rural villages on the Adriatic Sea cost of Apulia.

Frontotemporal dementia (FTD) refers to a complex spectrum of clinically and genetically heterogeneous disorders. Although fully penetrant mutations in several genes have been identified and can explain the pathogenic mechanisms underlying a great portion of the Mendelian forms of the disease, still a significant number of families and sporadic cases remains genetically unsolved. We performed whole exome sequencing in 100 patients with a late-onset and heterogeneous FTD-like clinical phenotype from Apulia and screened mendelian dementia and neuronal ceroid lipofuscinosis genes. We identified a nonsense mutation in SORL1 VPS domain (p.R744X), in 2 siblings displaying AD with severe language problems and primary progressive aphasia and a near splice-site mutation in CLCN6 (p.S116P) segregating with an heterogeneous phenotype, ranging from behavioural FTD to FTD with memory onset and to the logopenic variant of primary progressive aphasia in one family. Moreover 2 sporadic cases with behavioural FTD carried heterozygous mutations in the CSF1R Tyrosin kinase flanking regions (p.E573K and p.R549H). By contrast, only a minority of patients carried pathogenic C9orf72 repeat expansions (1%) and likely moderately pathogenic variants in GRN (p.C105Y, p.C389fs and p.C139R) (3%). In concert with recent studies, our findings support a common pathogenic mechanisms between FTD and neuronal ceroid lipofuscinosis and suggests that neuronal ceroid lipofuscinosis genes should be investigated also in dementia patients with predominant frontal symptoms and language impairments.

Brain Structural Covariance Networks in Behavioral Variant of Frontotemporal Dementia.

Recent research on behavioral variant frontotemporal dementia (bvFTD) has shown that personality changes and executive dysfunctions are accompanied by a disease-specific anatomical pattern of cortical and subcortical atrophy. We investigated the structural topological network changes in patients with bvFTD in comparison to healthy controls. In particular, 25 bvFTD patients and 20 healthy controls underwent structural 3T MRI. Next, bilaterally averaged values of 34 cortical surface areas, 34 cortical thickness values, and six subcortical volumes were used to capture single-subject anatomical connectivity and investigate network organization using a graph theory approach. Relative to controls, bvFTD patients showed altered small-world properties and decreased global efficiency, suggesting a reduced ability to combine specialized information from distributed brain regions. At a local level, patients with bvFTD displayed lower values of local efficiency in the cortical thickness of the caudal and rostral middle frontal gyrus, rostral anterior cingulate, and precuneus, cuneus, and transverse temporal gyrus. A significant correlation was also found between the efficiency of caudal anterior cingulate thickness and Mini-Mental State Examination (MMSE) scores in bvFTD patients. Taken together, these findings confirm the selective disruption in structural brain networks of bvFTD patients, providing new insights on the association between cognitive decline and graph properties.

Plasma Inflammatory Cytokines Are Elevated in ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease which leads to death in a median time of 2-3 years. Inflammation has been claimed important to the ALS pathogenesis, but its role is still not well-characterized. In the present study, a panel of five cytokines (IL-2, IL-6, IL-10, IFN-gamma, and TNF-alpha) measured in plasma has been investigated in ALS. These biomarkers of inflammation were measured in a population-based cohort of 79 patients with ALS and 79 age- and sex-matched healthy controls using the Bio-Plex technology (Bio-Rad). All the five cytokines were significantly increased in plasma samples of patients compared with controls (p < 0.0001), with IL-6 having the highest median concentration (10.11 pg/ml) in the ALS group. Furthermore, IL-6 was the plasma cytokine with the highest discrimination ability between patients and controls according to the receiver operating characteristic analysis (area under the curve = 0.93). At a cut-off point of 5.71 pg/ml, it was able to classify patients and controls with 91% of sensitivity and 87% of specificity. In the ALS group, plasma IL-6 concentration correlated with demographic (age: rs = 0.25, p = 0.025) and clinical (revised ALS Functional Rating Scale at evaluation: rs = -0.32, p = 0.007; Manual Muscle Testing: rs = -0.33, p = 0.004; progression: rs = 0.29, p = 0.0395) parameters. In line with previous studies, our results confirm that inflammatory cytokines are elevated in ALS, supporting a possible role of inflammation in disease mechanism and progression. However, the precise role of inflammation in ALS needs to be further investigated on larger samples and with more mechanistic studies.

Telemedicine for Delivery of Care in Frontotemporal Lobar Degeneration During COVID-19 Pandemic: Results from Southern Italy.

BACKGROUND: The COVID-19 pandemic is changing clinical practice in neurology, after the governments decided the introduction of social distancing and interruption of medical non-emergency services in many countries. Teleneurology is an effective tool for the remote evaluation of patients but its adoption for frontotemporal lobar dementia (FTD) is in a preliminary stage. OBJECTIVE: We evaluated multidisciplinary assessment of patients with FTD using telehealth during the COVID-19 pandemic. METHODS: All patients received a diagnosis of FTD during 2018-2019 according to international criteria. A structured questionnaire and Clinical Dementia Rating Scale (CDR)-FTD were used by the neurologist with patients and/or caregivers. Index symptoms of COVID-19 infection were searched. RESULTS: Twenty-eight clinical interviews were completed with caregivers and four with both patients/caregivers. Most patients and caregivers were satisfied with the neurological interview and expressed their willingness to continue to be included in remote evaluation programs (90%). Fifty percent of patients experienced significant worsening of clinical picture and quality of life since the start of social distancing. The CDR-FTD scale revealed a significant worsening of behavior (p = 0.01) and language functions (p = 0.009), compared to the last in-person evaluation at the center. One patient presented index symptoms of COVID-19 infection and was confirmed to be positive for COVID-19 with pharyngeal swab. CONCLUSION: The study was conducted in Italy, one of the countries hit particularly hard by the COVID-19 pandemic, with interruption of all non-emergency medical services. Our study indicates that telemedicine is a valid tool to triage patients with FTD to increase practice outreach and efficiency.

Telemedicine is a useful tool to deliver care to patients with Amyotrophic Lateral Sclerosis during COVID-19 pandemic: results from Southern Italy.

BACKGROUND: Teleneurology is an effective tool for the rapid evaluation of patients in remote locations with a well-established use in stroke and epilepsy. To date its adoption for Amyotrophic Lateral Sclerosis (ALS) care is still in a preliminary stage. We evaluated the feasibility of multidisciplinary assessment of patients with ALS, using telememedicine during the emergency determined by the COVID-19 pandemic. Methods: All patients included in this survey had received a diagnosis of ALS according to international criteria after a complete clinical and paraclinical assessment during 2019. A structured questionnaire was used by the neurologist with the patient or the caregiver. A video interaction was offered but refused by all patients because they did not feel comfortable or did not have smartphone. Results: Out of 31 clinical interviews 8 were completed directly with the patients and 23 with patients' caregivers. In a successive survey, most of patients were satisfied with the neurological interview (85%), the possibility to interact directly with the clinician being at home (85%) and reduction of economic and time costs because they avoided unnecessary travel to the clinic. Most of subjects expressed their willingness to continue to be included in remote evaluation programs (90%). Notably, none of the patients presented index symptoms of Covid-19 infection. Conclusion: Our study indicates that telemedicine is a valid tool to triage patients with ALS to increase practice outreach and efficiency. Delivery of care via telemedicine was effective and successful in people with ALS in the dramatic and sudden crisis determined by Covid-19 outbreak.

Age-Related Central Auditory Processing Disorder, MCI, and Dementia in an Older Population of Southern Italy.

OBJECTIVE: We explored the associations of age-related central auditory processing disorder (CAPD) with mild cognitive impairment (MCI) and dementia in an older population-based cohort in Apulia, Southern Italy (GreatAGE Study). STUDY DESIGN: Cross-sectional data from a population-based study. SETTING: Castellana Grotte, Bari, Italy. SUBJECTS AND METHODS: Between 2013 and 2018, MCI, dementia, age-related CAPD (no disabling hearing loss and <50% score on the SSI-ICM test [Synthetic Sentence Identification-Ipsilateral Competing Message]), neurologic and neuropsychological examinations, and serum metabolic biomarkers assays were investigated on 1647 healthy volunteers aged >65 years. RESULTS: The prevalences of age-related CAPD, MCI, and dementia were 14.15%, 15.79%, and 3.58%, respectively. Among the subjects with MCI and dementia, 19.61% and 42.37% had age-related CAPD. In the regressive models, age-related CAPD was associated with MCI (odds ratio, 1.50; 95% CI, 1.01-2.21) and dementia (odds ratio, 2.23; 95% CI, 1.12-4.42). Global cognition scores were positively associated with increasing SSI-ICM scores in linear models. All models were adjusted for demographics and metabolic serum biomarkers. CONCLUSION: The tight association of age-related CAPD with MCI and dementia suggests the involvement of central auditory pathways in neurodegeneration, but it is not clear which is the real direction of this association. However, CAPD is a possible diagnostic marker of cognitive dysfunction in older patients.

The Italian Version of the Test Your Memory (TYM-I): A Tool to Detect Mild Cognitive Impairment in the Clinical Setting.

The Test Your Memory (TYM) is a brief self-administered, cognitive screening test, currently used in several settings. It requires minimal administrator supervision and the computation of the final test score takes approximately 2 min. We assessed the discrimination ability of the Italian version of the TYM (TYM-I) in detecting Mild Cognitive Impairment (MCI) in clinical setting. TYM-I was administered to 94 MCI patients and 134 healthy controls. The clinical diagnosis of MCI was considered as the gold standard. An extended formal neuropsychological test battery was used to define MCI subtypes. Receiver Operating Characteristic (ROC) analyses were conducted to find the optimal cut-off and measure discrimination ability of TYM-I in detecting MCI. TYM-I had a similar area under the curve (AUC = 0.85) point estimate as Mini Mental State Examination (MMSE) (AUC = 0.83). A TYM-I score lower or equal to 36 was found to be optimal cut off to detect MCI. The TYM-I showed the highest discrimination ability among individuals aged more than 70 and high educational level (AUC = 0.89). The amnestic MCI subtype patients, compared to non-amnestic MCI patients, had worse performance in recall, orientation and visuospatial abilities TYM-I subscores. The TYM-I is a valid screening test in detecting cognitive dysfunction, easily carried out in clinical practice. The TYM-I subscores may allow to identify amnestic and non-amnestic MCI subtypes.

The Age-Related Central Auditory Processing Disorder: Silent Impairment of the Cognitive Ear.

Age-related hearing loss (ARHL), also called presbycusis, is a progressive disorder affecting hearing functions and among the elderly has been recognized as the third most frequent condition. Among ARHL components, the age-related central auditory processing disorder (CAPD) refers to changes in the auditory network, negatively impacting auditory perception and/or the speech communication performance. The relationship between auditory-perception and speech communication difficulties in age-related CAPD is difficult to establish, mainly because many older subjects have concomitant peripheral ARHL and age-related cognitive changes. In the last two decades, the association between cognitive impairment and ARHL has received great attention. Peripheral ARHL has recently been defined as the modifiable risk factor with the greatest impact on the development of dementia. Even if very few studies have analyzed the relationship between cognitive decline and age-related CAPD, a strong association was highlighted. Therefore, age-related CAPD could be a specific process related to neurodegeneration. Since these two disorders can be concomitant, drawing causal inferences is difficult. The assumption that ARHL, particularly age-related CAPD, may increase the risk of cognitive impairment in the elderly remains unchallenged. This review aims to summarize the evidence of associations between age-related CAPD and cognitive disorders and to define the diagnostic procedure of CAPD in the elderly. Finally, we highlight the importance of tailoring the rehabilitation strategy to this relationship. Future longitudinal studies with larger sample sizes and the use of adequate assessment tools that can disentangle cognitive dysfunction from sensory impairments are warranted.

Early pathological gambling in co-occurrence with semantic variant primary progressive aphasia: a case report.

We have comprehensively documented a case of semantic variant of primary progressive aphasia (sv-PPA) presenting with early-onset pathological gambling (PG). While a growing number of studies have shown the presence of behavioral alterations in patients with sv-PPA, PG has been observed only in the behavioral variant of frontotemporal dementia (bv-FTD). To date, no case of PG with the co-occurrence of prominent semantic deficits at the onset of the disease has been reported in the literature. Impulse disorders at onset may wrongly lead to a misdiagnosis (ie, psychiatric disorders). Therefore, a wider characterization of cognitive/aphasia symptoms in patients presenting impulse disorders and predominant language dysfunctions is recommended.

Incidence of frontotemporal lobar degeneration in Italy: The Salento-Brescia Registry study.

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 patients' 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.

Promising therapies for the treatment of frontotemporal dementia clinical phenotypes: from symptomatic to disease-modifying drugs.

INTRODUCTION: Frontotemporal dementia (FTD) is a heterogeneous clinical entity that includes several disorders characterized by different cellular mechanisms. Distinctive clinical features in FTD include behavioral, affective, and cognitive symptoms. Unfortunately, little progress has been made over the past 20 years in terms of the development of effective disease-modifying drugs with the currently available symptomatic treatments having limited clinical utility. AREAS COVERED: This article reviews the principal pharmacological intervention studies for FTD. These are predominantly randomized clinical trials and include symptomatic treatments and potential disease-modifying drugs. EXPERT OPINION: There is insufficient evidence on effective treatments for FTD and studies with better methodological backgrounds are needed. Most studies reporting therapeutic benefits were conducted with selective serotonin reuptake inhibitors, while anti-dementia drugs have been ineffective in FTD. Since the underlying pathology of FTD mostly consists of abnormal tau protein or TDP-43 aggregates, treatments are being developed to interfere with their aggregation process or with the clearance of these proteins. Furthermore, disease-modifying treatments remain years away as demonstrated by the recent negative Phase III findings of a tau aggregation inhibitor (LMTM) for treating the behavioral variant of FTD. The results from current ongoing Phase I/II trials will hopefully give light to future treatment options.

Episodic memory and learning rates in amyotrophic lateral sclerosis without dementia.

In amyotrophic lateral sclerosis (ALS), memory deficits may be primary or secondary to executive dysfunction. We assessed episodic memory and executive function of nondemented ALS patients, comparing episodic memory profiles and learning rates of ALS patients with those of mild cognitive impairment (MCI) subjects and cognitively healthy controls (HC). In a multidisciplinary tertiary centre for motor neuron disease, 72 nondemented ALS patients, 57 amnestic MCI (aMCI), 89 single non amnestic MCI with compromised executive functions (dysexecutive MCI), and 190 HC were enrolled. They were screened using the Frontal Assessment Battery and Mini Mental State Examination. Episodic memory performances and learning rates were tested using the Rey Auditory Verbal Learning Test (RAVLT). Episodic memory dysfunction (immediate recall) was found in 14 ALS patients (19.4%). The ALS group had lower performance than HC on immediate recall, without differences in learning rate, and better performance than aMCI subjects on all RAVLT measures. Compared to dysexecutive MCI subjects, ALS patients had only better verbal learning abilities. ALS patients with executive dysfunction had a lower score on immediate and delayed recalls, verbal learning, and primacy effect than ALS patients without executive dysfunction. The immediate recall among couples of diagnostic groups differed in a statistically significant way except for the ALS/dysexecutive MCI groups. In ALS patients, episodic memory performances and learning rates appeared to be better than in aMCI subjects and similar to those with dysexecutive MCI, suggesting also a secondary functional damage due to executive impairment.

Comparative evaluation of two immunoassays for cerebrospinal fluid ß-Amyloid1-42 measurement.

AIM OF THE STUDY: Beta-Amyloid 1-42 peptide (ßA42) is a cerebro-spinal fluid (CSF) biomarker, key element of the NIA Alzheimer's disease diagnostic criteria. The enzyme-linked immunosorbent assay (ELISA) has been the mainstay method for ßA42 measurement on cerebrospinal fluid (CSF). Recently, a new ßA42 measurement method in chemiluminescence enzyme immunoassay (CLEIA) is available on Lumipulse G 600 II automatic platform. The aim of the work was to evaluate the concordance of the ELISA and the new method (CLEIA) in the CSF ßA42 levels measurement. MATERIALS AND METHODS: CSF ßA42 levels were assayed in 49 samples using the ELISA method (Innotest ß- amyloid 1-42, Fujirebio Europe N.V., Gent, Belgium) and CLEIA method on Lumipulse G600II fully automatic platform (Lumipulse G ß- amyloid 1-42, Fujirebio Europe N.V., Gent, Belgium). We compared values of the two methods using acceptability interval based on Inherent Combined Imprecision (ICI), the Passing-Bablok regression analysis, the Pearson correlation coefficient (r) and the Bland-Altman plot. RESULTS: The analysis of the ICI showed that the two methods differ substantially. The regression equation (y = -103.04 + 1.52×) highlighted the presence of proportional systematic difference, without significant deviation from linearity (p = .42). The Pearson correlation coefficient was 0.826. The Bland-Altman plot analysis showed a significant systematic difference in the two methods: ELISA measurements were in average -27.06% (95% CI -31.89 to -22.23%) lower compared to CLEIA ones. CONCLUSIONS: Our study highlighted a difference between the two methods. Therefore, the cut-off for the normal levels of ßA42 should be reviewed in the laboratory report.

Loss of Swallow Tail Sign on Susceptibility-Weighted Imaging in Dementia with Lewy Bodies.

We assessed nigral dorsolateral hyperintensity (swallow tail sign) at susceptibility-weighted imaging using 3T-MRI in 15 dementia with Lewy bodies (DLB), 11 Alzheimer's disease (AD), and 8 frontotemporal dementia (FTD) patients and 10 subjects with subjective memory complaint (SMC). More DLB patients lacked nigral hyperintesity (p < 0.05). Sensitivity, specificity, and accuracy of DLB diagnosis were, respectively: 80%, 64%, and 73% versus AD; 80%, 75%, and 78% versus FTD; and 80%, 90%, and 84% versus SMC. Considering bilateral loss, sensitivity decreased (53%) but specificity increased (82-100%). Swallow tail sign loss, especially if bilateral, can be useful for DLB diagnosis.

Social Dysfunction in Older Age and Relationships with Cognition, Depression, and Apathy: The GreatAGE Study.

BACKGROUND: Most studies focused on only one measure of social dysfunction in older age, without proper validation and distinction across different dimensions including subjectivity, structural, and functional aspects. OBJECTIVE: We sought to validate the Social Dysfunction Rating Scale (SDRS) and its factorial structure, also determining the association of SDRS with cognitive functions, global psychopathology, and social deprivation. METHODS: The SDRS was administered to 484 Italian community-dwelling elderly, recruited in the GreatAGE study, a population-based study on aging conducted in Castellana Grotte, Bari, Southern Italy. We determined objective and subjective psychometric properties of SDRS against the gold standard evaluation of social dysfunction according to the Semi-structured Clinical Diagnostic Interview for DSM-IV-TR Axis I Disorders (SCID-I) criterion. RESULTS: The SDRS showed a moderate accuracy with an optimal cut-off of 26 maximized with higher sensitivity (0.74,95% CI:0.63-0.84) than specificity (0.57,95% CI:0.50-0.64). A five-factor structure was carried out and five dimensions of SDRS were identified (loneliness; social isolation; feeling of contribution/uselessness; lack of leisure activities; anxiety for the health). Education and global cognitive functions were inversely correlated to SDRS, while a direct association with global psychopathology, depression, and apathy was found. The prevalence of higher SDRS scores was major in subjects with current psychiatric disorders versus other subjects.∥Conclusion: The SDRS could be a valid instrument to capture both size and quality of social dysfunction, both in subjects with psychiatric disorders and in normal subjects. Several categories of social dysfunction differed only in the degree of health deprivation, not in social or material deprivation.

Plasma ß-amyloid1-42 reference values in cognitively normal subjects.

BACKGROUND: In clinical practice, the use of plasma ß-Amyloid1-42 (Aß1-42) as biomarker for Alzheimer's disease is largely limited by the absence of reference values. The aim of this study was to evaluate Aß1-42 plasma concentrations in cognitively normal subjects and to propose reference values. METHODS: Plasma samples were obtained from 245 subjects, with a wide age-range (19-89 years), enrolled at the Unit of Laboratory Medicine of the "Azienda Ospedaliera Cardinale G. Panico" (younger subjects) and from a population-based study on aging (GreatAGE study) (older subjects). Three different age-groups were established: young (≤ 34), adult (35 ≤ age ≤ 64) and old (>64). The Innogenetics Elisa kit for plasma Aß1-42 was used for the analysis. RESULTS: The mean (SD) concentration of plasma Aß1-42 was 17.65 (5.71) pg/mL. A positive trend was found in Aß1-42 levels across the three age groups (p < .0001): young subjects showed values of Aß1-42 significantly lower than the adult group (p < .0001) and than the old one (p < .0001 overall); no significant differences were found between the adult and the old groups (p = 1.0000). For the entire cohort the lower limit of 90% Reference Interval, double-sided, was 8.12 pg/mL (95% CI 6.77-9.45) and the upper limit was 29.00 pg/mL (95% CI 27.01-31.00). CONCLUSION: The present study proposes reference values for plasma Aß1-42. Nevertheless, further studies are needed to confirm these results and corroborate the use of these reference values in clinical practice.