Elisabetta Cottini

Prevalence and pattern of cognitive impairment in systemic lupus erythematosus patients with and without overt neuropsychiatric manifestations

The prevalence and pattern of cognitive impairment in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (nSLE) overt neuropsychiatric manifestations were investigated. Fifty-two nSLE patients, 23 NPSLE patients and 27 healthy controls were evaluated with a battery of standardized neuropsychological and psychological tests. Disease duration, disease activity index, and current corticosteroid therapy were collected. Cognitive impairment was identified in 14 (26.9%) and in 12 (52.2%) of subjects with nSLE and NPSLE, respectively. Both SLE groups showed a significant impairment compared with controls on tasks assessing verbal and non-verbal long-term memory, and visuoconstructional abilities. In addition, NPSLE patients reported worse performances than both nSLE patients and controls on task evaluating short-term visuospatial memory. NPSLE subjects were significantly more anxious and depressed compared to both nSLE subjects and controls. By multivariate analysis, only depression levels, among clinical variables, significantly predicted cognitive performance. This study shows that cognitive impairment occurs frequently in both nSLE and NPSLE subjects. The higher frequency in NPSLE may be related to coexisting depressive disturbances.

Amyloid precursor protein in platelets A peripheral marker for the diagnosis of sporadic AD

Background: An altered pattern of amyloid precursor protein (APP) forms consisting in a reduced ratio between the upper (130 kDa) and the lower (106 to 110 kDa) immunoreactivity bands has been described in platelets of patients with AD. Objective: To evaluate the sensitivity and the specificity of platelet APP forms’ ratio (APPr) as a marker for AD. Methods: Eighty-five patients with probable AD and 95 control subjects (CON), including healthy individuals and neurologic patients, entered the study. Platelet APPr was evaluated by means of Western Blot analysis and immunostaining in the whole platelet homogenate, and calculated by the ratio between the optical density (OD) of the upper (130 kDa) and the lower (106 to 110 kDa) APP immunoreactive bands. Results: Mean APPr levels were decreased in AD patients (mean OD ± SD = 0.35 ± 0.18) compared with the CON group (mean OD ± SD = 0.92 ± 0.38) (DF 1, 178, p < 0.0001). Accuracy levels measured by Receiver Operating Curve analysis showed that a cut-off level of 0.57 resulted in a sensitivity of 88.2% and a specificity of 89.4%, with an area under the curve of 0.945. APPr levels were significantly associated with disease severity (mild AD versus moderate AD: p < 0.0001; moderate AD versus severe AD: p < 0.05). Conclusion: Platelet APPr allowed to differentiate AD from normal aging and other dementing disorders with high sensitivity and specificity. These findings suggest that platelet APPr may be of help as an adjunctive diagnostic tool in clinical practice.

Is transient global amnesia a risk factor for amnestic mild cognitive impairment

Abstract.Transient Global Amnesia (TGA) is a common condition of unknown aetiology characterised by the abrupt onset of severe anterograde amnesia, which lasts less than 24 hours. Some authors have suggested that subclinical impairment of memory functions may persist for much longer, but neuropsychological assessment lasting years after TGA attack has not been performed so far. The aim of this study was to evaluate longterm cognitive functions in patients with a previous TGA episode. Fifty-five patients underwent a standardised neuropsychological assessment after at least one-year from the TGA attack, and were compared with 80 age-matched controls. TGA patients showed worse performances on tests evaluating verbal and nonverbal long-term memory and attention, with comparable global cognitive functions. By applying current criteria for amnestic Mild Cognitive Impairment (MCI-a) on TGA subjects, a group consisting of 18/55 (32.7%) MCI-a subjects was identified. There was no association between the presence of MCIa and demographic variables, vascular risk factors, years since the TGA episode, or ApoE genotype. This study demonstrates that TGA appears to be a relatively benign syndrome although objective memory deficits fulfilling MCI-a criteria persist over time, as detected by multidimensional neuropsychological tasks performed at long-term follow-up.

Structural and functional imaging study in dementia with Lewy bodies and Parkinson's disease dementia

INTRODUCTION Dementia with Lewy Bodies (DLB) and Parkinsons disease with Dementia (PDD) are neurodegenerative disorders with complex clinical picture (parkinsonism, cognitive decline and neuropsychiatric disturbances). The conundrum of whether DLB and PDD represent the same or different entities is still under debate. Advanced neuroimaging techniques may represent a point of view to assess brain correlates in DLB and PDD. The study aimed at evaluating whether DLB and PDD may be labelled under the same disease entity or be considered distinctive pathologies. We compared DLB and PDD patients by assessing structural and functional brain imaging and including PD patients. METHODS Patients with diagnosis of PD, PDD, DLB and a group of healthy controls for neuroimaging comparisons were recruited and changes in structural and resting-state functional MR (Regional Homogeneity, ReHo) were studied. RESULTS No significant atrophy in VBM analysis was evident in PD. Conversely, PDD showed a significant bilateral frontal atrophy, whereas DLB was characterized by a predominant parietal, occipital atrophy; a similar involvement of subcortical regions in PDD and DLB was observed. ReHo demonstrated reduced local coherence of frontal regions in PD and in PDD, whereas DLB patients presented a reduced local connectivity in posterior regions. CONCLUSION Different brain areas are specifically involved in PDD and DLB. In the former group, greater atrophy of frontal regions with concomitant functional connectivity impairment was evident; conversely, structural and functional damage in the posterior regions characterized DLB. Despite an overlapping clinical spectrum, DLB and PDD have different networks involved and different underlying pathogenic pathways.

Is mild vascular cognitive impairment reversible? Evidence from a study on the effect of carotid endarterectomy

Abstract Mild vascular cognitive impairment (mVCI) is a broader term that is intended to detect cognitive loss before the development of dementia. The identification of preventable risk factors as well as therapeutic strategies of intervention is still unclear. It has been suggested that carotid endarterectomy (CEA) improves cognitive functions, beyond the well-known preventive effect upon future stroke events. In the present study, we evaluated the beneficial effect of CEA in restoring mVCI. Among a large sample of subjects, who underwent CEA for severe carotid stenosis, two groups were identified according to the absence (CON) or the presence of cognitive impairment (mVCI). A multidimensional neuropsychological and behavioural assessment was performed in the week prior, and at a 3-month follow-up after CEA. The incidence of mVCI in this sample was 38%. Seventy-eight patients completed the follow-up (48 CON, 30 mVCI). Both groups showed a clinical improvement after CEA, although the effect was significantly higher in the mVCI group in regard to verbal memory (short story, p < 0.05), and attention (digit span, p < 0.05) scores. At follow-up, 60% of mVCI subjects were classified as having normal cognitive functions. Index of disease severity and peripheral arterial disease were found to be the predictors of improvement. These findings support that mVCI represents a heterogeneous, in some cases reversible condition. CEA might be considered a therapeutic option to treat and prevent cognitive decline in mVCI patients.

Platelet amyloid precursor protein forms in AD : a peripheral diagnostic tool and a pharmacological target

Alzheimer Disease (AD) is characterized by the progressive deposition of beta-amyloid in the parenchyma and cerebral microvasculature. The beta-amyloid peptide derives from the metabolism of a larger precursor, Amyloid Precursor Protein (APP). This protein is present in central nervous system, but it is also expressed in peripheral tissues such as circulating cells. An alteration of the APP forms pattern in platelets has been recently reported in AD patients when compared to platelets both of control subjects or non AD patients (NADD). The accuracy of the assay to identify AD is high and decreased levels are found throughout the course of AD with a significant association with severity of symptoms. Moreover, a recent study has demonstrated that AD patients on donepezil (5 mg daily) for 4 weeks displayed two-fold increase in their APPr baseline levels up to normal range. Thus, platelet APP ratio (APPr) holds the potential to be a clinical marker, which might be of helpful and adjunctive value in the diagnosis of AD and in tracking the course of illness, also in the early stages when pharmacological treatment has the greatest potential of being effective.

Vascular Risk Factors and Cognition in Parkinson’s Disease

Vascular risk factors have been associated with cognitive deficits and incident dementia in the general population, but their role on cognitive dysfunction in Parkinsons disease (PD) is still unclear. The present study addresses the single and cumulative effect of vascular risk factors on cognition in PD patients, taking clinical confounders into account. Standardized neuropsychological assessment was performed in 238 consecutive PD patients. We evaluated the association of single and cumulative vascular risk factors (smoking, diabetes, hypercholesterolemia, hypertension, and heart disease), with the diagnosis of PD normal cognition (PDNC, n = 94), mild cognitive impairment (PD-MCI, n = 111), and dementia (PDD, n = 33). The association between single neuropsychological tests and vascular risk factors was evaluated with covariance analyses adjusted for age at onset, educational levels, gender, disease duration, and motor performance. Age, educational levels, disease duration, and motor function were significantly different between PDNC, PD-MCI, and PDD. Heart disease was the only vascular factor significantly more prevalent in PDD compared with PDNC in adjusted analyses. Performance of tests assessing executive and attention functions were significantly worse in patients with hypertension, heart disease, and/or diabetes (p <  0.05). Heart disease is associated with dementia in PD, suggesting a potential window of intervention. Vascular risk factors act especially on attention and executive functions in PD. Vascular risk stratification may be useful in order to identify PD patients with a greater risk of developing dementia. These findings need to be verified in longitudinal studies.

Suicide Risk in Frontotemporal Lobe Degeneration: To be Considered, to be Prevented

Suicide is difficult to ascertain in elderly patients, and dementia might represent a risk factor, though predictors of suicide in dementia are still unknown. We report the case of a patient recently diagnosed as having a behavioral variant of frontotemporal lobar degeneration (FTLD), apathetic syndrome, who committed suicide by hanging. His personal and family history was negative for mental disorders; a depressive syndrome was diagnosed 1 year before FTLD diagnosis, and treated unsuccessfully. To the best of our knowledge, no data are available about self-harmful events in FTLD. This case report argues for the urgent need for developing specific tools for the assessment of suicidal ideation among at-risk population.

Source-Based Morphometry Multivariate Approach to Analyze [123I]FP-CIT SPECT Imaging

Purpose[123I]FP-CIT (DaTSCAN®) single-photon emission computed tomography (SPECT) imaging is widely used to study neurodegenerative parkinsonism, by measuring presynaptic dopamine transporter (DAT) in striatal regions. Beyond DAT, [123I]FP-CIT may be considered for other monoaminergic systems, in particular the serotonin transporter (SERT). Independent component analysis (ICA) implemented in source-based morphometry (SBM) could represent an alternative method to explore monoaminergic pathways, studying the relationship among voxels and grouping them into “neurotransmission” networks.ProceduresOne hundred forty-three subjects [84 with Parkinson’s disease (PD) and 59 control individuals (CG)] underwent DATSCAN® imaging. The [123I]FP-CIT binding was evaluated by multivariate SBM approach, as well as by a whole-brain voxel-wise univariate (statistical parametric mapping, SPM) approach.ResultsAs compared to the univariate whole-brain approach (SPM) (only demonstrating striatal [123I]FP-CIT binding reduction in PD group), SBM identified six sources of non-artefactual origin, including basal ganglia and cortical regions as well as brainstem. Among them, three sources (basal ganglia and cortical regions) presented loading scores (as index of [123I]FP-CIT binding) significantly different between PD and CG. Notably, even if not significantly different between PD and CG, the remaining three non-artefactual sources were characterized by a predominant frontal, brainstem, and occipito-temporal involvement.ConclusionThe concept of source blind separation by the application of ICA (as implemented in SBM) represents a feasible approach to be considered in [123I]FP-CIT (DaTSCAN®) SPECT imaging. Taking advantage of this multivariate analysis, specific patterns of variance can be identified (involving either striatal than extrastriatal regions) that could be useful in differentiating neurodegenerative parkinsonisms.