Cecilia Camarda

Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment.

Alzheimers disease (AD) is the most common type of dementia in the elderly. Products of oxidative and nitrosative stress (OS and NS, respectively) accumulate with aging, which is the main risk factor for AD. This provides the basis for the involvement of OS and NS in AD pathogenesis. OS and NS occur in biological systems due to the dysregulation of the redox balance, caused by a deficiency of antioxidants and/or the overproduction of free radicals. Free radical attack against lipids, proteins, sugars and nucleic acids leads to the formation of bioproducts whose detection in fluids and tissues represents the currently available method for assessing oxidative/nitrosative damage. Post-mortem and in-vivo studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment (MCI). In addition to their individual role, biomarkers for OS and NS in AD are associated with altered bioenergetics and amyloid-beta (Abeta) metabolism. In this review we discuss the main results obtained in the field of biomarkers of oxidative/nitrosative stress in AD and MCI in humans, in addition to their potential role as a tool for diagnosis, prognosis and treatment efficacy in AD.

A Systematic Review of Neuropsychiatric Symptoms in Mild Cognitive Impairment

Mild cognitive impairment (MCI) is a clinical concept proposed as an intermediate state between normal aging and dementia. This condition has multiple heterogeneous sources, including clinical presentation, etiology, and prognosis. Recently, the prevalence and associated features of neuropsychiatric symptoms (NPS) in MCI have been described. We systematically searched the PubMed database (last accessed on August 31, 2008) for articles on NPS in MCI. Included articles used strict selection criteria, and outcome variables were extracted in duplicate; of the 27 articles included, 14 (52%) used prospective cohorts. The global prevalence of NPS in MCI ranged from 35% to 85%. The most common behavioral symptoms were depression, anxiety, and irritability. Hospital-based samples reported a higher global prevalence of NPS than population-based studies; this discrepancy probably reflected differences in demographics, study setting, MCI diagnostic criteria, and behavioral instruments used. Prospective studies showed that NPS, particularly depression, may represent risk factors for MCI or predictors for the conversion of MCI to Alzheimers disease (AD). NPS are very prevalent in subjects with MCI, displaying a similar pattern of symptoms compared to dementia and AD. Large cohort studies using standardized MCI criteria and behavioral instruments are required to evaluate the prognostic role of NPS in MCI.

Migraine Mediates the Influence of C677T MTHFR Genotypes on Ischemic Stroke Risk With a Stroke-Subtype Effect

Background and Purpose— The objective was to investigate the role of C677T MTHFR polymorphism in migraine pathogenesis and in the migraine–ischemic stroke pathway. Methods— A first genotype–migraine association study was conducted on 100 patients with migraine with aura (MA), 106 with migraine without aura (MO), and 105 subjects without migraine, which provided evidence in favor of association of the TT677 MTHFR genotype with increased risk of MA compared with both control subjects (OR, 2.48; 95% CI, 1.11 to 5.58) and patients with MO (OR, 2.21; 95% CI, 1.01 to 4.82). Based on these findings, mediational models of the genotype–migraine–stroke pathway were fitted on a group of 106 patients with spontaneous cervical artery dissection, 227 young patients whose ischemic stroke was unrelated to a spontaneous cervical artery dissection (noncervical artery dissection), and 187 control subjects, and a genotype–migraine partial mediation model was selected. Results— Both migraine and the TT genotype were more strongly associated to the subgroup of patients with spontaneous cervical artery dissection (OR, 4.06; 95% CI, 1.63 to 10.02 for MA; OR, 5.45; 95% CI, 3.03 to 9.79 for MO; OR, 2.87; 95% CI, 1.45 to 5.68 for TT genotype) than to the subgroup of patients with noncervical artery dissection ischemic stroke (OR, 2.22; 95% CI, 1.00 to 4.96 for MA; OR, 1.81; 95% CI, 1.02 to 3.22 for TT genotype) as compared with controls. Conclusions— Migraine may act as mediator in the methylenetetrahydrofolate reductase–ischemic stroke pathway with a more prominent effect in the subgroup of patients with spontaneous artery dissection.

Migraine headaches in adolescents: A five-year follow-up study

Background and Objectives.—Longitudinal studies of juvenile migraine are very few. We investigated the prevalence and evolution over 5 years of migraine without aura (MWOA) and migraineous disorder (MD) in an adolescent population.

Cognitive impairment in Behçet's disease patients without overt neurological involvement.

We investigated the prevalence of cognitive impairment in patients with Behçets disease (BD) without overt neurological involvement. The influence of disease duration, disease activity, prednisone dosage, and anxiety and depression levels was evaluated. Twenty-six consecutive BD outpatients and 26 healthy controls matched for age, education and sex completed a comprehensive neuropsychological battery including tests of memory, visuospatial and constructional abilities, language, attention and psychomotor speed, non-verbal reasoning and executive functioning. The Hamilton scales for anxiety and depression were administered. Disease activity was assessed using the Behçets Disease Current Activity Form (BDCAF). Compared to controls, BD patients were significantly impaired on tasks evaluating long-term verbal and non-verbal memory, and visuospatial skills. In addition, BD patients were significantly more anxious and depressed than controls. Cognitive impairment was evident in 46.1% of BD patients compared with none of control subjects (p<0.0001), with memory representing the cognitive domain most affected. Both high disease activity (OR 1.3, 95% CI 1.0-1.5, p<0.04) and high prednisone dosage (OR 1.3, 95% CI 1.0-1.7, p<0.03) were independently associated with cognitive impairment in BD after adjustment for demographic variables. Cognitive impairment, involving mainly memory functions, occurs frequently in BD patients. It may occur independently of clinically overt neurological involvement, and is more common in patients with an active disease and in those receiving prednisone.

Chronic paroxysmal hemicrania and hemicrania continua responding to topiramate: Two case reports.

Chronic paroxysmal hemicrania (CPH) is a rare primary headache syndrome, which is classified along with cluster headache and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing as a trigeminal autonomic cephalalgia (TACs). Hemicrania continua (HC) was previously classified as one of the TACs, but in the recent second classification of the International Headache Society this disorder was moved to the group of other primary headaches. Both CPH and HC are characterised by moderate to excruciating pain requiring pharmacological treatment; furthermore, both conditions are characterised by an absolute response to indomethacin, which represents one of the current diagnostic criteria for these two syndromes. Unfortunately, in about one-fourth of cases treatment with indomethacin may cause adverse events, mostly gastrointestinal. We report one subject with CPH and another with HC intolerant to indomethacin, who responded remarkably well to topiramate.

Prognosis of migraine headaches in adolescents A 10-year follow-up study

Objective: To determine the long-term outcome of migraine headaches in adolescents and to identify possible predictors of prognosis. Methods: Fifty-five of 80 subjects with migraine headaches (ages 11 to 14 years), who attended the baseline examination of a population-based study conducted in southern Italy in 1989, were eligible for follow-up in 1999. All interviews and examinations were conducted by neurologists, and migraine diagnoses were based on the International Headache Society (IHS) criteria. The association between possible prognostic factors and the long-term persistence of migraine headaches was explored using logistic regression analysis. Results: Of 55 subjects with migraine headaches at baseline, 41.8% had persistent migraine, 38.2% had experienced remission, and 20.0% transformed to tension-type headache. Only migraine without aura persisted in the same IHS code after 10 years, whereas migrainous disorder and nonclassifiable headache did not. The family history of migraine significantly predicted the 10-year persistence of migraine headaches (odds ratio [OR] = 7.0; 95% CI: 1.7 to 26.8). The risk persisted when only subjects with migraine with or without aura were evaluated (OR = 5.0; 95% CI: 1.2 to 20.9). Conclusions: Migraine headaches in adolescents have a favorable long-term prognosis. Familial disposition for migraine predicted a poorer outcome, especially in subjects with migraine without aura.

Interictal executive dysfunction in migraineurs without aura: relationship with duration and intensity of attacks

Subjects with migraine are at increased risk of subcortical white matter lesions (WML). Reports of cognitive testing in adults with migraine have yielded inconsistent results. We performed a cross-sectional study to assess whether migraine without aura (MwA) is associated with impairment in executive functioning, a typical cognitive correlate of subcortical WML. Forty-five subjects with MwA and 90 controls, matched for age and education, underwent a cognitive battery of tests evaluating executive functions. The following migraine characteristics were collected: age at onset and length of migraine history, and frequency, duration and intensity of attacks. Subjects with MwA performed significantly lower than controls in tests evaluating complex, multifactorial executive functions. After multiple adjustments, the duration and intensity of migraine attacks significantly predicted cognitive disturbances. In the interictal phase of MwA there is evidence of mild executive dysfunction. The cumulative effects of repeated migraine attacks on prefronto-cerebellar loop probably account for our results.

Association between apolipoprotein E ε4 allele and apathy in probable Alzheimer's disease

Objective:  There have been inconclusive results to date on the association between the Apolipoprotein E (ApoE) genotype and neuropsychiatric symptoms (NPS) in Alzheimers disease (AD). We investigated whether ApoE ɛ4 allele is associated with NPS in probable AD.

Lack of association between angiotensin converting enzyme polymorphism and sporadic Alzheimer's disease

Epidemiological and pathogenetic evidences suggest a strong association between vascular risk factors and sporadic Alzheimers disease (sAD). In agreement with the vascular hypothesis of AD, the role of various candidate genes for atherosclerosis has been investigated, leading to conflicting results. In order to clarify the significance of angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism in a group of patients with sAD, we conducted a case-control study including 149 cases and 149 age and sex matched controls. All subjects were genotyped for ACE and Apolipoprotein E (APOE). There were no significant differences in ACE genotype or allele frequencies between cases and controls, even after stratification for APOE4 carrier status. Our data suggest that the ACE I/D polymorphism is not associated to genetic susceptibility in sAD patients.