Fabricio Ferreira de Oliveira

Cognitive Impairment in Fibromyalgia

Cognitive and behavioral impairments are core manifestations of fibromyalgia and may be more disabling than pain itself. Involvement of the central nervous system is ascertained by the fact that frontoparietal and limbic cortices are often functionally and structurally affected along the course of this disease. Even though neuroimaging has brought some experimental evidence to support such network disruption, there are currently no clinically effective biomarkers that detect and quantify cognitive and behavioral disturbances in fibromyalgia; thus, traditional scales and tests of neuropsychiatric assessment remain the most important diagnostic tools. This review addresses the most common cognitive and behavioral impairments in people with fibromyalgia, while explaining their pathophysiological basis and currently available therapeutic options.

Pharmacological modulation of cognitive and behavioral symptoms in patients with dementia due to Alzheimer's disease

To evaluate correlations of pharmacological treatment with cognitive and behavioral symptoms in patients with dementia due to Alzheimers disease with low schooling, subjects were assessed for demographic features, neuropsychiatric symptoms, cognitive decline, functionality, caregiver burden, APOE haplotypes and pharmacological treatment. Among 217 patients, use of cholinesterase inhibitors with or without Memantine was associated with less neuropsychiatric symptoms, while anti-psychotics and/or anti-epileptic drugs were associated with lower instrumental functionality. Anti-psychotics were also associated with more neuropsychiatric symptoms in moderately impaired patients, possibly reflecting the greater need for such treatment when behavioral symptoms are present. Patients receiving more medications were usually younger, obese, married, with higher schooling and more neuropsychiatric symptoms. APOE4+ haplotypes were correlated with earlier dementia onset, but not with pharmacological treatment. Higher caregiver burden was associated with more psychotropic drugs. A trend was found for treatment with cholinesterase inhibitors and Memantine to be associated with longer lengths of dementia for moderately impaired but not for severely impaired patients, regardless of APOE haplotypes, translating into a synergistic effect among such medications for slowing cognitive decline but not for prolonging survival. Further longitudinal studies may be required to assess dose-response relationships regarding treatment with psychotropics for patients with dementia.

Risk factors for age at onset of dementia due to Alzheimer's disease in a sample of patients with low mean schooling from São Paulo, Brazil

In view of the mild effects of pharmacological treatment for dementia due to Alzheimers disease (AD), the search for modifiable risk factors is an important challenge. Although risk factors for AD are widely recognized, elements that influence the time of onset of the dementia syndrome have not been comprehensively reported. We aimed to investigate which risk factors might be associated with the age at onset of AD in a sample of patients with low mean schooling from São Paulo, Brazil.

Educational bias in the assessment of severe dementia: Brazilian cutoffs for severe Mini-Mental State Examination

UNLABELLED Cognitive assessment in advanced stages of Alzheimers disease (AD) is limited by the imprecision of most instruments. OBJECTIVE To determine objective cognitive responses in moderate and severe AD patients by way of the Severe Mini-Mental State Examination (SMMSE), and to correlate performances with Mini-Mental State Examination (MMSE) scores. METHOD Consecutive outpatients in moderate and severe stages of AD (Clinical Dementia Rating 2.0 or 3.0) were evaluated and compared according to MMSE and SMMSE scores. RESULTS Overall 400 patients were included, 67.5% females, mean age 76.6±6.7 years-old. There was no significant impact of age or gender over MMSE or SMMSE scores. Mean schooling was 4.4±2.5 years, impacting SMMSE scores (p=0.008). Scores on MMSE and SMMSE were significantly correlated (F-ratio=690.6325, p<0.0001). CONCLUSION The SMMSE is influenced by schooling, but not by age or gender, and is an accurate test for assessment of moderate and severe AD.

Brain-Penetrating Angiotensin-Converting Enzyme Inhibitors and Cognitive Change in Patients with Dementia due to Alzheimer's Disease

Controversy over benefits of angiotensin-converting enzyme inhibitors (ACEIs) for treatment of dementia due to Alzheimers disease (AD) led to this alternative investigational approach by the employment of pharmacogenetic methods, correlating the cognitive change of patients with late-onset AD with the presence of common ACE gene promoter polymorphisms, and stratifying the sample in groups of patients who responded or not to the brain-penetrating ACEIs Captopril or Perindopril. A trend was found for treatment with brain-penetrating ACEIs to slow cognitive decline in AD patients with the haplotype rs1800764 (CC): rs4291 (TT) (p = 0.024), and also non-significantly for independent carriers of rs1800764 or rs4291.

Correlations among cognitive and behavioural assessments in patients with dementia due to Alzheimer's disease.

AIMS Primarily, we sought to verify correlations among assessments for cognition, behaviour and functional independence in a sample of patients with dementia due to Alzheimers disease (AD). Secondarily, impacts of education, APOE haplotypes, length of dementia, age and alcohol use over the neuropsychiatric assessment were estimated. METHODS Patients with AD were assessed for demographic features, neuropsychiatric symptoms, cognitive test scores, functional impairment, caregiver burden and APOE haplotypes. Statistical comparisons were undertaken by way of Kruskal-Wallis test, linear regressions and Spearman correlations, significance at ρ < 0.05. RESULTS A total of 217 patients were included. Mean schooling was 4.21 ± 3.7 years, with significant impacts over cognitive tests. Mean age at examination was 78 ± 6.19 years-old, significantly influencing instrumental functionality. The mean length of the dementia syndrome was 5.4 ± 2.9 years, significantly impacting cognitive decline and functionality. Apathy was the most common behavioural symptom, negatively correlated with anxiety and delusions, and positively correlated with lifetime alcohol load. Patients with previous smoking or drinking habits were more likely to continue smoking or drinking later in life. APOE4+ haplotypes led to earlier dementia onset and significantly lower caregiver burden in mild dementia stages. CONCLUSIONS Most correlations among test results were highly significant, confirming that cognition, behaviour and functionality are usually interrelated in all stages of AD. Caregiver burden was correlated with behaviour, but not with cognition, and was lower for patients with APOE4+ haplotypes in mild dementia stages. Education is a major impact factor for cognitive performance.

Short-term prognosis for speech and language in first stroke patients

OBJECTIVE To evaluate the factors that can influence evolution of communication after a first stroke. METHOD Thirty-seven adult patients were evaluated for speech and language within 72 hours after a single first-ever ischemic brain injury and later on. Patients who were comatose, with decompensated systemic diseases, or history of chronic alcoholism or illicit drug use were not included. Brain CT and/or 2T-MR exams were solicited for topographic correlation. Size of infarct was classified as large or small according to the TOAST classification. RESULTS Patients who survived had lesser chances of presenting with aphasia or dysarthria 3 months after the stroke if the infarct size was small (p=0.017). Gender, age, schooling, aphasia subtype, infarct side and topography were non-significant in our sample. Subjects with global aphasia or lone cortical dysarthria had a slower evolution. CONCLUSION Brain injury size was the most influential factor for neurological outcome at 3 months post-stroke.

Assessment of risk factors for earlier onset of sporadic Alzheimer's disease dementia.

BACKGROUND Pharmacological treatment has mild effects for patients with Alzheimers disease dementia (AD); therefore, the search for modifiable risk factors is an important challenge. Though risk factors for AD are widely recognized, elements that influence the time of dementia onset have not been comprehensively reported. We aimed to investigate which risk factors might be related to the age of onset of AD in a sample of patients with highly variable educational levels, taking into account the Framingham risk scoring as the sole measure of vascular risk. SUBJECTS AND METHODS We included 209 consecutive late-onset AD patients to find out which factors among educational levels, coronary heart disease risk estimated by way of Framingham risk scores, history of head trauma or depression, surgical procedures under general anesthesia, family history of neurodegenerative diseases, gender, marital status and APOE haplotypes might be related to the age of dementia onset in this sample of patients with low mean schooling. RESULTS Mean age of AD onset was 73.38±6.5 years old, unaffected by schooling or family history of neurodegenerative diseases. Patients who were APOE-ε4 carriers, married, or with history of depression, had earlier onset of AD, particularly when they were women. Coronary heart disease risk was marginally significant for later onset of AD. CONCLUSIONS APOE haplotypes, marital status and history of depression were the most important factors to influence the age of AD onset in this sample. While midlife cerebrovascular risk factors may increase incidence of AD, they may lead to later dementia onset when present in late life.

Risk factors for cognitive and functional change in one year in patients with Alzheimer's disease dementia from São Paulo, Brazil.

Midlife cerebrovascular risk, low cognitive reserve and APOE4+ haplotypes are risk factors for Alzheimers disease dementia (AD). We prospectively searched for factors that might be associated with yearly changes in caregiver burden, cognition, basic and instrumental functionality in 193 consecutive outpatients with late-onset AD, namely gender, APOE haplotypes, schooling, age at AD onset, marital status, depression, cerebrovascular risk factors, serum TSH levels, cognitive and physical activities, and treatment with cholinesterase inhibitors or anti-psychotics, while also investigating associations between APOE haplotypes and patient participation in cognitive or physical activities. Higher education led to greater declines in instrumental functionality, whereas increases in body mass index were associated with rises in basic functionality and cognitive test scores. Established cerebrovascular risk factors had no independent effects over cognitive or functional change, but their combinations led to cognitive improvement, possibly related to enhanced cerebral perfusion in late life. Cholinesterase inhibitors improved caregiver burden. Enhanced instrumental functionality and steeper cognitive decline by the use of anti-psychotics might be attributed to improved behavioural symptoms and neuropsychiatric side effects, respectively. Each copy of APOE-ε4 (β=-0.102) led to cumulative decreased participation in physical activities (ρ=0.015). These results might impact public health policies and the interpretation of clinical trials for AD.

Global aphasia as a predictor of mortality in the acute phase of a first stroke

OBJECTIVE To establish whether vascular aphasic syndromes can predict stroke outcomes. METHOD Thirty-seven adults were evaluated for speech and language within 72 hours after a single first-ever ischemic brain lesion, in blind association to CT and/or MR. RESULTS Speech or language disabilities were found in seven (87.5%) of the eight deceased patients and twenty-six (89.7%) of the twenty-nine survivors. Global aphasia was identified in eleven patients, all with left hemisphere lesions (nine mute; five deceased), consisting on a risk factor for death in the acute stroke phase (ρ=0.022). Age (z=1.65; ρ>0.09), thrombolysis (ρ=0.591), infarct size (ρ=0.076) and side (ρ=0.649) did not significantly influence survival. Absence of aphasia did not predict a better evolution, regardless of the affected hemisphere. Prevalence of cardiovascular risk factors was similar for all patient groups. CONCLUSION Global aphasia in acute stroke can adversely affect prognosis, translated into impairment of dominant perisylvian vascular territories, with mutism as an important semiological element.