Cristina Pagni

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 Parkinsons 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 Parkinsons 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.

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 Parkinsons 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.

Mild affective symptoms in de novo Parkinson's disease patients: relationship with dopaminergic dysfunction

The investigation of the relationship between affective symptoms and dopamine transporter (DAT) density provided conflicting data in both Parkinsons disease (PD) and non‐PD patients. However, the potential interference of psychoactive as well as anti‐parkinsonian drugs on DAT density should be taken into account.

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65–89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.

Alexithymia is associated with depression in de novo Parkinson's disease

drocephalus, moderate-to-severe vascular abnormalities, and tumors. Exclusion criteria were the presence of a comorbid psychiatric mental disorder or a history of drug abuse. In all de novo PD patients we recorded gender, age, years of education, and the side and the type of motor symptoms’ onset. The severity of motor symptoms was measured by the Unified Parkinson’s Disease Rating Scale (UPDRS II and III) [13] . In all enrolled subjects the global cognitive status was assessed with the Mini-Mental State Examination (MMSE) [14] . Informed consent was obtained in compliance with research standards for human research for all participating institutions and in accordance with the Helsinki Declaration. The TAS-20 is an extensively validated self-report questionnaire comprised of three subscales that investigate the following factors: F1 = difficulty identifying feelings, F2 = difficulty describing feelings, and F3 = difficulty focusing on inner affective experience. The total score on the questionnaire allows categorizing subjects as nonalexithymic (scores ranging from 20 to 51), borderline alexithymic (scores ranging from 52 to 60), or alexithymic (scores 6 61). A 2 test was used for the comparison between qualitative characteristics of the de novo PD subgroups; the Wilcoxon test was used for the comparison of quantitative variables for independent data. All de novo PD patients and all HC were cognitively preserved. Demographic and clinical characteristics of de novo PD patients and HC are reported in table 1 . No differences were found for age, education, cognitive status (MMSE), alexithymia (TAS-20 score) and depression (GDS-15 score) between de novo PD patients and HC. A statistically significant difference was approached for the subscale F2 (p = 0.07). In the group of de novo PD patients, cutoff scores of the TAS-20 identified 10 alexithymic patients (23.80%), 11 borderline alexithymic patients (26.19%) and 21 nonalexithymic patients (50.01%). In the group of HC, 5 subjects were alexithymic (16.6%), 7 subjects were borderline alexithymic (23.3%) and 18 were nonalexithymic (60.1%) ( table 1 ). The difference between frequencies of alexithymia in de novo PD patients (23.80%) and HC (16.6%) was not statistically different (p = 0.33). In the group of de novo PD patients, any difference was found for age, education, cognitive status (MMSE) and motor severity (UPDRS II and III) between alexithymic, borderline alexithymic and nonalexithymic de novo PD patients. Either in the sample of de novo PD patients or in the sample of HC, alexithymic subjects were more depressed at the GDS-15 than nonalexithymic or borderline alexithymic subjects (p ! 0.01) and borderline alexithymic subjects were more depressed than nonalexithymic subjects (p ! 0.01). In the sample of de novo PD patients, the TAS-20 significantly correlated with age (r = 0.343; p = 0.026), with education (r = Alexithymia is a phenomenon related to an alteration in affect regulation. Its characteristics include the inability to identify and describe feelings, difficulty distinguishing feelings from bodily sensations of emotional arousal, impaired symbolization and an externally oriented cognitive style [1] . Alexithymia has been found to be strongly associated with depression in both general [2] and clinical populations [3] . Alexithymic and depressive symptoms may be partially overlapping, but not all are correlated with depressive symptoms, thus underlining the relative independence of the two disorders [4] . Parkinson’s disease (PD) is a clinical condition often characterized by depression and an altered emotional processing [5] . In medicated PD patients alexithymia has a prevalence of 21% [6, 7] and is related to depression [7] . To our knowledge, alexithymia has never been investigated in newly diagnosed untreated (de novo) PD patients before the administration of dopaminergic therapy; this topic is of particular clinical interest considering that affective symptoms may precede the clinical motor onset of PD [8, 9] . This study was aimed at investigating the prevalence of alexithymia in de novo PD patients and its relation to depression. To estimate the prevalence of alexithymia and its relation to depression in de novo PD patients we administered the TwentyItem Toronto Alexithymia Scale (TAS-20) [10] and the Geriatric Depression Scale Short Form (GDS-15) [11] to 42 de novo PD patients and 30 age-matched healthy controls (HC). The de novo PD patients were enrolled in two Italian movement disorder tertiary clinics (Versilia Hospital, Viareggio; Neurological Clinic, University of Pisa). All enrolled patients fulfilled research diagnostic criteria for idiopathic PD [12] . Patients who had clinical features suggestive of primary atypical parkinsonism, such as multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, and those with diagnosis of dementia according to DSM-IV criteria were not included. Magnetic resonance imaging showed no signs of atypical parkinsonism, normal pressure hyReceived: April 15, 2010 Accepted after revision: October 6, 2010 Published online: May 4, 2011

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.

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.

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 Parkinsons 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.

Operationalizing mild cognitive impairment criteria in small vessel disease: The VMCI-Tuscany Study

Mild cognitive impairment (MCI) prodromic of vascular dementia is expected to have a multidomain profile.

Alexithymia is associated with impulsivity in newly-diagnosed, drug-naïve patients with Parkinson's disease: an affective risk factor for the development of impulse-control disorders?

To the Editor: Depression has a high prevalence in patients with Parkinson’s disease (PD) and has been associated with alexithymia, a clinical phenomenon related to an alteration in affect-regulation. We investigated the relationships between symptoms of negative affect (depression and alexithymia) and other neuropsychiatric symptoms in newly-diagnosed, drug-naïve (de novo) PD patients. We enrolled 42 de novo patients who fulfilled research diagnostic criteria for idiopathic PD and 30 age-matched healthy controls (HC). Both groups underwent a neuropsychiatric assessment including the Toronto Alexithymia Scale 20item (TAS-20), the Geriatric Depression Scale Short Form (GDS-15), the Barratt Impulsiveness Scale (BIS-11), the Maudsley Obsessive-Compulsive Questionnaire (MOCQ-R), and the Hamilton Rating Scale for Anxiety (Ham-A). Informed consent was obtained in compliance with research standards for human research for all participating institutions and in accordance with the Helsinki Declaration. PD and HC groups did not differ in age, education, alexithymia, depression, impulsivity or anxiety (Table 1), whereas PD patients reported higher scores, as compared with HC, on theMOCQ-R Total score (p50.038). In both groups, alexithymia correlated significantly with depression (PD: r50.412; p50.007; HC: r50.819; p ,0.001), and impulsivity (PD: r50.316; p50.041; HC: r50.452; p50.027). In each group, stepwise regression analyses showed that alexithymia predicted depression (PD: F514.696; p ,0.001; HC: F544.926; p ,0.001), and impulsivity (PD: F55.063; p50.029; HC: F55.642; p50.027). Considering TAS-20 factors (F-1: Difficulty Identifying Feelings; F-2: Difficulty Describing Feelings; F-3: Difficulty Focusing on Inner Affective Experience), depression was predicted by F-1 in PD (F518.718; p,0.01) and by F-2 in HC (F538.47; p ,0.01), and impulsivity was predicted only by F-1 in both groups (PD: F54.812; p ,0.05; HC: F513.450; p50.01). In de novo PD patients, as in HC, alexithymia was associated with depression and impulsivity, but these neuropsychiatric features were not associated. In addition to the known association between alexithymia and depression in both groups, impulsivity was predicted by alexithymia, and, considering TAS-20 factors, only by the TAS-20 F-1 factor. This finding is partially at variance with findings reported in a study with healthy subjects, in which impulsivity was not found to be associated with the TAS-20 total score, in contrast with our study, but only with the TAS-20 F-1 factor, as we found for PD and HC. Therefore, alexithymic difficulty in identifying one’s own feelings could factor into situations where there is rapid respond to cues for potential reward without much planning or deliberation and without consideration of potential punishment or loss of reward, as defines impulsivity. Considering that dopamine agonists adopted to treat PDmotor symptoms may increase impulsivity and the risk of developing impulse-control disorders, the clinical implication of this finding is that the presence of alexithymic features, especially the difficulty in identifying one’s own feelings, could represent a risk factor for the development of impulsecontrol disorders when patients are treated with dopamine agonists. This hypothesis, which deserves further