Cognitive reserve maps the core loci of neurodegeneration in corticobasal degeneration.

BACKGROUND AND PURPOSE: Cognitively stimulating life experiences and activities are deemed to moderate the clinical impact of brain damage progressively building a neural and cognitive reserve (CR). CR has been studied extensively in various neurodegenerative disorders, but not in corticobasal degeneration (CBD). METHODS: Using Statistical Parametric Mapping 8, years of education, as a determinant of CR, was correlated with tracer uptake on positron emission tomography with 18 F-fluorodeoxyglucose, as a marker of neurodegeneration, in 35 patients with various phenotypes of CBD, including a cognitive-motor composite score or symptoms duration as covariates for controlling disease stage. RESULTS: A cluster of relative hypometabolism was found associated with higher education in the left inferior regions of pre- and post-rolandic gyri and insula, which represent typical loci of neurodegeneration in CBD regardless of clinical presentation. CONCLUSIONS: The present findings extend to CBD the evidence gathered in other neurodegenerative disorders that a higher CR has a protective effect against the clinical manifestations of brain degeneration.

Validation and attempts of revision of the MDS-recommended tests for the screening of Parkinson's disease dementia.

The Movement Disorders Society (MDS) formulated diagnostic criteria and assessment guidelines for the screening of dementia in Parkinson's disease (PD). We carried out a validation of the cognitive measures suggested in the screening algorithm (i.e. the Mini Mental State Examination - MMSE - total score, serial 7s subtraction, 3-word recall, pentagons copy, and one minute letter fluency) in 86 patients with PD. Thirty-six percent of participants were diagnosed with dementia using the MDS algorithm, but with the Dementia Rating Scale instead of the MMSE. The original MDS procedure misclassified 11 patients (12.8%) as false negatives and 3 (3.5%) as false positives, leading to 65% sensitivity and 95% specificity. The main reason for misdiagnoses was insensitivity of the MMSE total score. Three attempts were made to reach a better screening performance, which warrants high sensitivity more than high specificity: 1. exclusion of the MMSE total score as a diagnostic requirement; 2. determination of a better cut off through Receiver Operating Characteristic curve analysis; 3. replacement of the MMSE with the equally undemanding, but more PD-specific, Mini Mental Parkinson. The first two strategies generally yielded high sensitivity, but poor specificity. The best outcome was achieved using a Mini Mental Parkinson total score <27 as cognitive criterion: sensitivity was 87% and negative predictive value was 90%; however, specificity was only 67%. Our findings seem to suggest that MDS practical guidelines are specific, but might benefit from the use of more PD-oriented tools than the MMSE in terms of sensitivity.

Psychometric properties of the Italian version of the Scales for Outcomes in Parkinson's disease- Cognition (SCOPA-Cog).

The Scales for Outcomes in Parkinson's disease-Cognition (SCOPA-Cog) has been shown to be a clinimetrically rigorous and valid instrument for a disease-oriented neuropsychological assessment of Parkinson's disease (PD) patients. In the present study we evaluated the psychometric properties of the Italian version of the SCOPA-Cog in 121 PD patients. The scale explores memory, attention, and executive and visuospatial functions and takes approximately 20 minutes to administer. Data distribution (skewness= -0.23) and internal consistency (Cronbach's alpha= 0.78) were satisfactory. Standard error of measurement was 3.42. The outcome was significantly worse in patients with an abnormal Psychometric properties of the Italian version of the Scales for Outcomes in Parkinson's disease-Cognition (SCOPA-Cog) score on the Dementia Rating Scale (DRS) (SCOPACog mean score 14.6 ± 5.1 out of a total of 43) with respect to cognitively intact subjects (24.2 ± 4.3) (p<0.0001). The DRS showed good convergent validity (Spearman rho= 0.77, p<0.0001), and a high coefficient of variation (= 0.34). These findings support the goodness of the Italian SCOPA-Cog in terms of metrics and validity.

Diagnosis of possible mild cognitive impairment in Parkinson's disease: validity of the SCOPA-Cog.

The detection of cognitive decline in Parkinson's disease (PD), at the Mild Cognitive Impairment (MCI) stage, has prognostic and treatment implications. The Movement Disorders Society (MDS) has recently published criteria and guidelines for the diagnosis of possible and probable PD-MCI. In the present study we assessed the ability of the Scales for Outcomes in Parkinson's disease-Cognition (SCOPA-Cog) to discriminate possible PD-MCI cases from patients with PD-dementia (PDD) and from cognitively intact PD subjects. Hundred-and-thirteen consecutive PD patients underwent the MMSE, the Dementia Rating Scale and an interview on independence in daily living, and were classified as cognitively intact (n = 49), or as possible PD-MCI (n = 33) or PDD (n = 31), according to MDS criteria. Logistic regression analysis was carried out with PD-MCI diagnosis (yes/no) as an outcome variable, and age, education and the SCOPA-Cog total score as covariates. Classification of cases according to the regression model was used for constructing Receiver Operating Characteristic (ROC) curves. Area Under the Curve (AUC) was 0.92 [95% CI 0.86-0.98], for the differential diagnosis between PD-MCI and cognitively normal patients, and 0.97 [95% CI 0.80-1.00], for the differential diagnosis between PD-MCI and PDD. Sensitivity and specificity were 90% and 73% for the PD-MCI versus no cognitive impairment differentiation, at the cutpoint ≥24, and 93% and 97% for the PD-MCI versus PDD discrimination, at the cutpoint ≥17. The SCOPA-Cog is a quick and psychometrically sound PD-specific scale. Our findings support its use for the screening of possible PD-MCI.

Validity and metric of MiniMental Parkinson and MiniMental State Examination in Parkinson's disease.

The MiniMental Parkinson (MMP) has been derived from the MiniMental State Examination (MMSE) for the screening of cognitive impairment in Parkinson's disease by adding subtests that were focused on executive and visuo-spatial impairment more than on memory or language deficits. In this multicenter study, the psychometric and validity properties of the MMP have been evaluated in 69 cognitively intact and 52 cognitively impaired patients with Parkinson's disease, classified according to their performance at the Dementia Rating Scale. The MMP showed better metrics and convergent validity, and higher screening ability. However, its performance was not fully satisfying in terms of data distribution, coefficient of variation and specificity, and Receiver Operating Characteristic curves did not show clear cut superiority of either scale at their best sensitivity-specificity trade off. The MMP seems to be slightly preferable to the MMSE only at a cut off that favours sensitivity with respect to specificity, for screening purposes. The test is simple and quick, but has limitations in terms of validity.

Frequency and clinical features of Lewy body dementia in Italian memory clinics.

BACKGROUND: The latest developments in Lewy Body Dementia (DLB) raise some controversies on clinical features, neuroimaging and therapy. The aim of our study is to determine clinical, neuropsychological, neuroimaging and EEG profile of DLB through retrospective and prospective data of 102 patients. METHODS: data were collected with an analytical form that was developed by an expertise of neurologists. RESULTS: DLB represented 4.8% of the dementia population, with no sex difference. Family history of dementia was common (24.5%), while familiarity for parkinsonism was rare (4.9%). Cognitive disturbances were the predominant clinical presentation at onset (49%), followed by behavioral symptoms (29.4%) and parkinsonism (21.6%). Clinical features at consultation were: memory disturbances (almost all cases), symmetrical (68.6%) or asymmetrical (18.6%) parkinsonism, cognitive fluctuations (49%), visuospatial deficits (53.9%), and visual hallucinations (44.1%). Autonomic signs were present in a third of the cases, while sleep disorders were present in 44.1%. Some clinical response to antiparkinsonian drugs was evident in half of the cases. MRI, SPET, EEG and Neuropsychiatric Inventory data were available in a subgroup of patients. CONCLUSIONS: Most of our data were in accordance with the previous literature. However, some data underline the relationship between DLB, Alzheimer's and Parkinson's disease.

Extracorporeal photochemotherapy: a safety and tolerability pilot study with preliminary efficacy results in refractory relapsing-remitting multiple sclerosis.

Extracorporeal photochemotherapy (ECP) is an immunomodulating procedure consisting of autologous reinfusion of peripheral blood mononuclear cells (PBMC) after direct exposure to 8-methoxy-psoralen and UV-A. It has been described as a successful treatment for different T-cell-mediated diseases and preliminary results suggest that ECP might be effective in the treatment of relapsing-remitting multiple sclerosis, but does not significantly alter the course of the progressive form of MS. In this study, we report the safety data and some preliminary efficacy evidence obtained using ECP in the treatment of five patients with refractory relapsing-remitting (RR) MS: in most cases ECP induced a reduction in the relapse rate and an EDSS stabilisation, with an apparent general MRI stabilisation. In conclusion, our results confirm ECP safety and tolerability and suggest that this treatment might be useful as a therapeutic alternative in the subgroup of RRMS patients not responsive to or not eligible for traditional immunomodulating or immunosuppressive treatments.

Clinical correlates and cognitive underpinnings of verbal fluency impairment after chronic subthalamic stimulation in Parkinson's disease.

A decline in verbal fluency is the most consistent neuropsychological sequela of deep brain stimulation (DBS) for Parkinson's disease. We assessed clinical correlates and switching and clustering subcomponents in 26 parkinsonians undergoing subthalamic DBS. Post-surgical motor improvement was accompanied by worsening at both letter and category fluency tasks. Total number of words and switches decreased, while average cluster size was unchanged. Worsening tended to be prominent in patients with baseline poorer cognitive status and more depressed mood. Impairment of shifting suggests prefrontal dysfunction, possibly due to disruption of fronto-striatal circuits along the surgical trajectory and/or to high frequency stimulation itself.

Discriminative and predictive power of an informant report in mild cognitive impairment.

BACKGROUND: The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) requires caregivers to rate decline in patients' cognitive and functional performance and has never been used for mild cognitive impairment (MCI). METHODS: We contrasted the discriminative and predictive power of the IQCODE with that of the Mini Mental State Examination (MMSE) and a verbal episodic memory measure, the Rey's Auditory Verbal Learning Test (RAVLT), in 45 patients with MCI (mean (SD) age at baseline: 71.6 (4.7) years) and 30 outpatients with dementia (70.5 (6.3) years) attending the Neuropsychology Service, St Gerardo Hospital, and compared them with 55 cognitively intact elderly people (70.7 (7.1) years). Patients with MCI were followed up for at least 2 years or until conversion to dementia. RESULTS: In total, 24 patients with MCI (53.3%) had converted to dementia at follow up (mean (SD) duration of follow up 17.0 (7.3) months for converters and 35.0 (7.1) months for non-converters). At baseline, the ability to differentiate patients with MCI from healthy controls was similar for the IQCODE (area under the curve (AUC) 0.86) and the MMSE (AUC 0.84; z = 0.53, not significant). As predictors of conversion to dementia, a trend favouring the IQCODE (AUC 0.86) with respect to immediate (AUC 0.74) and delayed (AUC 0.75) recall on the RAVLT was apparent (z = 1.36, p = 0.087 versus immediate recall, z = 1.51, p = 0.064 versus delayed recall). The independent predictive ability of IQCODE and memory scores was evaluated through logistic regression, and the questionnaire alone yielded the best correct classification of 81%. CONCLUSIONS: The IQCODE is an informant based measure of cognitive decline that may provide a relevant contribution to the diagnostic and prognostic investigation of patients with MCI.

Ineffectiveness of an Italian NART-equivalent for the estimation of verbal learning ability in normal elderly.

Comparison between current and premorbid memory ability may be of help when trying to make a timely diagnosis of cognitive decline in questionable dementia. In the present study, we evaluated the possibility of estimating episodic verbal memory scores at the Rey Auditory Verbal Learning Test (RAVLT) from an irregular words reading task held to resist to deterioration, that is the Italian analogue of the NART, the TIB (Test d'Intelligenza Breve--brief intelligence test). A regression analysis was performed in a large sample of healthy elderly, using RAVLT scores as dependent variable and TIB score, MMSE score, age and education as predictors. We failed to find a relationship between the two tests that was strong enough for a reliable estimation of memory ability.

The Frontal Assessment Battery (FAB): normative values in an Italian population sample.

The Frontal Assessment Battery (FAB) is a short cognitive and behavioural six-subtest battery for the bedside screening of a global executive dysfunction; although recently devised, it is already extensively used thanks to its ease of administration and claimed sensitivity. The aim of the present study was to derive Italian normative values from a sample of 364 control subjects (215 women and 149 men) of different ages (mean: 57.4+/-17.9 years; range: 20-94 years) and educational level (mean: 10.4+/-4.3 years; range: 1-17 years); the Mini Mental State Examination (MMSE) was concurrently administered. Multiple linear regression analysis revealed significant effects for age and education whereas gender was not significant; thus, from the derived linear equation, a correction grid for FAB raw scores was built. Based on nonparametric techniques, inferential cut-off scores were subsequently determined and equivalent scores (ES) computed. Test-restest and interrater reliabilities were both satisfactory. Interestingly, MMSE was significantly correlated with FAB raw scores, whereas adjusted scores were not. The present data may improve the accuracy in the use of the FAB both for clinical and research purposes.

Unconventional affective symptoms and executive functions after stroke in the elderly.

In the present study we assessed the presence and severity of unconventional affective symptoms (apathy, anhedonia and emotional lability) and depression in 33 elderly patients with first ever stroke and evidence of a single supratentorial lesion at neuroimaging. Patients were submitted to neurological, functional, and affective assessment at a mean interval of 2 weeks after stroke onset. Given the putative role of the frontal lobes in the pathogenesis of these symptoms, we also performed a cognitive assessment focused on executive functions. The prevalence of the various affective symptoms was as follows:apathy 15.2 %, anhedonia 6.1 %, emotional lability 48.5 %, depression 57.6 % of cases. Patients had a normal global cognitive level (mean short portable mental status questionnaire: 8.4 +/- 1.0, range 7-10). Apathy and anhedonia showed significant reciprocal correlations and they were also correlated with the executive score and the Barthel index;apathy was also correlated with depression; emotional lability, instead, was correlated only with depression. The study of possible anatomo-functional correlates between unconventional affective symptoms and lesion site did not show significant differences (stroke in the right versus left hemisphere, anterior versus posterior and cortical versus subcortical locations).

Assessing clinically relevant cognitive decline: preliminary data on a new method.

Physiological age-related cognitive decline, practice effect and regression to the mean may interfere with the interpretation of psychometric changes between subsequent neuropsychological evaluations. The standardized regression-based (SRB) change score allows investigators to define clinically relevant cognitive change on an individual basis controlling for these confounding factors. We performed a preliminary study to test its applicability and usefulness in the neuropsychological diagnosis of dementia. We derived a regression equation for the tests of a widely used Italian battery for global cognitive assessment, the Mental Deterioration Battery, in a sample of 20 normal elderly and we tested the potential clinical application of the SRB methodology in two cases of questionable dementia.

Cognitive [correction of cognitve] estimation: comparison of two tests in nondemented parkinsonian patients.

The Time and Weight Estimation test (STEP) and the Cognitive Estimation Task (CET) are two recently devised tests for the assessment of cognitive estimation. In the present study, we compared their performance in 30 non-demented idiopathic parkinsonian (PD) patients, also evaluated with the Frontal Assessment Battery (FAB) as an index of executive impairment, with the aim of verifying the putative frontal circuitry of cognitive estimation processes. Six patients (20%) showed a pathological performance on either or both tests. After division of the PD sample into tertiles based on the FAB score, no significant difference was detected by either estimation test. Furthermore, the two questionnaires were unrelated to each other. Thus, deficits of cognitive estimation ability appear to be mild in PD without dementia and do not correlate with executive impairment. Unexpectedly, the CET and the STEP seem to have no unique underlying construct.

Physical anhedonia in Parkinson's disease.

Anhedonia is the inability to experience physical or social pleasure. Its physical component is hypothesised to be due to dysfunction of a dopaminergic frontotemporal-subcortical circuit and has never been investigated as a possible affective complication of Parkinson's disease (PD). The aim of this study was to formally assess prevalence and correlates of physical anhedonia in PD patients compared with normal controls. Twenty five people with PD and 25 matched controls were administered a psychometric battery exploring mainly executive functions and mood. Hedonic tone was assessed using Chapman's Physical Anhedonia Scale. PD patients also underwent MRI linear measurement of frontal structures. Anhedonia levels were significantly higher in PD patients with respect to controls, although not extremely elevated; prevalence rate was 40% for parkinsonians, while no anhedonics were found among controls. Clinical, neuropsychological, and quantitative neuroradiological features did not show any significant correlation with physical anhedonia. Physical anhedonia appears to be a relatively frequent, although mild, affective disturbance of PD, independent from neurological, frontal, and depressive aspects.

Screening cognitive decline in dementia: preliminary data on the Italian version of the IQCODE.

The IQCODE is a retrospective questionnaire for caregivers about changes which occurred in a patient's cognitive and functional efficiency in the previous 10 years of life. Previous studies demonstrated the validity of the IQCODE for the screening of dementia similar to that of traditional cognitive screening tests, with the additional advantage of allowing the detection of cognitive change, rather than just cognitive impairment. The present paper deals with the preliminary results of the validation of the Italian version of the questionnaire in a sample of 45 mild to severely demented patients and 13 patients with mild cognitive impairment (MCI), compared to 20 cognitively intact elderly subjects. The IQCODE demonstrated satisfactory discriminative power for dementia as well as for MCI and a good correlation with the MMSE.