Micaela Sepe-Monti

Clinical findings, functional abilities and caregiver distress in the early stage of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD)

Few studies have compared neuropsychiatric disorders and functional abilities in the early stage of DLB and AD and their influence on caregiver distress. The aim of this study is to assess neuropsychiatric disorders, functional abilities and caregiver distress in DLB and in AD subjects. Sixteen subjects affected by probable DLB and 12 subjects affected by probable AD were enrolled. All subjects underwent a wide neuropsychological examination. Caregivers distress was also assessed. Subjects affected by DLB performed better in long-term memory tests, whereas AD subjects performed better in attentive and executive function tests. The Neuropsychiatric Inventory (NPI) total score was significantly higher in DLB subjects than in AD subjects. Furthermore, DLB subjects scored worse than AD subjects in both Activities of Daily Living scale (ADL) and Instrumental Activities of Daily Living scale (IADL) scales. Overall caregiver distress was higher in DLB than in AD subjects. High distress was observed in DLB caregivers alone and was caused by delusion, hallucinations, anxiety and apathy. DLB subjects have a different neuropsychological profile, more psychiatric symptoms and more serious functional deficits than AD subjects in the early cognitive decline, furthermore DLB caregivers are more stressed than AD caregivers.

Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis

Objectives – The present study was planned to investigate the relationship between the plasma lipid profile and disease activity in patients with a first clinical episode suggestive of multiple sclerosis (MS). Material and methods – Eighteen consecutive out‐patients underwent a monthly brain magnetic resonance imaging (MRI), blood sample and neurological assessment over 6 months. Blood samples were used to evaluate total cholesterol and triglyceride levels as well as their lipoprotein fractions. Plasma total apolipoprotein E concentration was also determined. Results – We found a significant correlation between the mean number of enhancing lesions and the mean plasma level of both total and low density lipoprotein cholesterol. The total plasma cholesterol level increased on average by 4.4 mg/dl for each enhancing lesion. Conclusion – Our preliminary data suggest a potential role of plasma cholesterol level as a biological marker of disease activity after a first demyelinating event. Further studies need, however, to be designed to determine whether the plasma cholesterol level is of practical use in monitoring the disease course.

Heritability of neurocognitive functioning in the elderly: evidence from an Italian twin study

BACKGROUND the genetic and environmental origins of individual differences in specific cognitive abilities in the elderly are poorly understood. One reason is the lack of studies performed in cohorts with normal cognitive functions. OBJECTIVE to estimate the relative contributions of genetic and environmental factors in determining inter-individual variation in neurocognitive abilities in the Italian population. DESIGN cross-sectional analysis of twin data. SETTING a sample of older twins with normal cognition from the population-based Italian Twin Registry (ITR). SUBJECTS twin pairs resident in Rome and born between 1926 and 1940, identified through the ITR in 2002. The final study population included 93 twin pairs. METHODS subjects underwent neuropsychological tests providing information about different cognitive domains. The contributions of genetic and environmental effects were assessed using standard univariate twin modelling based on linear structural equations. RESULTS the best-fitting model incorporated additive genetic (A) and unique environmental (E) sources of variance for the following tests: Mini-Mental State Examination (A = 55%), Raven (A = 56%), Attentional Matrices (A = 79%), Copying Drawings (A = 69%) and Story Recall (A = 54%). For Phonological and Semantic Verbal Fluency, the best model included non-additive (D) and unique environmental influences (D = 62 and 54%, respectively). Cigarette smoking was estimated to be negatively associated with the score of Phonological Verbal Fluency. For Token test, the inter-individual variance was entirely due to environmental factors not shared by the twins. CONCLUSION our data showed that most of the specific cognitive abilities are moderately to highly heritable, and that the environmental factors of relevance for these abilities are those causing within-family differences.

Vascular risk factors and white matter hyperintensities in patients with amnestic mild cognitive impairment

Background –  Subjects affected by aMCI are considered at high risk for AD. Nevertheless, the role of both vascular risk factors and WMH is matter of debate.

T cell response to amyloid-β and to mitochondrial antigens in Alzheimer's disease

Despite the vast amount of literature on non-specific immune mechanisms in Alzheimer’s disease (AD), little is known about the role of antigen-specific immune responses. We investigated T cell reactivity to fragment 1–42 of amyloid-β (Aβ) and to N-terminal peptides of human mitochondrial and control microbial proteins. Thirty subjects with a diagnosis of probable AD according to NINCDS-ADRDA criteria and 30 sex- and age-matched healthy controls were enrolled. T cell responses to Aβ fragment showed no significant differences between AD patients and controls. By contrast, the mean number of positive T cell responses to both human mitochondrial and microbial peptides was significantly decreased in AD patients compared to control subjects. No significant correlation was found between T cell responses and both the severity of cognitive impairment and duration of the disease. Our results suggest that antigen-specific immune responses are impaired in AD. Protective immune responses to harmful amyloidogenic substances may also be impaired, thus favoring their accumulation in the brain.

Increased Lymphocyte Dopamine β-Hydroxylase Immunoreactivity in Alzheimer’s Disease: Compensatory Response to Cholinergic Deficit?

There is growing interest in the characterization of peripheral blood lymphocytes (PBL) as a biological tool with which to investigate changes in the neurotransmitter-receptor system in neurodegenerative disorders. Here we show a slight decrease in acetylcholinesterase (AChE) and a significant increase in dopamine β-hydroxylase (DBH) immunoreactivity in the PBL of patients with probable Alzheimer’s disease (AD). Therapy with AChE inhibitors completely reversed the increase in DBH immunoreactivity. We hypothesize that the increase in DBH immunoreactivity may represent a compensatory response to cholinergic impairment. Our findings suggest that neurochemical interactions between the noradrenergic and cholinergic systems may be measured at a peripheral level in AD.

Anosognosia in People with Cognitive Impairment: Association with Cognitive Deficits and Behavioral Disturbances

Aims: To investigate, in a group of subjects at an early stage of cognitive impairment, the relationship between anosognosia and both cognitive and behavioral symptoms by exploring the various domains of insight. Methods: One hundred and eight subjects affected by cognitive impairment were consecutively enrolled. The level of awareness was evaluated by means of the Clinical Insight Rating Scale (CIRS). Psychiatric symptoms were evaluated using the Italian version of the Neuropsychiatric Inventory (NPI), whereas memory (memory index, MI) and executive (executive index, EI) functions were explored using a battery of neuropsychological tests and qualified by means of a single composite cognitive index score for each function. Results: A significant positive correlation between the total NPI score and global anosognosia score was found. Furthermore, both the MI and EI scores were lower in subjects with anosognosia than in those without anosognosia (p < 0.001 and p < 0.007, respectively). When the single domains of the CIRS were considered, anosognosia of reason of visit correlated with the EI score (r = -0.327, p = 0.01) and night-time behavioral disturbances (r = 0.225; p = 0.021); anosognosia of cognitive deficit correlated with depression (r = -0.193; p = 0.049) and the MI score (r = -0.201; p = 0.040); anosognosia of functional deficit correlated with the MI score (r = -0.257; p = 0.008), delusions (r = 0.232; p = 0.015) and aberrant motor behavior (r = 0.289; p = 0.003); anosognosia of disease progression correlated with the MI score (r = -0.236; p = 0.015), agitation (r = 0.247; p = 0.011), aberrant motor behavior (r = 0.351; p = 0.001) and night-time behavioral disturbances (r = 0.216; p = 0.027). Conclusions: Our study suggests that, in the early stage of cognitive impairment, anosognosia is associated with both cognitive deficits and behavioral disorders according to the specific functional anatomy of the symptoms.

MRI evidence of bilateral hippocampal sclerosis in amnestic mild cognitive impairment.

We present the case of a man affected by amnestic mild cognitive impairment (aMCI) who showed bilateral hippocampal sclerosis at magnetic resonance imaging (MRI). We argue the concept that aMCI is heterogeneous syndrome and suggested the utility of coronal T2‐weighted MRI images in the routine dementia workup.

Neuropsychological Patterns Underlying Anosognosia in People with Cognitive Impairment

Aims: To investigate, in a group of subjects with cognitive impairment, the relationship between anosognosia, in each dimension of insight, and neuropsychological domains. Methods: Two hundred and seventy-one subjects affected by cognitive impairment were consecutively enrolled. Anosognosia was evaluated by means of the Clinical Insight Rating Scale (CIRS). The general level of cognitive impairment was evaluated by means of the Mini-Mental State Examination, while 8 cognitive domains were examined by means of neuropsychological tests. Results: The number of subjects with anosognosia evaluated by means of the CIRS total score as well as those with anosognosia divided according to the reason for visit was higher in moderately cognitively impaired subjects than in mildly cognitively impaired subjects (p < 0.001). A relationship between anosognosia and neuropsychological scores was only found in mild cognitive impairment, with subjects with anosognosia displaying significantly lower Raven’s Colored Progressive Matrices Test and Rey Auditory Verbal Learning Test-delayed recall scores than subjects without anosognosia. Conclusions: Our study suggests that the relationship between the severity of cognitive deficits and anosognosia in subjects with cognitive impairment is partial and depends on the specific domain of unawareness. Furthermore, in the early phase of cognitive impairment, the presence of specific cognitive deficits suggests that the nature of anosognosia is domain-specific.

Erectile dysfunction in myotonic dystrophy type 1 (DM1)

JO N 2912 and personal life of these patients. Hypothesizing that impotence may be an intrinsic characteristic in DM1, we performed a study to assess its frequency and characteristics. The complete series of male patients (aged 18-60 years) with genetically-confirmed DM1, under clinical surveillance in our Neuromuscular Unit in January 2005, was clinically evaluated for any disease or medication and tested with both the Mini-Mental State Examination and Hamilton Depression Rating Scale. Subjects with physical or mental diseases known to interfere with sexual activity [4] and those with congenital DM1, or cognitive dysfunction or HAM-D “severe” or “very severe” scores, were excluded. Patients are shown in Fig. 1. A total of 31 patients and 31 age-matched healthy controls filled out the questionnaire of the Internationally Validated Index of ErecGiovanni Antonini Alessandro Clemenzi Elisabetta Bucci Stefania Morino Matteo Garibaldi Micaela Sepe-Monti Franco Giubilei Giuseppe Novelli