A double-blind randomized controlled trial combining cognitive training (CoRe) and neurostimulation (tDCS) in the early stages of cognitive impairment.

BACKGROUND: 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. AIMS: To evaluate the effectiveness of a combined treatment protocol associating a computerized cognitive training (CoRe) with anodal transcranial direct current stimulation (tDCS). METHODS: 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). RESULTS: 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. CONCLUSION: Combined multi-domain interventions may contribute to preventing or delaying disease progression. TRIAL REGISTRATION: Trial registration number (ClinicalTrials.gov): NCT04118686.

Evaluation of the efficacy of physical therapy on cognitive decline at 6-month follow-up in Parkinson disease patients with mild cognitive impairment: a randomized controlled trial.

BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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: Trial registration number (ClinicalTrials.gov): NCT04012086 (9th July 2019).

The Smart Aging Platform for Assessing Early Phases of Cognitive Impairment in Patients With Neurodegenerative Diseases.

Background: Smart Aging is a serious game (SG) platform that generates a 3D virtual reality environment in which users perform a set of screening tasks designed to allow evaluation of global cognition. Each task replicates activities of daily living performed in a familiar environment. The main goal of the present study was to ascertain whether Smart Aging could differentiate between different types and levels of cognitive impairment in patients with neurodegenerative disease. Methods: Ninety-one subjects (mean age = 70.29 ± 7.70 years)-healthy older adults (HCs, n = 23), patients with single-domain amnesic mild cognitive impairment (aMCI, n = 23), patients with single-domain executive Parkinson's disease MCI (PD-MCI, n = 20), and patients with mild Alzheimer's disease (mild AD, n = 25)-were enrolled in the study. All participants underwent cognitive evaluations performed using both traditional neuropsychological assessment tools, including the Mini-Mental State Examination (MMSE), Montreal Overall Cognitive Assessment (MoCA), and the Smart Aging platform. We analyzed global scores on Smart Aging indices (i.e., accuracy, time, distance) as well as the Smart Aging total score, looking for differences between the four groups. Results: The findings revealed significant between-group differences in all the Smart Aging indices: accuracy (p < 0.001), time (p < 0.001), distance (p < 0.001), and total Smart Aging score (p < 0.001). The HCs outperformed the mild AD, aMCI, and PD-MCI patients in terms of accuracy, time, distance, and Smart Aging total score. In addition, the mild AD group was outperformed both by the HCs and by the aMCI and PD-MCI patients on accuracy and distance. No significant differences were found between aMCI and PD-MCI patients. Finally, the Smart Aging scores significantly correlated with the results of the neuropsychological assessments used. Conclusion: These findings, although preliminary due to the small sample size, suggest the validity of Smart Aging as a screening tool for the detection of cognitive impairment in patients with neurodegenerative diseases.

A double-blind randomized controlled trial of the efficacy of cognitive training delivered using two different methods in mild cognitive impairment in Parkinson's disease: preliminary report of benefits associated with the use of a computerized tool.

BACKGROUND: The effectiveness of computer-based cognitive training (CCT) remains controversial, especially in older adults with neurodegenerative diseases. AIMS: To evaluate the efficacy of CCT in patients with Parkinson's disease and mild cognitive impairment (PD-MCI). METHODS: 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. RESULTS: 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. CONCLUSION: 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).

HomeCoRe for Telerehabilitation in Mild or Major Neurocognitive Disorders: A Study Protocol for a Randomized Controlled Trial.

Background: Given the limited effectiveness of pharmacological treatments for cognitive decline, non-pharmacological interventions have gained increasing attention. Evidence exists on the effectiveness of cognitive rehabilitation in preventing elderly subjects at risk of cognitive decline and in reducing the progression of functional disability in cognitively impaired individuals. In recent years, telerehabilitation has enabled a broader application of cognitive rehabilitation programs. The purpose of this study is to test a computer-based intervention administered according to two different modalities (at the hospital and at home) using the tools CoRe and HomeCoRe, respectively, in participants with Mild or Major Neurocognitive Disorders. Methods: Non-inferiority, single-blind randomized controlled trial where 40 participants with Mild or Major Neurocognitive Disorders will be assigned to the intervention group who will receive cognitive telerehabilitation through HomeCoRe or to the control group who will receive in-person cognitive intervention through CoRe, with the therapist administering the same computer-based exercises. The rehabilitative program will last 6 weeks, with 3 sessions/week, each lasting ~45 min. All the participants will be evaluated on an exhaustive neuropsychological battery before (T0) and after (T1) the intervention; follow-up visits will be scheduled after 6 (T2) and 12 months (T3). Discussion: The results of this study will inform about the comparability (non-inferiority trial) of HomeCoRe with CoRe. Their equivalence would support the use of HomeCoRe for at distance treatment, favoring the continuity of care. Ethics and Dissemination: This study has been approved by the Local Ethics Committee and registered in https://clinicaltrials.gov (NCT04889560). The dissemination plan includes the scientific community through publication in open-access peer-reviewed scientific journals and presentations at national and international conferences. Trial Registration: Clinicaltrials.gov https://clinicaltrials.gov/ct2/show/NCT04889560 (registration date: May 17, 2021).

Effects of Circadian Phase Tailored Light Therapy on Sleep, Mood, and Cognition in Alzheimer's Disease: Preliminary Findings in a Pivotal Study.

It is shown that the circadian system is affected in patients with Alzheimer's disease (AD) even at an early stage of the disease and that such dysfunction may be detrimental to sleep, mood, and cognitive functioning. Light is a strong central modulator of the circadian rhythms and is potentially beneficial to mood and cognitive functioning via a direct effect or indirectly via its modulating effects on circadian rhythms. This study focuses on tracking the effect of light therapy on sleep quality, mood, and cognition in AD of mild/moderate severity. We performed a single-blind randomized controlled trial to investigate the effects of a light therapy treatment tailored to the individual circadian phase as measured by dim light melatonin onset (DLMO). Such a treatment induced an objective circadian phase shift consistent with the melatonin phase response curve to light exposure, led to a shortening of the phase angle DLMO-falling asleep time, and was associated with an improvement in subjective sleep quality and cognitive performance.

Frontal and Cerebellar Atrophy Supports FTSD-ALS Clinical Continuum.

BACKGROUND: Frontotemporal 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. METHODS: We used voxel-based morphometry on structural magnetic resonance images to localize volume alterations in group comparisons: patients (20 FTSD, seven FTSD-ALS, and 18 ALS) versus healthy controls (39 CTR), and patient groups between themselves. We used mean whole-brain cortical thickness ( C T ¯ ) 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. RESULTS: Common (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). C T ¯ values suggested extensive network disruption in the pathological process, with indications of a correlation between cerebral and cerebellar volumes and C T ¯ in ALS. The analysis of the neuropsychological scores indeed pointed toward an important role for the cerebellum, along with fronto-temporal areas, in explaining impairment of executive, and linguistic functions. CONCLUSION: We 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.

Multicenter Study on Sleep and Circadian Alterations as Objective Markers of Mild Cognitive Impairment and Alzheimer's Disease Reveals Sex Differences.

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 < 0.001) and sleep efficiency (SE) lower (p = 0.003) in MCI, and Sleep Regularity Index (SRI) was lower in AD patients compared to controls (p = 0.004). SE was lower in male AD compared to female AD (p = 0.038) and SRI lower in male AD compared to male controls (p = 0.008), male MCI (p = 0.047), but also female AD subjects (p = 0.046). Mesor was significantly lower in males in the overall population. Age reduced the dissimilarities for WASO and SE but demonstrated sex differences for amplitude (p = 0.009) in the overall population, controls (p = 0.005), and AD subjects (p = 0.034). The confusion-matrices showed good predictive power of actigraphic data. CONCLUSION: Actigraphic data could help identify disease or health status. Sex (possibly gender) differences could impact on neurodegeneration and disease trajectory with potential clinical applications.

NREM sleep arousal-related disorders reflect cognitive impairment in Parkinson's disease.

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.

A Machine Learning Approach for the Differential Diagnosis of Alzheimer and Vascular Dementia Fed by MRI Selected Features.

Among dementia-like diseases, Alzheimer disease (AD) and vascular dementia (VD) are two of the most frequent. AD and VD may share multiple neurological symptoms that may lead to controversial diagnoses when using conventional clinical and MRI criteria. Therefore, other approaches are needed to overcome this issue. Machine learning (ML) combined with magnetic resonance imaging (MRI) has been shown to improve the diagnostic accuracy of several neurodegenerative diseases, including dementia. To this end, in this study, we investigated, first, whether different kinds of ML algorithms, combined with advanced MRI features, could be supportive in classifying VD from AD and, second, whether the developed approach might help in predicting the prevalent disease in subjects with an unclear profile of AD or VD. Three ML categories of algorithms were tested: artificial neural network (ANN), support vector machine (SVM), and adaptive neuro-fuzzy inference system (ANFIS). Multiple regional metrics from resting-state fMRI (rs-fMRI) and diffusion tensor imaging (DTI) of 60 subjects (33 AD, 27 VD) were used as input features to train the algorithms and find the best feature pattern to classify VD from AD. We then used the identified VD-AD discriminant feature pattern as input for the most performant ML algorithm to predict the disease prevalence in 15 dementia patients with a "mixed VD-AD dementia" (MXD) clinical profile using their baseline MRI data. ML predictions were compared with the diagnosis evidence from a 3-year clinical follow-up. ANFIS emerged as the most efficient algorithm in discriminating AD from VD, reaching a classification accuracy greater than 84% using a small feature pattern. Moreover, ANFIS showed improved classification accuracy when trained with a multimodal input feature data set (e.g., DTI + rs-fMRI metrics) rather than a unimodal feature data set. When applying the best discriminant pattern to the MXD group, ANFIS achieved a correct prediction rate of 77.33%. Overall, results showed that our approach has a high discriminant power to classify AD and VD profiles. Moreover, the same approach also showed potential in predicting earlier the prevalent underlying disease in dementia patients whose clinical profile is uncertain between AD and VD, therefore suggesting its usefulness in supporting physicians' diagnostic evaluations.

Unsuspected Involvement of Spinal Cord in Alzheimer Disease.

Objective: Brain atrophy is an established biomarker for dementia, yet spinal cord involvement has not been investigated to date. As the spinal cord is relaying sensorimotor control signals from the cortex to the peripheral nervous system and vice-versa, it is indeed a very interesting question to assess whether it is affected by atrophy due to a disease that is known for its involvement of cognitive domains first and foremost, with motor symptoms being clinically assessed too. We, therefore, hypothesize that in Alzheimer's disease (AD), severe atrophy can affect the spinal cord too and that spinal cord atrophy is indeed an important in vivo imaging biomarker contributing to understanding neurodegeneration associated with dementia. Methods: 3DT1 images of 31 AD and 35 healthy control (HC) subjects were processed to calculate volume of brain structures and cross-sectional area (CSA) and volume (CSV) of the cervical cord [per vertebra as well as the C2-C3 pair (CSA23 and CSV23)]. Correlated features (ρ > 0.7) were removed, and the best subset identified for patients' classification with the Random Forest algorithm. General linear model regression was used to find significant differences between groups (p ≤ 0.05). Linear regression was implemented to assess the explained variance of the Mini-Mental State Examination (MMSE) score as a dependent variable with the best features as predictors. Results: Spinal cord features were significantly reduced in AD, independently of brain volumes. Patients classification reached 76% accuracy when including CSA23 together with volumes of hippocampi, left amygdala, white and gray matter, with 74% sensitivity and 78% specificity. CSA23 alone explained 13% of MMSE variance. Discussion: Our findings reveal that C2-C3 spinal cord atrophy contributes to discriminate AD from HC, together with more established features. The results show that CSA23, calculated from the same 3DT1 scan as all other brain volumes (including right and left hippocampi), has a considerable weight in classification tasks warranting further investigations. Together with recent studies revealing that AD atrophy is spread beyond the temporal lobes, our result adds the spinal cord to a number of unsuspected regions involved in the disease. Interestingly, spinal cord atrophy explains also cognitive scores, which could significantly impact how we model sensorimotor control in degenerative diseases with a primary cognitive domain involvement. Prospective studies should be purposely designed to understand the mechanisms of atrophy and the role of the spinal cord in AD.

Cognitive Telerehabilitation for Older Adults With Neurodegenerative Diseases in the COVID-19 Era: A Perspective Study.

The COVID-19 pandemic is a global health problem that is radically transforming public and private healthcare organizations around the world, negatively affecting the rehabilitative treatments of non-COVID pathologies as well. In this situation, it becomes crucial to be able to guarantee the continuity of care also to all those patients with neurodegenerative diseases unable to reach healthcare services. Remote communication technologies are gaining momentum as potentially effective options to support health care interventions-including cognitive rehabilitation-while patients can stay safely at home. In this context, we are implementing HomeCoRe (i.e., Home Cognitive Rehabilitation software) in order to offer an innovative approach and a valid support for home-based cognitive rehabilitation in neurodegenerative diseases, such as mild cognitive impairment and early dementia. HomeCoRe has been developed within a research project between engineers and clinicians in order to obtain a usable and safe cognitive rehabilitation tool. This software has multiple advantages for patients and therapists over traditional approaches, as shown in its use in hospital settings. HomeCoRe could then represent an opportunity for accessing cognitive rehabilitation in all those situations where patients and therapists are not in the same location due to particular restrictions, such as COVID-19 pandemic.

Evening melatonin timing secretion in real life conditions in patients with Alzheimer disease of mild to moderate severity.

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.

HomeCoRe: Bringing Cognitive Rehabilitation at Home.

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.

A computer-based cognitive training in Mild Cognitive Impairment in Parkinson's 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.

Cognitive impairment in depression: recent advances and novel treatments.

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.

Assessment of cognitive profile as a prodromal marker of the evolution of rapid eye movement sleep behavior disorder.

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.

Role of Cerebrospinal Fluid Biomarkers and (18)F-florbetapir PET Imaging in the Diagnosis of Primary Progressive Aphasia: A Retrospective Analysis.

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 Aß1-42 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.

Disease progression in relation to age at onset in a population with Alzheimer's Dementia.

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.