Mild Cognitive Impairment in de novo Parkinson's Disease: Selective Attention Deficit as Early Sign of Neurocognitive Decay.

Background: In the present study, we aimed to better investigate attention system profile of Parkinson's disease-Mild Cognitive Impairment (PD-MCI) patients and to determine if specific attentional deficits are associated with 123I-FP-CIT SPECT. Methods: A total of 44 de novo drug-naïve PD patients [(27) with normal cognition (PD-NC) and 17 with MCI (PD-MCI)], 23 MCI patients and 23 individuals with subjective cognitive impairment (SCI) were recruited at the Clinical Neurology Unit of Santa Chiara hospital (Pisa University Medical School, Italy). They were assessed by a wide neuropsychological battery, including Visual Search Test (VST) measuring selective attention. Performances among groups were compared by non-parametric tests (i.e., Kruskal-Wallis and Mann-Whitney, Bonferroni corrected). Further, Spearman's rank correlations were performed to explore the association between neuropsychological variables and 123I-FP-CIT SPECT data in PD subgroup. Results: PD-MCI patients performed worse on VST than patients with PD-NC (p = 0.002), patients with MCI and individuals with SCI (p < 0.001). The performance of PD-MCI patients on VST significantly correlated with caudate nucleus 123I-FP-CIT SPECT uptake (rho = 0.582, p < 0.05), whereas a negative correlation between such test and 123I-FP-CIT SPECT uptake in the left putamen (rho = -0.529, p < 0.05) was found in PD-NC patients. Conclusions: We suggest that selective attention deficit might be a trigger of cognitive decay in de novo PD-MCI patients. The VST should be routinely used to detect attentional deficits in hospital clinical practice, in the light of its closely association with dopamine depletion of basal ganglia in mildly impaired PD patients.

Healthy aging: the INTECMAN project.

Aging is associated not only with the reduction of psychophysical and sensory capacities but also with different types of neurodegenerative disorders up to dementia manifestations. Aging in health and self-sufficiency is strictly dependent on the prevention and correction of factors that may determine reduction of psychophysical capacities (e.g., cardiovascular, locomotor and neurodegenerative ones). To reach this goal, due to the dynamics of social and family changes and to the aging of the population, health professionals can be supported by technologies which provide noninvasive monitoring of physiologic parameters and rely on telemedicine, both instruments of support and care for better aging in the home setting. The authors, starting from the initial idea of a personalized monitoring of different psychophysical variables, defined a pilot study to assess the role of a 12-month individually tailored lifestyle counseling on parameters of mild cognitive impairment in a group of elderly subjects. Data derived from the applied approach appeared promising and may open the road to the possible implementation of individual counseling, based on multiparametric non-obtrusive technologies which take into consideration both psychological and physical aspects, to be followed in the home environment.

Connected speech in progressive supranuclear palsy: a possible role in differential diagnosis.

BACKGROUND: Progressive supranuclear palsy (PSP) is an atypical Parkinsonism characterized by motor and neuropsycological disorders. Language could be impaired in PSP patients, also in Richardson variant (PSP-RS). The analysis of connected speech is used in neurodegenerative disorder to investigate different levels of language organization, including phonetic, phonological, lexico-semantic, morpho-syntactic, and pragmatic processing. OBJECTIVE: In our study, we aimed to investigate the language profile, especially connected speech, in early-stage PSP-RS and Parkinson's disease (PD) patients without predominant speech or language disorders. METHODS: Language was assessed using the Screening for Aphasia in NeuroDegeneration (SAND); connected speech analysis was conducted from the picture description subtest. RESULTS: We enrolled 48 patients, 22 PD and 26 PSP (18 PSP-RS and 8 non-RS). PSP-RS patients presented an impairment in language domain, particularly regarding connected speech. PSP-RS patients presented worse performances than PD in different scores. The output of PSP-RS patients was characterized by a reduction in number of sentences and subordinates with respect to PD; PSP presented also more repaired sequences and phonological and lexico-semantic errors than PD. Number of sentences and number of subordinates of the picture description task were identified as predictors of PSP diagnosis. CONCLUSION: In summary, the SAND scale is able to identify language impairment in PSP patients. The analysis of connected speech could highlight some important aspects of language impairment in PSP-RS patients, and it could be helpful in the differential diagnosis with PD.

Theory of mind in Parkinson's disease: evidences in drug-naïve patients and longitudinal effects of dopaminergic therapy.

Theory of mind (ToM) is the ability to attribute mental states to one self and others and to understand that others have beliefs different from one's own. Different subcomponents of ToM have also been identified: cognitive and affective. Cognitive ToM refers to the capacity to infer others' beliefs and intentions, while affective ToM implies the ability to appreciate others' emotional states. The aim of this study was to explore ToM in drug-naïve Parkinson's disease (PD) patients and to investigate the effects of chronic dopaminergic therapy on different subcomponents of ToM during a 3 months and 1 year of follow-up. We examined 16 PD patients in three conditions: before (un-medicated) and after dopaminergic therapy (medicated 3 months: T1 and medicated 1 year: T2). We also compared our PD's ToM abilities with 11 healthy individuals. ToM was explored with 5 different tasks: Faux Pas Test, Picture Sequencing Task Capture Story, Emotion Attribution Task, Strange Stories Task, and Karolinska Directed Emotional Faces. Our study confirms that PD patients present deficits in cognitive components of ToM and preserved performances in the affective ones in early stages of disease. We also find a significant effect of dopaminergic therapy on ToM already after 3 months with a good persistency after 1 year of treatment.

Functional magnetic resonance imaging with encoding task in patients with mild cognitive impairment and different severity of leukoaraiosis.

Leukoaraiosis is one of the main contributors to mild cognitive impairment due to vascular damage (vascular MCI, VMCI), whose pathophysiology has not been fully elucidated yet. We aimed to shed light on such issue using functional MRI (fMRI). Sixteen patients with VMCI were enrolled and compared with twenty-five patients with MCI but without significant vascular damage (non-vascular MCI, NVMCI) and with fifteen healthy controls (HC). They all underwent fMRI with incidental verbal learning paradigm, using a 3T scanner. Differently from cases with NVMCI (versus HC), VMCI patients presented a higher BOLD activation in the right parieto-occipital cortex and a lower activation in the left superior and middle frontal gyri, anterior cingulum and in left fronto-opercular area when compared to HC. Cortical activation evaluated by fMRI may reflect specific patterns of damage and attempt of compensation in patients with MCI and different severity of leukoaraiosis.

Social Cognition and Oxytocin in Huntington's Disease: New Insights.

This study is aimed at relating social cognition in Huntington's Disease (HD) to plasma levels of the social hormone oxytocin (OT). Indeed, HD patients commonly display reduced social skills and OT is involved in bonding behavior and improved recognition of facial emotions. Twelve mild-symptomatic HD patients (stage II Shoulson & Fahn) and 11 gender/age matched controls (healthy controls, HC), without concurrent psychiatric disorders, were investigated at baseline (T0) for OT plasma levels and social cognition through an extensive battery of neuropsychological tests. Social cognition was also re-examined after two years (T1) in 8 of the 12 patients. Results showed a trend for reduced T0-OT levels in HD vs. HC, mean ± stardard deviation: 6.5 ± 2.4 vs. 9.9 ± 7.2 pg/mL, without reaching statistical significance. At T0, patients showed significantly lower performances than controls at the "Faux-Pas" and "Strange Stories" tests (p < 0.05; p < 0.01); a reduced perception of visual emotions (p < 0.01) and verbal stimuli (p < 0.01) was also reported, involving anger, fear, and sadness (p < 0.05; p < 0.01). Additionally, in the HD population, OT concentrations positively correlated with T1-performances at Neutral\Faux-Pas test (p < 0.05), whereas the cognitive Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) scores positively correlated with psychosocial perception at the "Strange Stories" and Karolinska Directed Emotional Faces (KDEF) tests (p < 0.05). This study, despite its limitations, supports correlations between OT and HD social cognition, suggesting a possible therapeutic use of this hormone. More subjects and additional body tissues/fluids, such as cerebrospinal fluid, should be investigated to confirm this hypothesis.

Oxidative Stress Assessment in Alzheimer's Disease: A Clinic Setting Study.

BACKGROUND: Oxidative stress (OS) is a physiological age-related brain process, dramatically overexpressed in neurodegenerative disorders like Alzheimer's disease (AD). Nevertheless, the pathophysiological role of OS in AD pathology has not been clarified yet. OS as a biomarker for AD is a controversial issue. A comparison of previous data is difficult due to a remarkable methodological variability. Most of the previous studies have shown higher levels of OS markers and lower antioxidant power in patients with dementia when compared to mild cognitive impairment (MCI) and healthy controls. METHODS: We followed a strict protocol in order to limit intrasite variability of OS assessment. In addition, we have taken into account possible confounding factors. RESULTS: In agreement with previous reports, we found both lower plasmatic OS and higher plasmatic antioxidant defenses when comparing patients with AD having dementia that is stably treated to patients with MCI-AD. DISCUSSION: A speculative hypothesis based on correlative data is provided.

A single center study: Aß42/p-Tau181 CSF ratio to discriminate AD from FTD in clinical setting.

Abnormal levels of beta amyloid (Aß42) and tau protein concentrations in the cerebral spinal fluid (CSF) have been largely described in Alzheimer's disease (AD). Thus, CSF analysis of these biomarkers has been incorporated in recent AD diagnostic criteria, and it is increasingly performed for neurodegenerative dementia diagnostic workout in clinical setting. Nevertheless, the precise biomarkers CSF features in neurodegenerative dementia, either AD or Frontotemporal dementia (FTD), are still not fully clear today. This is mainly due to lack of CSF clear cutoff values due to a well-known intersite (but even intrasite) variability of CSF procedures, ranging from collection to analysis. Applying CSF biomarker ratios, rather than their single values could represent a useful tool, especially for the differential diagnosis of different forms of dementia. We explored clinical values of six CSF ratios (by combining Aß42 and tau) in order to better discriminate between AD and FTD; we identified Aß42/p-Tau181 ratio as a potential good candidate for helping differentiating AD from FTD in the clinical practice.

Social cognition in Juvenile Myoclonic Epilepsy.

OBJECTIVE: Juvenile Myoclonic Epilepsy (JME) is a common genetic generalized epilepsy syndrome. Several studies have detailed cognitive and imaging abnormalities pointing to frontal lobe dysfunction, as well as disadvantageous behavioral traits and poor social outcome, challenging the commonly held view of JME being a benign disorder. Social cognition is the ability to elaborate mental representations of social interactions and to use them correctly in social contexts, and includes Theory of Mind (ToM), which pertains to the attribution of cognitive and affective mental states to self and others and seems to rely on complex fronto-temporal interactions. ToM has been recently assessed in focal epilepsy syndromes, but little is available for generalized epilepsies. We performed a cross-sectional study to assess social cognition, with an emphasis on ToM, as well as standard cognitive functions in patients with JME. METHOD: We recruited twenty JME patients and twenty matched controls. Tests used to assess social cognition and ToM included the Emotion Attribution Task, Strange Stories Task (SST), Faux Pas Task (FPT), Reading the Mind in the Eyes Task and Social Situation Task. Subjects were also assessed via an extensive neuropsychological battery. RESULTS: Patients exhibited worse performance in the SST and in several scores of the FPT. They also showed widespread cognitive impairment, involving executive functions, psychomotor speed, verbal and visuo-spatial memory. CONCLUSIONS: In addition to cognitive impairment for fronto-temporal tasks, some features of social cognition are also altered in JME. The latter deficit may underlie the poor social outcome previously described for these patients, and might also relate to imaging findings of frontal lobe dysfunction.

A pilot psychometric study of aberrant salience state in patients with Parkinson's disease and its association with dopamine replacement therapy.

An overactive striatal dopaminergic neurotransmission is described in psychosis and may be associated with a state of aberrant salience attribution. This pilot psychometric study investigated if features suggestive of an aberrant salience state, a condition of psychosis proneness, are associated with dopamine replacement therapy in patients with early Parkinson's disease (PD). 77 participants (50 medicated PD patients, 12 newly diagnosed drug-naive PD patients and 15 healthy controls) were enrolled and assessed with the Aberrant Salience Inventory (ASI). Differences between groups were found for ASI scores, and ASI scores correlated with the dopaminergic therapy, in particular levodopa. These findings preliminary suggested that the presence and the degree of an aberrant salience state may be associated with features of the dopaminergic therapy; further studies are needed to investigate which neuropsychiatric complications more common in PD patients may be characterized by an underlying aberrant salience state.

The relationship between motor symptom lateralization and cognitive performance in newly diagnosed drug-naïve patients with Parkinson's disease.

The side of motor symptom predominance may influence cognitive performance in patients with Parkinson's disease (PD): PD patients with right-side motor symptom predominance typically present difficulties in tasks of language and verbal memory, whereas PD patients with left-side motor symptom predominance typically present difficulties in visuospatial tasks. The current study aimed at investigating the relationship between motor symptom lateralization and cognitive performance in PD patients without the possible confounding effect of dopaminergic drugs, which may enhance or impair cognition on the basis of assessed function and disease stage. From the initial sample of 137 consecutive newly diagnosed drug-naïve (de novo) PD patients, clinical follow-ups and neurological examinations identified 108 right-handed patients with a unilateral motor presentation or a clear motor asymmetry (59 right-PD: 54.6%; 49 left-PD: 45.4%). Any cognitive difference emerged between right-PD patients and left-PD patients at this disease stage. Scores of lateralized motor impairment severity correlated with some cognitive performances: Right motor impairment correlated with a measure of set shifting (Trail Making Test B-A), and left motor impairment correlated with phonemic fluency and tasks with visuospatial material (Colored Progressive Matrices of Raven, Rey-Osterrieth Complex Figure Copy and Immediate Recall). Findings of the current study supported the conclusion that the side of clinical motor predominance scarcely influences cognition in the early untreated stages of PD, suggesting that cognitive differences between subgroups of lateralized PD patients probably may appear in more advanced disease stages.

The epidemiology and clinical manifestations of dysexecutive syndrome in Parkinson's disease.

This mini-review summarizes the evidence of the cognitive and behavioral features of dysexecutive syndrome in Parkinson's disease (PD). Deficits in response inhibition, set-shifting, mental flexibility, and strategy have been frequently described from the earliest stages of PD, although there are inconsistencies in study findings due to the complexity of the executive function (EF) construct and methodological limitations. Behavioral disorders of PD, e.g., apathy, distractibility, perseverative behavior, and impulse-control disorders, may be viewed as the other side of dysexecutive syndrome. Despite the interrelationship between the cognitive and behavioral domains, some reports reveal that the two syndromes may be dissociated, suggesting that both aspects must be clinically assessed. EFs are widely associated with the prefrontal areas, although dysexecutive syndrome may be observed in patients with damage to other brain regions. EFs drive numerous abilities essential to daily life, such as prospective remembering and language comprehension, which may be impaired in PD subjects. Considering the impact of dysexecutive syndrome on independence and quality of life, early detection of executive impairment is crucial in the management of PD.

Mild cognitive impairment and cognitive-motor relationships in newly diagnosed drug-naive patients with Parkinson's disease.

BACKGROUND AND AIMS: (1) To establish the prevalence of mild cognitive impairment (MCI) in newly diagnosed drug-naive patients with Parkinson's disease adopting recently proposed and more conservative preliminary research criteria. (2) To investigate the relation between cognitive performances, MCI and motor dysfunction. METHODS: 132 consecutive newly diagnosed drug-naive PD patients and 100 healthy controls (HCs) underwent a neuropsychological evaluation covering different cognitive domains. Moreover, on the basis of the Unified Parkinson's Disease Rating Scale II/III, different motor scores were calculated and patients were classified in motor subtypes. 11 patients were excluded from the analysis during clinical follow-up which was continued at least 3 years from the diagnosis; therefore, the final sample included 121 patients. RESULTS: MCI prevalence was higher in PD (14.8%) patients than in HCs (7.0%). PD patients reported lower cognitive performances than HCs in several cognitive domains; HCs also outperformed cognitively preserved PD patients in tasks of episodic verbal memory and in a screening task of executive functions. MCI-PD patients presented a more severe bradykinesia score than non-MCI PD patients and patients mainly characterised by tremor had better performances in some cognitive domains, and specific cognitive-motor relationships emerged. CONCLUSIONS: Although the adoption of more conservative diagnostic criteria identified a lower MCI prevalence, we found evidence that newly diagnosed drug-naive PD patients present a higher risk of MCI in comparison with HCs. Axial symptoms and bradykinesia represent risk factors for MCI in PD patients and a classification of PD patients that highlights the presence/absence of tremor, as proposed in this study, is probably better tailored for the early stages of PD than classifications proposed for more advanced PD stages.

Alexithymia may modulate decision making in patients with de novo Parkinson's disease.

The aim of this study was to investigate whether and how alexithymia may influence decision making under conditions of uncertainty, assessed using the Iowa Gambling Task, in patients with newly diagnosed, untreated (de novo) Parkinson's disease, as previously reported for healthy subjects. Twenty-four patients with de novo Parkinson's disease underwent a neuropsychological and neuropsychiatric assessment, including the Toronto Alexithymia Scale, the Geriatric Depression Scale Short Form, and the Iowa Gambling Task (IGT). The assessment showed that 12 patients were alexithymic and 12 were non-alexithymic; seven patients were found to be mildly depressed and 17 non-depressed. Alexithymic and non-alexithymic patients did not differ in the IGT total score; however, significant differences emerged across the third block of the IGT, in which the alexithymic patients outperformed the nonalexithymic patients. Depression did not influence IGT performance. Alexithymia may modulate decision making, as assessed with the IGT; alexithymia could be associated with faster learning to avoid risky choices and negative feedback, as previously reported in some studies conducted in anxious or depressed patients.

Event-based prospective memory in newly diagnosed, drug-naive Parkinson's disease patients.

The present study investigated memory for intention in individuals with Parkinson's disease (PD) who were newly diagnosed and not yet treated to avoid the effect of therapy as a potential confounding variable. A comprehensive neuropsychological battery and an event-based prospective memory task were administered to 41 subjects with de novo PD and 40 control subjects. Separate scores were computed for correct execution of intended action (prospective component) and recall of intention (retrospective component). PD patients performed marginally worse (p = .053) than controls on the prospective component of the task. On the other hand, the performance of the two groups was comparable for the retrospective component. Neuropsychological findings revealed lower performance of the PD group in episodic memory and in some measures of executive functions. These results suggested a subtle prospective memory dysfunction present at the initial stage of PD, which may be related to disruption of fronto-striatal circuitry.

Dopamine Transporter SPECT Imaging in Corticobasal Syndrome.

OBJECTIVE: To investigate dopaminergic function in a large cohort of patients with corticobasal syndrome (CBS) and describe its relationship with clinical features in comparison to Parkinson's disease and healthy control subjects. In addition, we assessed prevalence and features of individuals with CBS and in vivo evidence of preserved nigral neuronal density. BACKGROUND: Substantia nigra pars compacta (SNc) neuronal degeneration is a mandatory pathological criterion for definite corticobasal degeneration, though sporadic autopsy-proven cases with ante-mortem imaging evidence of preserved nigral terminals have been recently described. METHODS: In this multicenter study, we investigated presynaptic nigrostriatal function in 36 outpatients fulfilling clinical criteria for "probable corticobasal degeneration" (age 71±7.3 years; disease duration 3.9±1.6 years), 37 PD and 24 healthy control subjects using FP-CIT single photon emission computed tomography. Clinical, neuropsychological, and magnetic resonance imaging assessment was performed to characterize CBS patients. Linear discriminant analysis was used to categorize normal vs. pathological scans. RESULTS: FP-CIT binding reduction in patients with CBS was characterized by larger variability, more uniform reduction throughout the striatum and greater hemispheric asymmetry compared to PD. Moreover, there was no significant correlation between tracer uptake values and clinical features such as disease duration and severity. Despite all CBS subjects showed obvious bilateral extrapyramidal signs, FP-CIT uptake was found to be normal bilaterally in four CBS patients and only unilaterally in other four cases. Extensive clinical, neuropsychological and imaging assessment did not reveal remarkable differences between CBS subjects with normal vs. pathological FP-CIT uptake. CONCLUSIONS: Our findings support the hypothesis that extrapyramidal motor symptoms in CBS are not invariably associated with SNc neuronal degeneration and that supranigral factors may play a major role in several cases. CBS individuals with normal FP-CIT uptake do not show any clinical or cognitive feature suggesting a different pathology than CBD.

The association between motor subtypes and alexithymia in de novo Parkinson's disease.

This study aimed at investigating the association between motor subtypes and alexithymic features in patients with newly diagnosed untreated (de novo) Parkinson's disease. This objective derived from empirical findings about an association between the postural instability/gait difficulty motor subtype of Parkinson's disease and more marked symptoms of depression, an affective disorder strongly related to alexithymia. A total of 42 patients with de novo Parkinson's disease underwent neuropsychiatric assessment, including the toronto alexithymia scale (TAS-20) and the geriatric depression scale (GDS-15). On the basis of scores reported at the unified Parkinson's disease rating scale III section, patients were classified within postural instability/gait difficulty motor subtype tremor dominant motor subtype and mixed motor subtype. Patients of the postural instability/gait difficulty motor subtype reported significantly higher alexithymic features compared to patients of the other motor subtypes. Considering the strong association between alexithymia and depression, this finding is in line with previous findings reporting that the postural instability/gait difficulty subtype of Parkinson's disease is associated to more marked psychopathological features, especially affective features (depression and apathy). In conclusion this brief report suggests the usefulness of an early neuropsychiatric assessment of affect regulation difficulties in PD patients, especially in those with a prevalence of akinetic/rigid symptoms.