Neurological Disorders in an Elderly Cohort Experienced Past Stressful Events: A Retrospective-prospective Study.

BACKGROUND: Psychological stress may be a risk factor for dementia, but the association between exposure to stressful life events and the development of cognitive dysfunction has not been conclusively demonstrated. We hypothesize that if a stressful event has an impact on the subjects, its effects would be different in the three diseases. OBJECTIVE: This study aims to assess the effects of stressful events in senior patients who later developed ischemic stroke, Alzheimer's, or Parkinson's disease. MATERIAL AND METHODS: Together with demographic variables (age, sex, race, socioeconomic and cultural levels), five types of past stressful events, such as death or serious illness of close relatives, job dismissal, change of financial status, retirement, and change of residence, were recorded in 1024 patients with Alzheimer's disease, Parkinson's disease, and ischemic stroke. Time-todiagnosis (months from the event to the first symptoms: retrospective study) and evolution time (years of follow-up of each patient: prospective study) were recorded. The variance and nonparametric methods were analyzed to the variables time-to-diagnosis and evolution time to analyze differences between these diseases. RESULTS: The demographic variables, such as age, sex, race, economic and cultural levels, were found to be statistically non-significant; differences in the economic level were significant (P<0.05). Significant differences (P<0.001) were found in the mean time-to-diagnosis between diseases (Alzheimer's disease>Parkinson's disease >Stroke), and minor differences (P<0.05) in evolution time. CONCLUSION: Differences in time-to-diagnosis between the diseases indicate that the stressful effect of having experienced the death or serious illness of a close relative has an impact on their emergence. The measurement of time-to-diagnosis and evolution time proves useful in detecting differences between diseases.

Daily Living Activities and Cognition in Aged Patients: Effect of Acute Systemic Diseases and Stroke on Leukoaraiosis.

BACKGROUND: Acute Systemic Diseases (ASD) impact on extended leukoaraiosis (ExLA) have been seldom described. We study the deterioration in daily life activities (DLA) and cognition associated with ASD events compared with the well-described impacts of stroke in patients with leukoaraiosis (L-A). METHODS: Cross-sectional surveys of aged adults from the emergency room after an acute event of ASD or stroke, hospitalized or receiving home care, were followed for one year. From 268 initial patients 206 were included in the study, all with moderate to severe L-A (Fazekas 2 and 3). The Clinical Deterioration Rating (CDR) and the modified Rankin scale with structured interview were obtained one week previous to admission and after 3 and 12 months of evolution. Comparisons were conducted within and between groups with nonparametric techniques. RESULTS: We formed three groups of similar age, A: Inpatients with one Stroke, B: Inpatients with one ASD, and C: Outpatients with one ASD. A sudden deterioration in Rankin was evident in Group A, while in B and C impairment was progressive. Impairment in CDR was smooth in all groups while in Rankin it was always greater than in cognition (CDR). No differences were found in the associations between groups and risk factors, hypertension being the most frequent one. CONCLUSION: ASD in ExL-A causes a worsening of DLA and cognition similar to that observed in ExL-A with concomitant stroke indicating the need, in ageing patients, of differential diagnosis in order to achieve the best possible treatment.

Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients.

AIM: To evaluate the cognitive performance of a homogeneous population of Alzheimer's disease (AD), non-demented Type 2 Diabetes Mellitus (DIAB), demented with concomitant diseases (AD+DIAB) and healthy control subjects. AD is a progressive dementia disorder characterized clinically by impairment of memory, cognition and behavior. Recently, a major research interest in AD has been placed on early evaluation. Diabetes is one of the clinical conditions that represent the greatest risk of developing oxidative stress and dementia. Glucose overload, leading to the development of impaired-induced insulin secretion in DIAB and has been suggested to slow or deter AD pathogenesis. METHODS: The degree of cognitive impairment was determined on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) and the Folstein's Mini Mental State Examination (MMSE); the severity of dementia was quantified applying the Clinical Dementia Rating (CDR) test; the Hamilton test was employed to evaluate depressive conditions; the final population studied was 101 subjects. RESULTS: The cognitive deterioration is statistically significantly lower (p<0.05) in AD+DIAB patients as compared with AD patients. CONCLUSIONS: In this longitudinal study the superimposed diabetic condition was associated with a lower rate of cognitive decline, while diabetic non-demented patients and controls present normal scores.

Systemic oxidative stress associated with the neurological diseases of aging.

Markers of oxidative stress were measured in blood samples of 338 subjects (965 observations): Alzheimer's, vascular dementia, diabetes (type II) superimposed to dementias, Parkinson's disease and controls. Patients showed increased thiobarbituric acid reactive substances (+21%; P < 0.05), copper-zinc superoxide dismutase (+64%; P < 0.001) and decreased antioxidant capacity (-28%; P < 0.001); pairs of variables resulted linearly related across groups (P < 0.001). Catalase and glutathione peroxidase, involved in discrimination between diseases, resulted non-significant. When diabetes is superimposed with dementias, changes resulted less marked but significant. Also, superoxide dismutase resulted not linearly correlated with any other variable or age-related (pure Alzheimer's peaks at 70 years, P < 0.001). Systemic oxidative stress was significantly associated (P << 0.001) with all diseases indicating a disbalance in peripheral/adaptive responses to oxidative disorders through different free radical metabolic pathways. While other changes - methionine cycle, insulin correlation - are also associated with dementias, the responses presented here show a simple linear relation between prooxidants and antioxidant defenses.

Homocysteine, vitamin B 12 and folate in Alzheimer's and vascular dementias: the paradoxical effect of the superimposed type II diabetes mellitus condition.

BACKGROUND: Increased concentration of plasmatic homocysteine (tHcy) and decreased vitamin B 12 (B12) and folate (FOL) are associated with Alzheimer's (AD) and vascular (VaD) dementias, with type II diabetes mellitus (DM), and reported as risk factors of these diseases. METHODS: The sample (n=122; males=60; mean age=73+/-7 years) comprised AD and VaD patients without DM, with a concomitant DM (AD+DM, VaD+DM), DM alone and controls (CTR), resulting in 6 groups. tHcy, B12 and FOL were determined in duplicate. RESULTS: The one-way ANOVA yielded significant differences between groups for all variables: tHcy p<10(-12); B12 p<10(-3); FOL p<10(-4). Significance for comparisons between groups was set at alpha=0.05, using the Bonferroni's statistic. The comparisons: DM vs. CTR, AD+DM vs. AD, VaD+DM vs. VaD, and DM demented vs. DM non-demented resulted significant for all variables, except for B12 in 2 comparisons. CONCLUSIONS: In demented and control subjects, tHcy and FOL exhibit extreme differences, not so marked between DM and controls. Demented patients with concomitant diabetes are closer to controls than their non-diabetic counterparts. Diabetes affects tHcy and FOL values, which are changed with opposite sign to non-demented. These results suggests a paradoxical phenomenon when diabetes is superimposed to dementias.

Oxidative stress in Alzheimer's and vascular dementias: masking of the antioxidant profiles by a concomitant Type II diabetes mellitus condition.

Oxidative stress is associated with Alzheimer's (DAT) and vascular (VD) dementias, as well as Type II diabetes mellitus (DIAB) and affected by hypoglycemic therapy. The population (n = 122; males = 60; mean age = 72.57 +/- 7.06) consisted of controls (CTR), DAT and VD patients, with (DAT + DIAB, VD + DIAB) and without concomitant DIAB, resulting in six groups where the antioxidant profile was determined: copper-zinc superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), and total antioxidant capacity (TRAP). The results were analyzed using a two-way ANOVA design and Bonferroni statistic. The ANOVAs yielded significant differences between groups for all components of the profile: SOD, p = 0.00000006; TBARS, p = 0.0000012; TRAP, p = 0.0000003. The significance level for comparisons between groups was set at alpha = 0.05. The comparisons DIAB vs. CTR, DAT+DIAB vs. DAT, and DIAB demented vs. DIAB non-demented resulted significant for all variables. VD + DIAB vs. VD resulted significant for all variables except TRAP. The antioxidant profiles of DIAB and CTR are different. The differences cannot be directly related with what is observed in dementias. The differences in profiles of demented and non-demented are somewhat hidden when demented patients are affected by a concomitant DIAB condition and/or hypoglycemic treatment, thus conditioning the diagnostic value for dementias of the profiles.

Stroke vs. chronic progressive cerebrovascular disease: a magnetic resonance imaging study of symptomatic outpatients.

Stroke is the main manifestation of cerebrovascular disease (CVD). Few studies report the insidious and progressive development of CVD. The aim of this study was the characterization of a CVD form without stroke in association with vascular subtypes and risk factors (VRF). From 105 CVD patients, 65 had stroke (62%), 13 of them had more than one stroke (20%), and 40 patients had a chronic progressive form (CPF) (38%). Mean evolution times up to maximum neurological deficiency were 1.57+/-0.94 and 344.25+/-210.96 days, respectively. Group results significantly associated with VRFs: hypertension (p=0.0046), hyperlipemia (p=0.0046) and atrial fibrillation (p=0.0173); with clinical manifestations: aphasia (p=0.0018), pyramidal syndrome (p=0.0000001) and small vessel disease (SVD) (p=0.0000001); and with MRI: bilateral infarctions (p=0.00009) and incomplete white matter lesions (IWMLs) (p=0.0061). Within the CPF group, dysarthria and complete infarctions were associated (p=0.00036). Most neurological disorders associated with CVD are related to CPF. The significant correlations of SVD, bilateral infarcts, IWMLs, dysarthria, several VRFs and the strong difference in evolution time up to maximum neurological deficiency values characterize CPF as a separate entity within CVD.