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In Parkinson’s disease (PD), physical activity may represent a possible non-pharmacological intervention not only for improving motor symptoms but also for modulating cognitive impairment. To evaluate the efficacy of an intensive physical program on cognitive functions in mid-stage PD patients with mild cognitive impairment (PD-MCI) over a 6-month follow-up. This is a 6-month randomized controlled follow-up study. 40 PD-MCI patients were randomized to receive physical therapy (PT) or no specific intervention beside drug treatment (CT). Cognitive and motor assessments were performed at baseline (T0), 4 weeks after baseline (T1) and 6 months after T0. In a previous study, we reported a significant improvement in global cognitive functioning and attention/working-memory at T1. Here, we evaluated the residual effect of the training intervention at 6 months on both cognitive and motor performances. Intra-group analysis showed that at T2 most of cognitive and motor performances remained stable in the PT when compared to T0, while a significant worsening was observed in the CT. Between-group comparison at T2 showed significantly better results in PT than CT as regards MoCA and motor scales. The percentage change of cognitive and motor performances between T1 and T2 confirmed the benefit of physical therapy on global cognitive functioning scores (MMSE and MoCA). In this follow-up extension of a longitudinal randomized controlled study, we demonstrated that physical therapy has a positive effect on cognitive functions, which extends beyond the duration of the treatment itself to, at least temporarily, reducing cognitive decline. Trial registration number (ClinicalTrials.gov): NCT04012086 (9th July 2019).

The effectiveness of computer-based cognitive training (CCT) remains controversial, especially in older adults with neurodegenerative diseases. To evaluate the efficacy of CCT in patients with Parkinson’s disease and mild cognitive impairment (PD-MCI). In this randomized controlled trial, 53 patients were randomized to receive CCT delivered by means of CoRe software, traditional paper-and-pencil cognitive training (PCT), or an unstructured activity intervention (CG). In each group, the intervention lasted 3 consecutive weeks (4 individual face-to-face sessions/week). Neuropsychological assessment was administered at baseline (T0) and post-intervention (T1). Outcome measures at T0 and T1 were compared within and between groups. The Montreal Overall Cognitive Assessment (MoCA) was taken as the primary outcome measure. Unlike the PCT group and the CG, the patients receiving CCT showed significant medium/large effect size improvements in MoCA performance, global cognition, executive functions, and attention/processing speed. No baseline individual/demographic variables were associated with greater gains from the intervention, although a negative correlation with baseline MoCA performance was found. CCT proved effective in PD-MCI patients when compared with traditional PCT. Further follow-up assessments are being conducted to verify the retention of the gains and the potential ability of the tool to delay conversion to PD-dementia. Trial registration number (ClinicalTrials.gov): NCT04111640 (30th September 2019).

BackgroundBehavioral and psychological symptoms of dementia (BPSD) have a high prevalence, and their presence is associated with a severe impact in terms of social costs. However, dedicated clinical tools or biomarkers to detect these symptoms are lacking. Thus, BPSD management in clinical settings is challenging. The aim of this study was to investigate the perception and the treatment strategies for BPSD in Italian centers working in the dementia field.MethodsA multicenter, national survey was developed by BPSD Study Group of the Italian Neurological Society for Dementia (SINDEM). The survey consisted of a semi-structured questionnaire that was e-mailed to SINDEM members, dementia centers part of the national network of memory clinics (Centers for Cognitive Deterioration and Dementia [CDCD]), and clinicians working in dementia care settings. The questions were focused on (1) perceived global frequency and relevance of BPSD; (2) tools used to assess BPSD; (3) pharmacological treatment for psychosis, apathy, agitation, aggression, depression, anxiety, sleep, and nutrition disturbances; (4) non-pharmacological treatments; (5) drugs side effects.ResultsOne-hundred and thirty-six clinicians participated in this study. Seventy-nine participants worked in a CDCD and 57 in other settings. The perceived frequency of BPSD was 74%. BPSD are detected by means of a clinical assessment for 96.3% or a caregiver interview for 97%. For psychosis treatment the first choice was atypical antipsychotics (83.3%), followed by typical antipsychotic (8.9%) and antidepressants (4.8%). For agitation, atypical antipsychotics were the first-choice treatment in 64% of cases and antidepressants in 16.1%. For aggression, the most used drugs were atypical antipsychotics (82.9%). For anxiety, 55.2% use antidepressants, 17.9% use atypical antipsychotics, and 16.9% use benzodiazepines. Interestingly, most of the centers apply non-pharmacological treatments for BPSD. Some differences emerged comparing the responses from CDCD and other care settings.ConclusionThe survey results revealed many differences in BPSD perception, treatment options, and observed side effect according to the clinical setting. This variability can be explained by the absence of clear guidelines, by differences in patients' characteristics, and by clinical practice based on subjective experience. These results suggest that producing guidelines for the pharmacological treatment of BPSD is a major need.

Background Circadian dysfunction is thought to take part in the pathogenesis of sleep disorders in Alzheimer's disease (AD) and in AD pathophysiology itself. Objective Our study aims to calculate dim light melatonin onset (DLMO) secretion in order to define the circadian phase in patients with AD at an early stage of the disease. Methods Twenty-one patients (M/F: 11/10; mean age 74.1 ± 5.4 years; mean disease duration 3.4 ± 1.6 years) with a diagnosis of AD and 17 healthy controls (HC; M/F: 10/7; mean age 67.47 ± 3.8 years) were investigated for subjective nocturnal sleep quality and chronotype, for DLMO and quantitative aspects of the evening melatonin secretion by means of a 5-point in-home evening melatonin saliva test. Results Subjective sleep quality score on the Pittsburgh Sleep Quality Index questionnaire (PSQI) above 5 (p = 0.24), insomnia frequency as measured by Sleep Condition Indicator Questionnaire (p = 0.823) and the subjective chronotype according to Morning Evening Questionnaire (MEQ) scores distribution (p = 0.464) did not differ between AD and HC. However, DLMO occurred significantly later (55 min; p = 0.028), and melatonin secretion following DLMO was significantly decreased in AD patients compared to HC. Conclusion Initial evening secretion of melatonin proves to be delayed and mildly impaired in patients with a mild/moderate form of Alzheimer disease while patients' subjective sleep parameters and chronotype are reported to be similar to those of HC. These results indicate that subclinical altered patterns of melatonin secretion occur in subjects with AD at an early stage of the disease.

Background There is no successful pharmacological treatment for cognitive impairment in Parkinson's Disease, therefore treatments capable of slowing down the progression of cognitive dysfunction are needed. Objective To evaluate the effectiveness of a cognitive training, supported by the CoRe computerized tool, in patients with Parkinson's Disease Mild Cognitive Impairment. Methods This is a prospective, open-unblinded, randomized, controlled study. After baseline cognitive assessment (T0), enrolled patients were randomized to receive motor rehabilitation plus cognitive intervention (G1) or motor rehabilitation only (G2). Follow-up assessments were scheduled 4 weeks (T1) and 6 months after (T2). Global cognitive functioning scores (MOCA and MMSE) were considered as primary outcome. Outcome measures at T0, T1 and T2 were compared within- and between-groups. A percentage change score between T0 and next assessments was calculated to identify patients who improved, remain stable or worsened. Results Differently from G2, G1 showed a medium/large effect size improvement in primary (MoCA) and secondary outcome, both between T0 and T1 and T0 and T2. Moreover, within G1, most patients improved their cognitive state compared to the baseline. Conclusions Patients trained with CoRe showed a better evolution of cognitive decline, while untreated patients tended to get worse over time.

In the past, little or no attention was paid to cognitive disorders associated with depression (a condition sometimes termed pseudodementia). However, recent years have seen a growing interest in these changes, not only because of their high frequency in acute-stage depression, but also because they have been found to persist, as residual symptoms (in addition to affective and psychomotor ones), in many patients who respond well to antidepressant treatment. These cognitive symptoms seem to impact significantly not only on patients' functioning and quality of life, but also on the risk of recurrence of depression. Therefore, over the past decade, pharmacological research in this field has focused on the development of new agents able to counteract not only depressive symptoms, but also cognitive and functional ones. In this context, novel antidepressants with multimodal activity have emerged. This review considers the different issues, in terms of disease evolution, raised by the presence of cognitive disorders associated with depression and considers, particularly from the neurologist's perspective, the ways in which the clinical approach to cognitive symptoms, and their interpretation to diagnostic and therapeutic ends, have changed in recent years. Finally, after outlining the pharmacodynamics and pharmacokinetics of the first multimodal antidepressant, vortioxetine, it reports the main results obtained with the drug in depressed patients, also in consideration of the ever-increasing evidence on its different mechanisms of action in animal models.

The prevalence of neurodegenerative diseases is expected to increase over the next years, therefore, new methods able to prevent and delay cognitive decline are needed. To evaluate the effectiveness of a combined treatment protocol associating a computerized cognitive training (CoRe) with anodal transcranial direct current stimulation (tDCS). In this randomized controlled trial, 33 patients in the early stage of cognitive impairment were assigned to the experimental group (CoRE + real tDCS) or control group (CoRE + sham tDCS). In each group, the intervention lasted 3 consecutive weeks (4 sessions/week). A neuropsychological assessment was administered at baseline (T0), post-intervention (T1) and 6-months later (T2). The CoRE + real tDCS group only improved in working memory and attention/processing speed at both T1 and T2. It reported a stable MMSE score at T2, while the CoRE + sham tDCS group worsened. Age, mood, and T0 MMSE score resulted to play a role in predicting treatment effects. Combined multi-domain interventions may contribute to preventing or delaying disease progression. Trial registration number (ClinicalTrials.gov): NCT04118686

The use of biomarkers has recently supported the association between Alzheimer disease (AD) pathology and the logopenic variant of primary progressive aphasia (PPA). We aim to investigate possible differences in cerebrospinal fluid (CSF) biomarker concentrations in the three PPA variants, and to assess any agreement between CSF biomarkers and (18)F-florbetapir PET. A group of 10 PPA were retrospectively enrolled. Patients with logopenic variant (lvPPA) showed different levels of Aβ1-42 and p-tau compared to nonfluent/agrammatic and semantic variants (nfv/svPPA). All nfv/svPPA patients had negative amyloid PET. Among the lvPPA group, a negative amyloid PET was found only in one patient, who was also the only one to display a normal CSF. Thus, this small cohort appeared to display an excellent agreement between CSF and (18)F-florbetapir PET and suggest that these examinations may have the same validity in detecting in vivo evidence of AD pathology in PPA clinical variants.

Background: Circadian and sleep disturbances are associated with increased risk of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Wearable activity trackers could provide a new approach in diagnosis and prevention. Objective: To evaluate sleep and circadian rhythm parameters, through wearable activity trackers, in MCI and AD patients as compared to controls, focusing on sex dissimilarities. Methods: Based on minute level data from consumer wearable devices, we analyzed actigraphic sleep parameters by applying an electromedical type I registered algorithm, and the corresponding circadian variables in 158 subjects: 86 females and 72 males (42 AD, 28 MCI, and 88 controls). Moreover, we used a confusion-matrix chart method to assess accuracy, precision, sensitivity, and specificity of two decision-tree models based on actigraphic data in predicting disease or health status. Results: Wake after sleep onset (WASO) was higher (p

Background Sleep disorders and cognitive impairment are frequently reported in Parkinson's disease (PD) as non-motor disabling symptoms. While it is known that REM sleep Behaviour Disorder (RBD) in PD is associated with motor and cognitive decline, little is known about the neurobiological significance of NREM sleep arousal-related disorders. Objectives: to evaluate the cognitive and clinical correlates of arousal-related disorders in PD. Methods Clinical data and video-polysomnography were analysed from one hundred-seventy consecutive subjects with PD. Based on the neuropsychological assessment, the subjects were divided into three groups: no cognitive impairment (PD; n = 58), mild cognitive impairment (PD-MCI; n = 58) and overt dementia (PDD; n = 54). Results Arousal-related disorders by history were reported in 32.9% of the subjects: 10.3% PD, 31.6% PD-MCI and 59.3% PDD (p = 0.001). Video-PSG captured arousal-related disorders in 1.7% PD, 21.2% MCI-PD and 35.6% PDD (p = 0.001). Arousal-related disorders and RBD were recorded in the same night in 7.7% PD, 9.8% MCI-PD and 15.6% PDD (p = 0.04). Patients with arousal-related disorders captured at V-PSG have a longer disease duration (p = 0.003), higher UPDRS score (p = 0.039), longer duration of treatment with levodopa (p = 0.017) and dopamine agonists (p = 0.018), worse H&Y staging (p = 0.001), lower MMSE score (p = 0.019) and more frequently hallucinations (p = 0.004). In multivariate analysis, cognitive impairment significantly increases the risk of arousal-related disorders (OR 3.387–95% CI 1.395–8.220, p = 0.007). Conclusion Arousal-related disorders appear to be a marker of cognitive decline in PD. Recognizing arousal-related disorders should make clinicians aware of a possible cognitive decline in PD and eventually modify the therapeutic approach.

One thousand and 679 Alzheimer's Disease patients (early onset EO: 152 and late onset LO: 1527) were evaluated after 12, 36 and 60 months. At baseline EO patients have higher Mini Mental State examination (MMSE) and fewer comorbidities in respect to LO group. The MMSE score did not significantly differ after 12, 36 and 60 months; a more marked worsening in instrumental daily activities was observed after 36 months in the EO compared with the LO group. These data allow to conclude that EO patients may have a slight faster progression in the disease within the first 3 years after the diagnosis, but in a longer follow-up no differences exist in respect to LO group. The literature failed to identify specific factors capable to influence the disease progression in AD. Our data are in substantial agreement with the literature and seem to confirm the great heterogeneity of AD patients.

BackgroundFrontotemporal Spectrum Disorder (FTSD) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases often considered as a continuum from clinical, epidemiologic and genetic perspectives. We used localized brain volume alterations to evaluate common and specific features of FTSD, FTSD-ALS and ALS patients to further understand this clinical continuum.MethodsWe used voxel-based morphometry on structural MRI images to localize volume alterations in group comparisons: patients (20 FTSD, seven FTSD-ALS, 18 ALS) versus healthy controls (39 CTR), and patient groups between themselves. We used mean whole-brain cortical thickness to assess whether its correlations with local brain volume could propose mechanistic explanations of the heterogeneous clinical presentations. We also assessed whether volume reduction can explain cognitive impairment, measured with frontal assessment battery, verbal fluency and semantic fluency.ResultsCommon (mainly frontal) and specific areas with reduced volume were detected between FTSD, FTSD-ALS and ALS patients, confirming suggestions of a clinical continuum, while at the same time defining morphological specificities for each clinical group (e.g. a difference of cerebral and cerebellar involvement between FTSD and ALS). values suggested extensive network disruption in the pathological process, with indications of a correlation between cerebral and cerebellar volumes and in ALS. The analysis of the neuropsychological scores indeed pointed towards an important role for the cerebellum, along with fronto-temporal areas, in explaining impairment of executive and linguistic functions.ConclusionsWe identified common elements that explain the FTSD-ALS clinical continuum, while also identifying specificities of each group, partially explained by different cerebral and cerebellar involvement.

CoRe is a system for cognitive rehabilitation that has been successfully used for several years in hospital settings. Leveraging on the positive survey results from the potential final users (patients and their home caregivers), we developed HomeCoRe. This new version of the system will allow discharged patients to continue the rehabilitation treatment at home.

Study Objectives To search for a specific neuropsychological profile in idiopathic REM sleep behavior disorder (iRBD), able to predict the onset of neurodegenerative disorders. Methods In a longitudinal follow-up study of 63 consecutive iRBD patients (follow-up duration 6.7 ± 3.8 years), the baseline cognitive profile of converters to neurodegenerative disease was compared with that of the nonconverters. Five cognitive domains were assessed: memory, attention-working memory, executive functions, visuospatial abilities, language. Mild cognitive impairment (MCI) was diagnosed according to the Movement Disorder Society’s diagnostic criteria for Parkinson’s disease. Results 30 subjects (47.6%) developed a neurodegenerative disease (latency to conversion 60.33 ± 44.81 months). MCI was found in 50% of the converters and 12% of the nonconverters (p = .001), and its presence conferred a neurodegenerative disease risk of 10% at 3 years, 36% at 5 years, and 73% at 10 years (p = .002). Pathological equivalent scores on at least one neuropsychological test were detected in 46.7% of the converters versus 21.2% of the nonconverters in the memory domain (p = .032), in 40.0% versus 6.1% in that of executive functions (p = .002), and in 20.0% versus 3% in the visuospatial abilities domain (p = .047). On multivariate analysis, impaired executive functions significantly correlated with phenoconversion (p = .018). Lower Mini Mental State Examination (MMSE) scores (p = .004) and memory deficits (p = .031) were found in patients who developed dementia first. Conclusions Cognitive profile is useful for stratifying risk of phenoconversion in patients with iRBD. The presence of MCI and impaired executive functions, memory, and visuospatial abilities discriminated the converters. Lower MMSE scores and memory deficits may characterize those subjects who first develop dementia.

In the central nervous system Hsp70s seems to have a protective role in repair and removal of cellular proteins damaged by stress conditions. A protective role of Hsp70 was also shown in Alzheimer Disease. The HSP70-1 +190 G/C polymorphism is located in the gene 5'UTR region and it is implicated in alteration of the transcription binding factor; HSP70-2 +1267 A/G causes a silent mutation in the coding region and it seems to influence the mechanism of mRNA translation; HSP70-hom +2437 A/G causes a substitution Met → The (M493T) in the coding region and it seems to influence the bond with the substrate and therefore on the chaperone activity of hsp70. The aim of our study will be to investigate Alzheimer susceptibility to Hsp70 polymorphisms, taking into account our previous findings on HLA class III region, and to hypothesize a role of HLA class III haplotype configuration based on the variants of three genes: RAGE, HSP70 and TNF. We studied these polymorphisms with PCR-RFLP and PCR-TSP. We investigated 173 AD patients and 211 control subjects. Our results have shown a statistically significant decrease of the C allele frequency of the HSP70-1 +190 G/C polymorphism in AD patients vs controls (P value = 0,018), as well as the G allele of HSP70-2 +1267 G/A (p value = 0,02). We focalized our attention on haplotype reconstruction. We have observed a significant statistically decrease of GGT haplotype frequency (empirical p-value=0.0133 ); GAT haplotype was statistically significant increase in AD patients compared with control (empirical p-value=0.007). The total HLA class III haplotype are reconstructed. The causative haplotypes are the following ones: TTGATGGG ( p value =0,005; empirical p =0,0042); TTGATAGG (p value =0,45; empirical p =0,034). Patients with these haplotypes may show an earlier onset of the disease than patients with TTGGTGGG (p value=0,0138; empirical p =0,0102); TTCGTGGG (p value=0,021; empirical p =0,017); TTCGTGGA (p value =0,058; empirical p =0,043) haplotypes. The overall variation of the haplotypes formed by the RAGE and TNF and HSP70 variants influenced the presence of the AD phenotype (omnibus association LR test p-value 0.00185), HSP701 and HSP702 showed independent effect on AD risk after adjusting for the effect of the entire haplotype (conditional LR test p-value=0.0114 and p-value=0.0044 respectively). These data confirm the involvement of HLA class III in AD.

BACKGROUND AND PURPOSE The clinical differentiation between parkinsonism in idiopathic normal pressure hydrocephalus (iNPH) and Parkinson's disease (PD) remains challenging in the initial phase. Whether an early cognitive profiling might support the differential diagnosis of early iNPH and PD was addressed. METHODS Neuropsychological tests of 40 iNPH subjects with early symptoms resembling parkinsonism were retrospectively evaluated together with 47 de novoPD patients (dnPD). Only neuropsychological tests performed within 1 year from the first motor symptom were included. The cognitive spectrum of iNPH and dnPD was also compared with a sample of 70 normal controls. RESULTS A clear difference in the cognitive profile of iNPH, dnPD patients and normal controls was shown. 65% of iNPH subjects showed a diffuse cognitive impairment, including memory, visuospatial abilities, fronto-executive functioning and attention, whereas only 25.5% of the dnPD patients presented an executive dysfunction. 35% of iNPH and 74.5% of PD patients performed within the normal range (P < 0.05). CONCLUSION Subjects with iNPH showed an early and diffuse alteration of cognition with respect to dnPD patients. Performing a prompt and accurate neuropsychological evaluation might support the differential diagnosis of these two conditions of parkinsonism.

Objectives This paper describes the results of a randomized clinical trial about the effectiveness of a computerized rehabilitation treatment on a sample of 31 patients affected by Parkinson disease. Methods Computerized exercises were administered by the therapists to the intervention group (n = 17) through the CoRe tool, which automatically generates a big variety of exercises leveraging on a stimuli set (words, sounds and images) organized into a dedicated ontology. A battery of standard neuropsychological tests was performed for patients' assessment at baseline, after the treatment (that lasted 1 month), and after 6 months from the treatment stop. The control group underwent a sham intervention. Results Results show a statistically significant clinical benefit from computerized rehabilitation with respect to sham treatment. For the intervention group, response time and response accuracy were integrated into a weighted score that accounts also for the specific cognitive burden of each exercise. Differently from the control group, the majority of patients in the intervention group showed an improvement in that score, more marked in the first week of treatment, and which lasts for the entire treatment period, which could account both for a quick learning effect and for an improvement of cognitive conditions. Good usability of CoRe, already observed in previous studies, was confirmed by the present trial, where the percentage of protocol completion in the intervention group is very high (all but one patient are above 90%). Conclusions The CoRe system showed to be effective to improve some cognitive abilities in patients with Parkinson disease. However, after the end of the training, the benefit is hardly maintained over time. These findings support the implementation of CoRe in the clinical routine and the continuation of the treatment after discharge through the use of a homecare version of the system.

The Alzheimer’s disease “inflammation hypothesis” has emerged only recently, suggesting the risk of developing AD might be influenced by variants of genes encoding for inflammatory mediators. In order to investigate in this direction, genomic DNA from 194 Italian AD cases and 454 healthy controls matched by gender and ethnicity was analyzed for the Receptor for Advanced Glycation End products (RAGE, HLA class III-centromere portion) -374 and - 429 SNPs and for the Tumor Necrosis Factor-alpha (TNF-α, HLA class III-telomere portion) -857, -308 and -238 SNPs by RFLP and Real Time PCR. Our data show statistically significant deviations between AD patients and healthy controls concerning RAGE -374 SNP genotype (TT: p=0.0084) and allele (T, A: p=0.0081) frequencies; TNF-α -308 SNP AA genotype (p=0.0433) and TNF-α -238 SNP genotype (GG: p=0.0138) and allele (G, A: p=0.0151) frequencies. Furthermore, significant differences between the study groups and regarding RAGE TC (p=0.05) and AC (p=0.009) haplotypes are present, while TNF-α haplotype reconstruction point out a statistically significant difference between patients and controls regarding AGG haplotype (p=0.002). Finally, from the combination of the individually significant SNPs of the two genes (RAGE -374, TNF-α -238 and -308) we performed an HLA class III haplotype reconstruction finding significant differences between AD subjects and controls regarding the TAG (p=0.019) and TGA (p=0.008) haplotypes. The implication of these haplotypes with the disease points to a possible involvement of entire HLA class III region in AD susceptibility.

Study objectives To investigate the capacity of neuropsychological deficits in idiopathic rapid eye movement sleep behavior disorder (iRBD) to predict the development of dementia and/or parkinsonism. Design Prospective longitudinal follow-up study. Setting Tertiary sleep center. Patients Twenty patients with initial iRBD (19 males, mean age 66.1 ± 7.1) underwent a clinical and neuropsychological follow-up within a mean of 43 ± 19 months. Neuropsychological performances at baseline were compared with those of healthy controls matched for sex, age, and education. Interventions Discontinuation of clonazepam at least 7 days before the follow-up evaluation. Results At follow-up, the Wilcoxon test showed a significant worsening of scores on Raven Colored Matrices 47 (P = 0.01), Attentive matrices (P = 0.002), phonemic (P = 0.04) and sematic (P = 0.04) fluency. Thirteen patients (65%) showed cognitive deterioration involving multiple domains. Of these, four patients (20%) maintained a stable cognitive dysfunction and nine (45%) showed a progression of cognitive dysfunction: six (30%) in constructional abilities (P = 0.03), four (20%) in short-term memory (P = NS), three (15%) in executive functions and non-verbal logic (P = NS), one (5%) in verbal fluency (P = NS), and one (5%) in long-term memory (P = NS) (McNemar test). Seven patients (35%) retained a normal cognitive profile. Mild cognitive impairment (MCI) was diagnosed at baseline in seven patients (35%). At follow-up, three of these patients showed overt dementia that was accompanied by parkinsonism in all cases; one had worsened from non-amnesic single-domain to nonamnesic multiple-domain MCI, two were stable, and one patient no longer met the criteria for MCI. Four patients (20%) without MCI at baseline had MCI at follow-up. Patients who developed MCI/dementia had an older age at disease onset (65.8 ± 5.4 versus 56.8 ± 9.3; P = 0.01) compared with those who did not. Conclusions Our findings corroborate evidence that visuospatial abilities constitute the area most affected in idiopathic rapid eye movement sleep behavior disorder (learning as a stable deficit and copying as an evolving deficit). Cognitive deterioration, involving mainly nonverbal logic, attention, and executive functions, can be observed in rapid eye movement sleep behavior disorder follow-up, suggesting an underlying evolving degenerative process. Our data confirm that mild cognitive impairment is frequent in idiopathic rapid eye movement sleep behavior disorder. The presence of mild cognitive impairment predicts the eventual risk of developing dementia, which seemed to be associated with parkinsonism.

Knowledge of sleep architecture and disorders of nocturnal sleep in dementia with Lewy bodies (DLB) is limited by a lack of systematic video-polysomnographic (video-PSG) investigations. We describe video-PSG findings in 29 consecutive subjects diagnosed with DLB. All the patients underwent a clinical interview and overnight video-PSG monitoring. Twenty-nine nondemented patients with Parkinson's disease (PD) matched for age and sex with the DLB cases were selected for comparison. The DLB subjects showed less 1NREM sleep (P = .000) and more 2NREM sleep (P = .000) than the PD subjects. Sleep apnea (30.7% vs. 34.8%) and periodic limb movements (60.9% versus 50.0%) were frequent in both groups. Disruptive motor behavioral manifestations were more frequent in subjects with DLB (69.6% vs. 26.9%, P = .008) and consisted of not only REM sleep behavior disorder (RBD) but also confusional events (30.3% vs. 3.8%, P = .020) and arousal-related episodes mimicking RBD. Subjects with DLB in whom a sleep disturbance had been the presenting symptom performed better than those with other onset symptoms on both the Mini-Mental State Examination (22.2 ± 4.1 vs. 18.1 ± 4.6, P = .019) and the Frontal Assessment Battery (15.8 vs. 10.3, P = .010). Polysomnographic findings in DLB show a complex mix of overlapping sleep alterations: impaired sleep structure, sleep comorbidities, and various motor-behavioral events (not restricted to RBD). Clinicians should be aware of the possibility of misleading symptoms and of the risk of overlooking sleep comorbidities, and consider performing polysomnographic sleep investigations in selected cases. We found evidence that a sleep disturbance as the presenting symptom might indicate a different phenotype of the disease, characterized by milder cognitive impairment.

The relationship between cognitive and functional impairment in Alzheimer Disease (AD) at the earliest stages of the disease is not well characterized. This study aimed at investigating such relationships along AD evolution by means of the Disability Assessment for Dementia (DAD). Consecutive pairs of AD outpatients and their primary informal caregivers were enrolled. Patients were evaluated by means of the Mini Mental State Examination and neuropsychological tests. A clinician completed the Clinical Dementia Rating Scale to stage dementia severity and interviewed the caregivers to complete the Neuropsychiatric Inventory to assess behavioral disturbances and the DAD to evaluate patients’ functional competence. A total of 158 dyads were enrolled; the Mini Mental State Examination score was used to stratify patients into 4 groups (>24; 20 to 23.9; 10 to 19.9

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by ventricular dilation accompanied by a progressive triad of a gait disturbance, "dementia" and incontinence. We retrospectively evaluated cognitive profile, and its relationship with disease variables, in 64 iNPH patients. The iNPH group performed significantly worse than the control group on all neuropsychological tests, except for verbal memory (within the normal range). The patients were subdivided into four groups: group 1 (42%: global cognitive impairment); group 2 (24%: frontosubcortical dysfunction); group 3 (17%: isolated deficit of a single cognitive domain); group 4 (17%: no cognitive impairment). Group 1 was older, with a significantly longer disease duration and more severe motor disease, while groups 3 and 4 were younger and presented milder motor impairment and a shorter disease duration. These data suggest parallel progression of cognitive and motor impairment in iNPH; early shunt surgery might prevent the development, in older age, of dementia in these patients.

COMT (Catechol-O methyltransferase) gene is one of the key players in synaptic plasticity and in learning and memory mechanisms. A single nucleotide polymorphism (rs4680; G to A) in the COMT coding region causes Val158Met aminoacid substitution in the corresponding protein, with Val allele exhibiting a 3- to 4-fold increase in enzyme activity compared to Met. With the purpose of examining the influence of COMT as a genetic risk factor for cognitive impairment, we analyzed a sample of 248 healthy subjects, 276 patients affected by Alzheimer's disease (AD), and 70 subjects with mild cognitive impairment (MCI), the latter condition possibly representing a prodrome for dementia. All subjects were analyzed for COMT rs4680 polymorphism and APOE genotype. Our study strengthens data showing that APOE ε4 allele is an independent risk factor for AD and also a risk factor for MCI. Neither COMT alleles nor genotypes proved to be independently associated with the risk of AD or MCI in our sample. However, we found an association between COMT GG genotype (Val/Val) and APOE ε4 carrier status and the risk of AD and MCI. In particular, when GG genotype is included into the multinomial analysis, the risk of AD and MCI due to APOE ε4 allele is increased of about 2-3 fold; moreover, the risk conferred by the combination of G and ε4 alleles is more pronounced in male patients. To our knowledge, this synergistic effect is here shown for the first time on a population sample representative of Caucasian patients.

Background and aims: Memantine is an uncompetitive N-methyl-D-aspartate receptor antagonist. Clinical and observational studies have demonstrated its efficacy on both cognitive and behavioral symptoms of moderate-to-severe Alzheimer’s disease (AD) and described its good safety and tolerability profile. We report here our experience with memantine in patients with AD during a two-year follow-up. Methods: From June 2005 to May 2010, memantine was given to 201 outpatients with moderate-to-severe AD: 93 patients were concomitantly receiving treatment with acetyl cholinesterase inhibitors (AChEIs) (Group 1) and the other 108 were prescribed memantine as monotherapy (Group 2). All patients were administered the following scales: Mini Mental State Examination, Activities of Daily Living, Instrumental Activities of Daily Living, Neuropsychiatric Inventory. We report the results of followup assessments conducted at six months and 1, 2 and 3 years. Results: Sixteen patients (8%) stopped treatment within the first month because of side-effects. In each group, about 20% of subjects showed no deterioration at six months and 1 year, and this proportion decreased only slightly at 2 years. Higher NPI scores at baseline and psychotropic drug use emerged as factors significantly related to reduced response to treatment (p

This study was set out to describe caregiver-perceived burden and coping in early-stage Alzheimer disease (AD). A total of 163 consecutive pairs of patients with AD and their principal caregivers were initially recruited. The caregivers completed the Caregiver Burden Inventory (CBI) and the Coping Orientations to Problems Experienced scale, and also provided sociodemographic information; the patients with AD were assessed by means of the Mini Mental State Examination and the Neuropsychiatric Inventory. Data from 126 patient-caregiver pairs were analyzed. The caregivers (mean age 56.11±12.37 y) were mainly women (76%); 64% were the patient's offspring; 39% lived with the patient. From the CBI data, it emerged that caregivers perceived loss of personal time (objective burden, 33%) and the feeling of missing out on opportunities (developmental burden, 25%) as their main stressors. Total CBI score was negatively correlated with Mini Mental State Examination (P=0.005). As regards coping strategies, the caregivers predominantly used problem-oriented strategies associated with a positive attitude. The use of dysfunctional strategies was predictive of caregiver burden. It is important to be aware that avoidance and dysfunctional coping strategies predispose caregivers of patients with AD to higher level of distress, whereas successful caregiving seems to be based on the use of problem-oriented strategies early in the disease when solutions are still available.

We report an update of our previous observations in Alzheimer’s disease (AD) patients in the routine clinical practice considering in particular the interactions between age, concomitant pathologies, and treatment adherence. 2379 AD patients (M/F: 1058/1321, mean age: 74.1 ± 8.8) referred for a first visit to our center from September 2000 to April 2017. An increase of percentage of patients aged over 80 years along the years was confirmed (27% between September 2000 and December 2010, and 39% between January 2011 to April 2017). The patients over 80 years presented a Cumulative Illness Rating Scale (CIRS) significantly higher than patients under 80 years (p

Alien hand syndrome is a rare neurological disorder characterized by involuntary and uncontrollable motor behaviour, usually of an arm or hand. The patient perceives the affected limb as alien, and may personify it. The case of a 61-year-old right-handed woman who developed right posterior AHS after ischaemic stroke in the left posterior cerebral artery territory is reported. Neuroimaging studies disclosed no frontal or parietal involvement, while a posterior thalamic lesion was detected. A possible role of the thalamus in the genesis of AHS is discussed.

Aim of the study was to assess the added diagnostic value of neuropsychologic tests and structural neuroimaging (computed tomography or magnetic resonance) in the routine clinical assessment of demented patients in Italian expert centers. Nine centers were involved, located across the whole country (3 in Northern, 3 in Central, and 3 in Southern Italy). Diagnostic pathways were tracked for 474 patients with an expert diagnosis of neurodegenerative or vascular dementia (age 76+/-8; 62% females; Mini-Mental State Examination 17.70+/-5.7). The contribution of neuropsychology and structural neuroimaging to diagnosis was estimated as "number needed to test" (NNT), denoting the number of patients who need to undergo such procedures to improve expert diagnosis of 1 unit. Expert physicians reached their diagnosis without resorting to structural imaging examinations and neuropsychologic tests in 93% of Alzheimer disease (AD) and 76% of non-AD dementias. The completion of the extended assessment led to improvement of diagnostic accuracy in both cases: the NNT was 15.3 (95% confidence interval: 10.4-29.1) and 4.1 (3.0 to 6.5) for AD and non-AD diagnoses. The added value of structural imaging and neuropsychologic testing in the routine clinical assessment of demented patients is substantial in both AD and non-AD cases.