Emanuela Onofri

Altered Cytokine and BDNF Levels in Autism Spectrum Disorder

The contribution of neuroimmune functioning and brain-derived neurotrophic factor (BDNF) to functional dysregulation in autism spectrum disorder was assessed in 29 patients under treatment in two specialized centers of Basilicata (Chiaromonte and Matera), Southern Italy, through analysis of serum levels of cytokines and BDNF. Elevated levels of the pro-inflammatory cytokine, including interleukin-1, interleukin-6, interleukin-12, interleukin-23, tumor necrosis factor-α and BDNF were observed, regardless of age and gender. Comparisons were made with age- and gender-related healthy controls. The present findings reinforce current notions regarding immunoexcitotoxic mechanisms contributing to the pathophysiology of autistic disorder.

Cognitive Performance Deficits and Dysgraphia in Alzheimers DiseasePatients

Introduction: Agraphia or dysgraphia, observed often in early AD, encompasses a progressive disorganization and degeneration of the various components of handwriting. Methods: Deficits in writing ability, dysgraphia, and the relationship with other measures of cognitive decline were studied in a group of 30 patients, originating from the Lazio region, Rome, Italy, presenting a moderate to relatively severe stage of Alzheimer’s disease (AD). Extent of dysgraphia and cognitive performance was compared with a matched group of healthy controls selected from the same region. Results: Several markedly strong relationships between dysgraphia and several measures of cognitive performance in AD patients were observed concomitant with consistent deficits by this patient sample in comparison with the matched group of healthy control subjects were obtained. Additionally, several measures of loss of functional integrity, MMSE, ADL and IADL, were found to be associated with both dysgraphia and impairments in cognitive performance. Conclusions: The present results are discussed from the notion of affected brain regions underlying functions in cognition, language and motor domains that are disturbed in AD. Marked relationships between dysgraphia and several measures of cognitive performance in AD patients were observed concomitant with consistent deficits by this sample in comparison with a matched group of healthy control subjects.

Cognitive fluctuations in connection to dysgraphia: a comparison of Alzheimer’s disease with dementia Lewy bodies

Background The purpose of the present study was to examine the relationship between cognitive impairment and the performance of handwritten scripts presented as “letter-writing” to a close relative by patients with dementia Lewy bodies (DLB), as fluctuations of the symptoms phase, and in a matched group of patients with Alzheimer’s disease (AD). The degree of writing disability and personal, spatial, and temporal orientation was compared in these two groups. Design and methods Fourteen simple questions, designed in a form that could be utilized by any general practitioner in order to document the level of cognitive functioning of each patient, were presented to 30 AD patients and 26 DLB patients. The initial cognition test was designated PQ1. The patients were examined on tests of letter-writing ability. Directly after the letter-writing, the list of 14 questions presented in PQ1 was presented again in a repeated procedure that was designated PQ2. The difference between these two measures (PQ1 – PQ2) was designated DΔ. This test of letter-writing ability and cognitive performance was administered over 19 days. Results Several markedly strong relationships between dysgraphia and several measures of cognitive performance in AD patients and DLB patients were observed, but the deterioration of performance from PQ1 to PQ2 over all test days were markedly significant in AD patients and not significant in DLB patients. It is possible that in graphic expression even by patients diagnosed with moderate to relatively severe AD and DLB there remains some residual capacity for understanding and intention that may be expressed. Furthermore, the deterioration in performance and the differences noted in AD and DLB patients may be due to the different speed at which the process of the protein degradation occurs for functional modification of synapses. Conclusion Our method can be used as part of neuropsychological tests to differentiate the diagnosis between AD and DLB.

Dysgraphia in Relation to Cognitive Performance in Patients with Alzheimer's Disease

Dysgraphia has been observed in patients presenting mild to moderate levels of Alzheimer’s disease (AD) in several studies. In the present study, 30 AD patients and 30 matched healthy controls, originating from the Lazio region, Rome, Italy, were examined on tests of letter-writing ability and cognitive performance over a series of 10 test days that extended over 19 days (Test days: 1, 3, 5, 7, 9 11, 13, 15, 17, and 19). Consistent deficits by the AD patients over the initial cognition test (PQ1), 2 nd cognition test (PQ2) and the difference between them (D∆), expressing deterioration, and writing-time compared the group of healthy control subjects were obtained. Furthermore, the performances of the AD patients on the PQ1, D∆ and writing-time, but not the PQ2, tests deteriorated from the 1 st five days of testing (Days 1-9) to the 2 nd five days (11-19). Both AD patients’ and healthy controls’ MMSE scores were markedly and significantly correlated with performance of PQ1, writing-time and PQ2. The extent of dysgraphia and progressive deficits in the AD patients implicate multiple brain regions in the loss of functional integrity.

Quality of life in dementia sufferers: diet and exercise in an evaluatory role.

BACKGROUND Among the myriad of factors modulating quality of life assessments estimated in patients presenting a variety of cognitive impairments, the distinctive and critical influence of diet and exercise cannot be overestimated. OBJECTIVE The objective of this study was to review the evidence to confirm the association between these health-endowering agents and cognitive performance in People With Dementia as well as providing a correlation between Mini Mental State Examination scores and available anthropometric data. METHODS The authors tested the hypothesized correlation on a sample of subjects with instrumentally confirmed cognitive impairment using parameters as Body Mass Index and calf circumference. RESULTS The results confirm the hypothesis and suggesting the possible use of anthropometric data in the process of objective evaluation of the patient with cognitive impairment that could also be used for forensic medicine.

Legal medical consideration of Alzheimer’s disease patients’ dysgraphia and cognitive dysfunction a 6 month follow up

Background The purpose of this study was to investigate the ability of Alzheimer’s disease (AD) patients to express intentions and desires, and their decision-making capacity. This study examines the findings from a 6-month follow-up of our previous results in which 30 patients participated. Materials and methods The patient’s cognition was examined by conducting the tests of 14 questions and letter-writing ability over a period of 19 days, and it was repeated after 6 months. The difference between these two cognitive measures (PQ1 before–PQ2 before), tested previously and later the writing test, was designated DΔ before. The test was repeated after 6 months, and PQ1 after–PQ2 after was designated DΔ after. Results Several markedly strong relationships between dysgraphia and other measures of cognitive performance in AD patients were observed. The most aged patients (over 86 years), despite less frequency, maintain the cognitive capacity manifested in the graphic expressions. A document, written by an AD patient presents an honest expression of the patient’s intention if that document is legible, clear, and comprehensive. Conclusion The identification of impairment/deficits in writing and cognition during different phases of AD may facilitate the understanding of disease progression and identify the occasions during which the patient may be considered sufficiently lucid to make decisions.

Altered levels of IL-18 in sera of autism patients as well as in reeler brain

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with onset in the first 3 years of life, with an incidence in Italy of 6–10 new cases per 10,000 children per year. Affected children show impaired social interactions, repetitive or stereotypical behaviors and interests. Disruption/dysregulation of neuroimmune functioning, whether expressed in the patient or during the course of the individual’s brain development, are implicated in Idiopathic ASD (1). Quantitative and qualitative differences in immune function between children with ASD and typically developing controls have been demonstrated, including evidence for increased neuroinflammation and cytokine production in brain specimens obtained from individuals with ASD(2). Peripheral innate immune activation is starting to be recognized as a prominent feature of diseases affecting the central nervous system.(3) In a recent study we have shown that elevated levels of the pro-inflammatory cytokines including interleukin-1, interleukin-6, interleukin-12, interleukin-23, tumor necrosis factor-alpha and BDNF were present in sera of autistic patients (4).We have recently observed that the levels of IL-18 detected in the sera of autistic children were rather lower than those measured in the sera of matched healthy children. We decided to inquire if an alteration in the amount of IL-18 in different areas of the CNS and in the serum was also detectable in Reeler eterozygous mice, a mouse model of autism, compared to wild type mice. IL-18 was localized in different brain regions by immunohistochemistry and in whole brain homogenates by western blots. Quantitative analysis of the cytokine in serum was performed by ELISA.