Differential Expression of Ribosomal Genes in Brain and Blood of Alzheimer's Disease Patients.

Changes in rRNA and rDNA expression have been associated with cellular and organism aging and have been linked to Alzheimer's disease (AD) pathogenesis. In this study, we investigated the mRNA expression of ribosomal genes (28S/18S) and ß-amyloid precursor protein (APP) in different post mortem brain tissue regions (the entorhinal and auditory cortices and the hippocampus) of AD patients and elderly control subjects and also evaluated the extent of expression in peripheral blood from young, healthy, elderly, and Alzheimer's disease patients in order to investigate whether these individuals experienced the effects of aging. The comparative threshold cycle (CT) method via Real Time Polymerase Chain Reaction and the Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) were used to analyze gene expression and the Apolipoprotein E (APOE) genotype, respectively. When the brain areas were analyzed collectively, we observed a significant decrease in APP expression and a significant increase in levels of mRNA of 18S and 28S in Alzheimer's disease patients compared to healthy elderly individuals. Furthermore, there was a significant upregulation of 28SrRNA in the entorhinal cortex and hippocampus, but not in the auditory cortex of patients with AD. On the other hand, tests of blood samples verified a decreased expression of 28S rRNA in patients with AD. These results support the hypothesis that changes in rRNA are present in AD patients, are tissue-specific, and seem to occur independently and differently in each tissue. However, the next challenge is to discover the mechanisms responsible for the differences in expression observed in the blood and the brain in both healthy elderly individuals and Alzheimer's disease patients, as well as the impact of these genes on AD pathogenesis.

Social anxiety score is high in adolescents with chronic migraine.

BACKGROUND: Social anxiety disorder, also known as social phobia, is a marked and persistent fear of one or more social or performance situations in which the person is exposed to unfamiliar people or to possible scrutiny by others. It usually begins in mid-adolescence and has a chronic course and interferes in academic, social, family and personal functioning. Recent studies have shown that social anxiety disorder is more prevalent in adults with migraine. Little evidence on this subject is available for the adolescent population. METHODS: This study was performed between August 2009 and August 2010; all patients were recruited in schools, pediatric or neuropediatric facilities, and were submitted to a detailed headache questionnaire, which consisted of demographic and clinical data. To evaluate social anxiety, the Social Phobia Inventory was used. RESULTS: A total of 151 subjects were evaluated: 50 had chronic migraine, 50 had episodic migraine and 51 were control subjects. In the chronic migraine group, the mean score in the Social Phobia Inventory was 18.5 ± 12.4, which was significantly higher than in the episodic migraine group (12.1 ± 8.1) and in the control group (13.8 ± 10.8; F(2131) = 4.8, P= 0.010). The mean score, however, was not significantly different between the control and episodic migraine groups. CONCLUSIONS: Chronic migraine is strongly associated with high social anxiety score, regardless of demographic data and pain intensity. The total burden of migraine may be increased with social anxiety disorder comorbidity.

Urinary 6-sulphatoxymelatonin levels are depressed in chronic migraine and several comorbidities.

OBJECTIVE: To assess urinary 6-sulphatoxymelatonin levels in a large consecutive series of patients with migraine and several comorbidities (chronic fatigue, fibromyalgia, insomnia, anxiety, and depression) as compared with controls. BACKGROUND: Urine analysis is widely used as a measure of melatonin secretion, as it is correlated with the nocturnal profile of plasma melatonin secretion. Melatonin has critical functions in human physiology and substantial evidence points to its importance in the regulation of circadian rhythms, sleep, and headache disorders. METHODS: Urine samples were collected into a single plastic container over a 12-hour period from 8:00 pm to 8:00 am of the next day, and 6-sulphatoxymelatonin was measured by quantitative ELISA. All of the patients were given a detailed questionnaire about headaches and additionally answered the following questionnaires: Chalder fatigue questionnaire, Epworth somnolence questionnaire, State-Trait Anxiety Inventory, and the Beck Depression Inventory. RESULTS: A total of 220 subjects were evaluated - 73 (33%) had episodic migraine, 73 (33%) had chronic migraine, and 74 (34%) were enrolled as control subjects. There was a strong correlation between the concentration of 6-sulphatoxymelatonin detected and chronic migraine. Regarding the comorbidities, this study objectively demonstrates an inverse relationship between 6-sulphatoxymelatonin levels and depression, anxiety, and fatigue. CONCLUSIONS: To our knowledge, this is the first study to evaluate the relationship between the urinary concentration of melatonin and migraine comorbidities. These results support hypothalamic involvement in migraine pathophysiology.

Subjective memory complaints, white-matter lesions, depressive symptoms, and cognition in elderly patients.

OBJECTIVES: Subjective memory complaints (SMC) and cerebral white-matter lesions (WML) are very prevalent among elderly subjects, but their clinical significance is controversial. The authors sought to determine whether SMCs are related to WML, independently of the presence of depressive symptoms, which are known to be associated with both. The relationship between SMC and cognition was also examined. METHODS: This is a cross-sectional study on 60 elderly subjects without dementia. All subjects underwent FLAIR and T2-weighted axial MRI scans, a memory-complaint questionnaire, a geriatric depression scale, and a comprehensive cognitive assessment. RESULTS: Multiple linear regression showed that although the best correlate of SMC was the severity of depressive symptoms, SMC and WML were strongly correlated. Objective cognitive performance was not significantly associated with SMC after adjusting for WML and mood. The presence of a history of late-onset depression was a strong correlate of WML severity, even after adjusting for age, gender, and education. CONCLUSIONS: Complaints of cognitive decline are significantly associated with the severity of WML, independently of level of cognition and depression.

What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson's disease with dementia.

BACKGROUND: This open label study was designed to assess the effects of donepezil treatment, its withdrawal and subsequent recommencement on cognitive functioning, behaviour and parkinsonian symptoms in patients with probable dementia with Lewy bodies (DLB) and with Parkinson's disease who subsequently developed dementia (PDD). METHODS: Eight patients with DLB and 11 with PDD were treated with up to 10 mg of donepezil daily for 20 weeks followed by a 6-week withdrawal period. The primary outcome measures were the Mini-Mental State Examination (MMSE), the total Neuropsychiatric Inventory (NPI) and the Unified Parkinson's Disease Rating Scale III. Testing was conducted before dosing, at week 20, at a withdrawal visit and 3 months after recommencement on donepezil. RESULTS: Patients with DLB and PDD showed a significant improvement in cognition with treatment, loss of this improvement on withdrawal and restoration of treatment gains on recommencement. Both groups also demonstrated favourable, behavioural changes with treatment, PDD patients in particular deteriorating significantly after withdrawal. The only NPI symptom domain that showed a consistent significant response to both treatment (positive) and withdrawal (negative) was hallucinations. The medication was well tolerated and parkinsonian features did not alter significantly over the testing sessions. CONCLUSIONS: Our results suggest that treatment with donepezil improves cognition and hallucinations without increasing parkinsonian symptoms, and its sudden withdrawal is usually detrimental, producing acute cognitive and behavioural decline. Although recommencement on donepezil appears to reverse this deterioration we do not advise its abrupt discontinuation in this population.

Serviço Integrado de Neurogeriatria. Ambulatório da Memória - Análise dos resultados iniciais / Neurogeriatric Integrated Service. Memory Clinic - description of the initial results

Demência é o declínio da capacidade intelectual e adequação social em grau suficiente para afetar as atividades de vida diária. A demência pode ter várias etiologias, sendo algumas reversíveis. O Ambulatório da Memória do Serviço Integrado de Neurogeriatria da Real e Benemérita Sociedade Portuguesa de Beneficência - Hospital São Joaquim - propõe um modelo de atendimento multidisciplinar para o diagnóstico e tratamento das síndromes demenciais, com os seguintes resultados preliminares: dos 104 pacientes, 10 (9,6 por cento) não apresentavam deterioração intelectual. Dos 94 demais, 27 (28,7 por cento) tinham afecções potencialmentereversíveis: 18 casos de doença psiquiátrica; dois de doenças metabólicas; três de intoxicações exógenas e 4 casos de hidrocefalia. Foram 67 casos (71,2 por cento) de perda cognitiva causada por lesão estrutural, dos quais 42 pacientes (62,5 por cento) tinham doença de Alzheimer, que, atualmente possui tratamento específico. A proposta de uma equipe multidisciplinar, bem estruturada, pode beneficiar estes pacientes e seus familiares