[Show abstract][Hide abstract] ABSTRACT: When copying or recalling a figure from memory, some patient with dementia or focal brain lesions may rotate the drawing through ±90° or 180°. We have tried to clarify the nature of this phenomenon by investigating the cognitive profile of 22 patients who rotated the copy of the Rey–Osterrieth Complex Figure and 27 who rotated (only) the recall, and two control groups of cases with the same neuropsychiatric diagnoses, but no misorientation deficit. Brain MRI and FDG-PET images were also analysed. Predictor of rotation at the copy versus rotation at the recall was visuospatial impairment as measured by the copy of the Rey Figure; predictors of rotation at the copy versus no rotation were, again, visuospatial deficits, in addition to an abnormal performance at the task of selective attention. No specific profile of cognitive impairment distinguished patients with and without rotation at the recall. Disproportionate temporo-parieto-occipital atrophy or hypometabolism were evident in cases with misorientation of the copy, while predominant frontal abnormalities were found in cases of rotated recall. Based on these findings, rotated drawing at the copy is interpreted as a dorsal visual stream deficit, whose occurrence is more probable when attentional control is impaired. Rotation at recall seems to have a distinct, more anterior, neural substrate, but its dysexecutive nature has yet to be demonstrated.
Brain and Cognition 01/2014; 85:286–290. · 2.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rotation of drawings has been described in focal brain lesions, at copy when the dorsal visual stream is involved, at recall in patients with memory or frontal dysfunction. In the present study Rey-Osterrieth Complex Figure performance was reviewed in 445 consecutive patients with mild cognitive impairment or degenerative dementia; a smaller sample (n = 243) had also performed the recall trial. Rotation was present in 19 cases overall: at copy in 11, at recall in 7, and at recall on a first assessment and at copy on retest in 1 last patient. Rotation at copy was often associated with neuropsychological and metabolic imaging evidence of parietal dysfunction, supporting previous evidence that rotation at copy might be due to an impairment of object perception processes within the dorsal visual stream. Rotation at recall seemed to be related predominantly to executive deficits, but no specific hypothesis on its cognitive origin can be advanced based on the present data.
The Clinical Neuropsychologist 10/2013; · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Parkinsonism & Related Disorders 09/2013; · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Parkinsonism & Related Disorders 08/2013; · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: While it is well accepted that the left prefrontal cortex plays a critical role in planning and problem-solving tasks, very little is known about the role of the right prefrontal cortex. We addressed this issue by testing five neurological patients with focal lesions to right prefrontal cortex on a real-world travel planning task, and compared their performance with the performance of five neurological patients with focal lesions to left prefrontal cortex, five neurological patients with posterior lesions, and five normal controls. Only patients with lesions to right prefrontal cortex generated substandard solutions compared to normal controls. Examination of the underlying cognitive processes and strategies revealed that patients with lesions to right prefrontal cortex approached the task at an excessively precise, concrete level compared to normal controls, and very early locked themselves into substandard solutions relative to the comparison group. In contrast, the behavior of normal controls was characterized by a judicious interplay of concrete and abstract levels/modes of representations. We suggest that damage to the right prefrontal system impairs the encoding and processing of more abstract and vague representations that facilitate lateral transformations, resulting in premature commitment to precise concrete patterns, and hasty albeit substandard conclusions (because the space of possibilities has not been properly explored).
[Show abstract][Hide abstract] ABSTRACT: The "applause sign" is a motor perseveration described in focal and neurodegenerative disorders and characterized by fronto-subcortical dysfunction. Most previous formal investigations focused on Parkinson's disease or progressive supranuclear palsy. We assessed the prevalence of the applause sign in patients affected by Alzheimer's disease (AD), Lewy body dementia (LBD), corticobasal syndrome (CBS), and posterior cortical atrophy (PCA), with the aim to verify its contribution to the differential diagnosis. We enrolled 20 patients with AD, 20 with LBD, 16 with CBS, and ten with PCA, and 30 healthy controls. The three clap test (TCT) was used to elicit the applause sign, and was scored by raters blinded to the diagnosis. Correlation with motor (extrapyramidal) and cognitive measures was also performed. A maximum 40 % prevalence of a positive applause sign was found in the two parkinsonian syndromes, which could be discriminated from the two cortical groups with a positive predictive value of 82 % and a negative predictive value of 55 %. According to our findings, a diagnosis of LBD or CBS, rather than of AD or PCA, is highly probable in the presence of an abnormal TCP, but cannot be ruled out based on a negative result. No relevant correlates emerged that could clarify the origin and nature of the applause sign.
Journal of Neurology 12/2012; · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the possible involvement of vascular damage in the pathogenesis of Alzheimer's disease (AD), by assessment of plasma levels of tissue factor pathway inhibitor (TFPI), a serine protease inhibitor induced by endothelial injury, and homocysteine (Hcy), a known risk factor for cerebrovascular disorders, folate levels were also measured. 110 probable AD, 38 mild cognitive impairment, 31 patients affected by idiopathic Parkinson's disease (without dementia) and 100 healthy controls, who displayed no vascular disorders were enrolled. TFPI and Hcy were significantly higher in AD patients with respect to other groups. The levels of TFPI and Hcy were positively correlated in hyperhomocysteinemic AD and mild cognitive impairment subjects, and were negatively correlated with folate levels. Our findings suggest that an impairment of endothelial function associated with high Hcy levels may occur in AD patients, despite the absence of manifest cerebrovascular lesions. Therefore, TFPI may represent a candidate marker of endothelial damage in AD and might be used for the identification and monitoring of patients that would benefit from folate supplementation treatment.
Neurobiology of aging 02/2012; 33(2):226-33. · 5.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with semantic dementia (SD) show deficits in phoneme binding in immediate serial recall: when attempting to reproduce a sequence of words that they no longer fully understand, they show frequent migrations of phonemes between items (e.g., cap, frog recalled as "frap, cog"). This suggests that verbal short-term memory emerges directly from interactions between semantic and phonological systems, allowing semantic knowledge to make a critical contribution to the stability of phonological sequences. According to this standpoint, SD patients should show phoneme binding deficits in additional language tasks beyond standard assessments of verbal short-term memory: for example, these errors should emerge in paced reading, which also requires the rapid production of semantically degraded words in order. To test this hypothesis, we examined a cyclical paced reading task in three SD patients for the first time. Every patient showed deficits in phoneme binding: they were more vulnerable than a set of age-matched controls to phoneme competition effects following the repetition of a small set of words across several cycles. They also showed substantially elevated numbers of phoneme migration, substitution and omission errors, despite being able to read the individual words almost without error. These findings confirm that the semantic contribution to phoneme binding is disrupted in SD patients across tasks. In line with the view that verbal short-term memory emerges from interactions between basic phonological and semantic components, these effects occur both within classic short-term memory paradigms, such as immediate serial recall, and tasks without explicit memory demands, such as paced reading.
[Show abstract][Hide abstract] ABSTRACT: Verbal confabulation (VC) has been described in several pathological conditions characterized by amnesia and has been defined as 'statements that involve distortion of memories'. Here we describe another kind of confabulation (graphic confabulation, GC), evident at the recall of the Rey-Osterrieth complex figure (ROCF). In a retrospective study of 267 patients with mild-to-moderate dementia, 14 patients (4.9 %) recalled the abstract ROCF as drawings with recognizable semantic meaning. VC was evident at the story recall test in 19.8% of the study participants. VC and GC were homogeneously distributed among the different types of dementia. VC has been proposed to originate from complex interactions of amnesia, motivational deficit and dysfunction of monitoring systems. On the contrary, GC seems to be the result of a deficit in visual memory replaced by the semantic translation of isolated parts of the ROCF along with a source monitoring deficit.
Dementia and geriatric cognitive disorders extra. 01/2011; 1(1):372-80.
[Show abstract][Hide abstract] ABSTRACT: Acetyl-cholinesterase inhibitors (AChEI) are drugs frequently prescribed for the treatment of Alzheimer's disease (AD), exerting an effect on cognition, as well as on behavioural and psychological symptoms of dementia and activities of daily living. The efficacy of AChEI may be ascribed not only to the activation of cholinergic transmission, but also to other mechanisms, among which a putative regulation of the immune response has already been hypothesized. In the present study, we evaluated, in a cross-sectional sample of 66AD patients and 48 healthy controls, the putative influence of AChEI on anti-Abeta 1-42 antibody plasma levels by ELISA assay. AD patients receiving AChEI therapy showed increased plasma levels of anti-Abeta 1-42 antibodies respect to untreated AD patients and antibodies levels similar to those of healthy controls, both before and after normalization by total IgG values. Our results support a potential role of AChEI in the modulation of the immune response against Abeta. We suggest that a strategy aimed at increasing the endogenous response against this peptide might represent an interesting therapeutic target to be further investigated.
[Show abstract][Hide abstract] ABSTRACT: Alzheimer disease (AD) is the most prevalent neurodegenerative disease, characterized by an increased deposition of β-amyloid (Abeta) within the central nervous system, leading to neuronal death. The availability of effective models, in which confirming novel pathogenic hypotheses and developing therapeutic targets, represents a very important goal for the field of AD. Fibroblasts from these patients may be relevant models in which addressing these issues, as they display biochemical alterations mirroring SNC ones. In this work, fibroblasts obtained from controls were studied after exposure to nonfibrillar Abeta 1-42, showing decreased glutamate uptake, similar to that observed in AD cells, in absence of transporters modifications. Nonfibrillar Abeta 1-42 was able to induce in control cells mitochondrial alterations and p38-phosphorylation, mirroring similar alterations found in AD fibroblasts. Under our experimental conditions, this treatment induced neither apoptosis nor necrosis. To investigate a putative role of p38-modulation in mediating nonfibrillar Abeta 1-42 toxicity, fibroblasts from controls were pretreated with retinoic-acid, and SB203580, a p38-inhibitor. These pretreatments prevented both p38-phosphorylation and glutamate uptake inhibition. Our results suggest that nonfibrillar Abeta 1-42 downregulates glutamate transporters activity interfering with p38-activation and mitochondrial stress. Thus, modulating complex kinase signaling pathway might represent a future therapeutic target in AD.
[Show abstract][Hide abstract] ABSTRACT: 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.
data were collected with an analytical form that was developed by an expertise of neurologists.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: To identify the real number of hyperhomocysteinemic Alzheimer's patients who may benefit from homocysteine-lowering therapy.
Basal and post-methionine load homocysteine levels were assessed by rp-HPLC system.
PML test revealed twice as many hyperhomocysteinemic AD subjects with respect to the fasting analysis.
PML test resulted useful in detecting higher number of hyperhomocysteinemic AD patients who may have the chance of an early folate treatment.
[Show abstract][Hide abstract] ABSTRACT: The "frontal aging hypothesis" predicts that brain senescence affects predominantly the prefrontal regions. Preliminary evidence has recently been gathered in favour of an age-related change in a typically frontal process, i.e. decision making, using the Iowa Gambling Task (IGT), but overall findings have been conflicting. Following the traditional scoring method, coupled with a qualitative analysis, in the present study we compared IGT performance of 40 young (mean age: 27.9+/-4.7) and 40 old (mean age: 65.4+/-8.6) healthy adults and of 18 patients affected by frontal lobe dementia of mild severity (mean age: 65.1+/-7.4, mean MMSE score: 24.1+/-3.9). Quantitative findings support the notion that decision making ability declines with age; moreover, it approximates the impairment observed in executive dysfunction due to neurodegeneration. Results of the qualitative analysis did not reach statistical significance for the motivational and learning decision making components considered, but approached significance for the attentional component for elderly versus young normals, suggesting a possible decrease in the ability to maintain sustained attention during complex and prolonged tasks as the putative deficit underlying impaired decision making in normal aging.
[Show abstract][Hide abstract] ABSTRACT: In this study we investigated two patients with pure alexia, F.C. and L.D.S., in order to make inferences about how processes and levels involved in the early stage of visual word recognition are organized and how they can be selectively damaged. Moreover, we investigated whether pure alexia can be caused by different functional deficits. F.C. and L.D.S. were presented with tasks of letter processing and tasks of orthographic integration. There was a clear double dissociation between the pattern of performance of F.C. and L.D.S. F.C. was able to process single letters rapidly and accurately, but was unable to group together the letters that he had correctly identified. By contrast, L.D.S. was slower and more impaired at letter identification, but she could use letter groups to assist reading. Thus, two different forms of pure alexia emerged: F.C. has a higher level deficit in integrating letters, whereas L.D.S. has a lower level deficit in letter processing. The results support the assumption of a functional organization of the reading process that involves a series of orthographic units (i.e., single letters, sublexical letter groups, and the lexical unit), which can be selectively damaged. Finally, our data present difficulties for models of pure alexia that assume all patients to have a low-level processing deficit.