Neurological and psychiatric predictors of mortality in patients with Alzheimer disease in California

OBJECTIVE: To determine whether neurological and psychiatric symptoms predict survival time among patients with Alzheimer disease (AD) after adjusting for the influence of sociodemographic variables, health conditions, and dementia severity separately for men and women. DESIGN: The sample consisted of 936 men and women diagnosed as having probable or possible AD at 1 of 7 Alzheimer's Disease Diagnostic and Treatment Centers throughout California from 1986 through 1990. Data on dementia severity, comorbid conditions, and demographic characteristics were collected at the time of AD diagnosis. Data on vital status and dates of death were obtained by linking the patient file to several administrative databases maintained by the California State and federal governments. The mean length of follow-up was 31 months. Data were analyzed with Kaplan-Meier survival curves and Cox proportional hazards models. RESULTS: Men had shorter survival times than did women (log-rank test, 30.93, P < .001). Among men, but not women, survival times were negatively associated with selected neurological and psychiatric symptoms. Among women, but not men, a history of cardiovascular conditions was associated with poorer survival. CONCLUSIONS: Patterns of survival and predictors of survival time among patients with AD differ by sex. Future studies of survival and progression of AD need to examine men and women separately.     

Comparison of young and adult driver crashes in Alaska using linked traffic crash and hospital data

This report describes young driver crashes in Alaska, compares rates and characteristics of young driver crashes with adult driver crashes, and summarizes the medical and financial outcomes of young driver crashes, for the period 1991 through 1995. Using the Mini Crash Outcome Data Evaluation System (MINICODES), trauma registry hospital discharge data were linked with traffic crash records. The data were analyzed to compare drivers aged 16-20 with drivers aged 21-50 who were involved in a crash resulting in the hospitalization or death of a crash victim. The CrashCost Program was used to estimate costs associated with young driver crashes for the five years. Young drivers were 2.9 times more likely than adult drivers to be involved in crashes that resulted in the hospitalization of a crash victim, and 2.6 times more likely to be involved in a crash involving a fatality. The contributing factors for young driver crashes were listed as human factors 73.4% of the time, compared with 65.6% among adults (P = .001). Costs associated with the young driver crashes were estimated to be over $300 million, which resulted in a cost per young licensed driver that was 3.4 times the cost per adult licensed driver.     

Alcohol use, driver, and crash characteristics among injured motorcycle drivers

BACKGROUND: Motorcycle drivers have the highest frequency of alcohol use among all road users. This study examines alcohol use among a large sample of injured motorcycle drivers and examines how crash characteristics differ with the use of alcohol. METHODS: Over 3000 motorcycle drivers who crashed between January 1, 1991, and December 31, 1992, were studied. All fatally injured drivers in 11 California counties and a sample of nonfatally injured drivers treated in 28 hospitals were included in the study if a crash report and medical record were available. RESULTS: Among drivers tested for alcohol use, 42% tested positive for the presence of alcohol. Drinking drivers were more likely to be speeding and less likely to wear a helmet, and more frequently had single motorcycle crashes than nondrinking drivers. Crash characteristics, but not alcohol use, were predictive of increased injury severity. CONCLUSIONS: Alcohol use remains a significant factor in motorcycle crashes and is an important area for injury prevention efforts.     

Identifying crash involvement among older drivers: agreement between self-report and state records

Methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity is thought to be associated with the formation of free radicals. Since evidence suggests that melatonin may act as a free radical scavenger and antioxidant, the present study was undertaken to investigate the effect of melatonin on METH- and MPTP-induced neurotoxicity. In addition, the effect of melatonin on METH-induced locomotor sensitization was investigated. The administration of METH (5 mg kg(-1) x 3) or MPTP (20 mg kg(-1) x 3) to Swiss Webster mice resulted in 45-57% depletion in the content of striatal dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 57-59% depletion in dopamine transporter binding sites. The administration of melatonin (10 mg kg(-1)) before each of the three injections of the neurotoxic agents (on day 1), and thereafter for two additional days, afforded a full protection against METH-induced depletion of dopamine and its metabolites and dopamine transporter binding sites. In addition, melatonin significantly diminished METH-induced hyperthermia. However, the treatment with melatonin had no significant effect on MPTP-induced depletion of the dopaminergic markers tested. In the set of behavioral experiments, we found that the administration of 1 mg kg(-1) METH to Swiss Webster mice for 5 days resulted in marked locomotor sensitization to a subsequent challenge injection of METH, as well as context-dependent sensitization (conditioning). The pretreatment with melatonin (10 mg kg(-1)) prevented neither the sensitized response to METH nor the development of conditioned locomotion. Results of the present study indicate that melatonin has a differential effect on the dopaminergic neurotoxicity produced by METH and MPTP. Since it is postulated that METH-induced hyperthermia is related to its neurotoxic effect, while regulation of body temperature is unrelated to MPTP-induced neurotoxicity or METH-induced locomotor sensitization, the protective effect of melatonin observed in the present study may be due primarily to diminishing METH-induced hyperthermia.     

APOE-epsilon 4 in patients with Alzheimer disease and vascular dementia

This study reports seven cases of epulis excised by the CO2 laser without anesthesia. The laser was used in a continuous wave mode at power setting of 2-4 W. All lesions were excised completely, and no patients felt pain during laser irradiation. The operation was successful without using surgical packs, and there was no postoperative discomfort. There has been no evidence of recurrence after operation.     

Advantages in long-term treatment with Cognex in Alzheimer disease

Early diagnosis and treatment of AD is critical to maximize benefits for the patient and the caregiver. It is important to intervene early in the illness, before the quality of life of the patient and the caregiver has deteriorated to the point where treatment only prolongs an already difficult situation. If treatment begins early enough in the disease course, loss of functional independence may be delayed, just as nursing home placement was delayed in this study. In this way, quality of life is improved for both the patient and the caregiver.     

Cognitive loss in dementia with Lewy bodies and Alzheimer disease

BACKGROUND: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. Some preliminary evidence exists that the pattern of cognitive impairment in DLB is different from that in Alzheimer disease (AD). OBJECTIVE: To delineate features of cognitive impairment of DLB on standardized neuropsychological tests. METHODS: We performed neuropsychological assessments of 26 patients with probable DLB (based on criteria of the consortium on DLB international workshop) and of 52 patients with probable AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke [now the National Institute of Neurological Disorders and Stroke])-Alzheimer's Disease and Related Disorders Association) who were matched to the patients with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. RESULTS: Compared with the group with probable AD, the group with probable DLB scored significantly lower on the picture arrangement, block design, object assembly, and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised and on the Raven Colored Progressive Matrices test and significantly higher on the Mini-Mental State Examination locational orientation subtest and the Alzheimer's Disease Assessment Scale word recall subtest. A discriminant analysis revealed that the word recall score on the Alzheimer's Disease Assessment Scale and the block design score on the Wechsler Adult Intelligence Scale-Revised were the best discriminant factors. CONCLUSIONS: The disproportionately severe visuoperceptual, visuoconstructive, and visuospatial dysfunction and the disproportionately mild memory impairment in DLB compared with AD, which likely reflect the distribution of the pathologic changes in DLB, can help to differentiate DLB from AD.     

Amyloid beta protein and Alzheimer disease

Amyloid beta protein is predominant in senile plaques, the neuropathologic hallmarks of Alzheimer disease. Researchers in Winnipeg have shown that this protein can overstimulate certain hydrolytic enzymes to break down the phospholipid building blocks of the brain-cell wall. They speculate that the abnormal destruction of phospholipids gradually drains the energy resources a neuron uses to rebuild its membrane. As neurons "burn out," the brain loses its ability to function normally. In view of evidence that NSAID therapy may interfere with the hydrolysis of phospholipids, the researchers will focus on finding an NSAID-related compound effective against Alzheimer disease.     

Use of cholinesterase inhibitors in Alzheimer disease

According to the cholinergic theory of Alzheimer's disease, the cognitive failure depends on a deficit in acetylcholine. The study reported above examines the efficacy and tolerability of cholinesterase inhibitors, such as tetrahydroamino acridine (THA), for the management of this pathology.     

Abnormalities of mitochondrial enzymes in Alzheimer disease

Abundant evidence, including critical information gathered by Prof. Siegfried Hoyer and his colleagues, indicates that abnormalities of cerebral metabolism are common in neurodegenerative diseases, including Alzheimer's Disease (AD). Alterations in mitochondrial enzymes likely underlie these deficits. Replicable reductions in AD brain occur in the pyruvate dehydrogenase complex (the link of glycolysis to the Kreb's cycle), the alpha-ketoglutarate dehydrogenase complex (KGDHC; the link of Kreb's cycle to glutamate metabolism) and cytochrome oxidase (the link of the Kreb's cycle to oxygen utilization). Available evidence suggests that deficiencies in KGDHC may be genetic in some cases, whereas evidence that the other two enzyme systems have a genetic component is lacking. Additional results indicate that the reductions can also be secondary to other causes including oxidative stress. A variety of data suggest that the mitochondrial insufficiencies contribute significantly to the pathophysiology of AD.     

Simulated airborne spread of Aujeszky's disease and foot-and-mouth disease

The atmospheric dispersion of virus was simulated using a computer model which had been developed for predicting the dispersion of toxic gases from chemical engineering plants. The results were compared with data from four outbreaks in which virus was believed to have been transported by air: two outbreaks of foot-and-mouth disease in the United Kingdom in 1967 and outbreaks of Aujeszky's disease in Yorkshire in 1981 to 1982 and Indiana in 1988. There was relatively good agreement with most of these data. The paper shows that the model could be useful in an emergency because the risk of virus spread could be predicted in real time.     

Genetics, ethics, and Alzheimer disease

This article considers the emerging research on Alzheimer disease (AD) genetics in relation to ethical questions surrounding presymptomatic and prenatal genetic testing. Given the rapid advance in AD genetics over the past 8 years, it is likely that the attention of clinicians and ethicists will increasingly turn to genetic issues. After a survey of current genetic knowledge, this article addresses 3 areas of likely ethical concern. While AD genetic screening programs are currently rare and restricted to specific pedigrees, they will become more common in the future. It is, therefore, imperative that society and clinicians begin to consider the ethical issues this raises.     

Quantitative spectral electroencephalography in predicting survival in patients with early Alzheimer disease

OBJECTIVE: To determine whether measures of quantitative spectral electroencephalography (EEG) can predict survival in patients with early Alzheimer disease. DESIGN: Prospective cohort study; median duration of follow-up was 4.4 years in survivors and 2.6 years in nonsurvivors. Cox proportional hazards models, with adjustment for age and sex were used to estimate relationships between EEG measures and survival. Log relative percentage values of EEG bands were used as predictors. SETTING: Outpatient university memory clinic. PARTICIPANTS: One hundred one consecutively referred patients with early probable Alzheimer disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria were studied with EEG at the time of diagnosis. The mean age of the patients was 79.2 years, which was higher than in previous EEG studies. MAIN OUTCOME MEASURE: Mortality. RESULTS: Fifty-one patients (50.5%) died during follow-up, with a median survival time in all patients of 4.1 years. The following EEG variables were significantly associated with increased risk of mortality: from parieto-occipital leads, higher theta (hazard ratio, 2.05; 95% confidence interval, 1.15-3.66; P<.05), lower alpha (hazard ratio, 0.43; 95% confidence interval, 0.25-0.76; P<.01), and lower beta (hazard ratio, 0.38; 95% confidence interval, 0.22-0.68; P<.001) activity; and from frontocentral leads, higher theta activity (hazard ratio, 2.07; 95% confidence interval, 1.17-3.66; P<.05). Stepwise Cox regression analysis showed that loss of parieto-occipital beta (P<.01) and alpha (P<.05) power were independent and significant predictors of mortality. Both beta (12.6-35.4 Hz) and alpha (7.5-12.5 Hz) activity remained significantly associated with mortality after adjustment for education, dementia severity, symptom duration, level of cognitive function, presence of extrapyramidal symptoms or hallucinations, presence of vascular risk factors, and presence of leukoaraiosis or local cortical atrophy. CONCLUSIONS: Decreases of beta and alpha activity on quantitative spectral EEG are independent predictors of mortality in patients with early Alzheimer disease. In the clinical context, the use of EEG technology for prediction of survival in individual patients remains to be determined.     

Studies of the enteric nervous system in Alzheimer disease and other dementias of the elderly: enteric neurons in Alzheimer disease

Nitric oxide is a biological mediator. In nervous system it acts like neurotransmitter and also modulate acute inflammation. In the peripheral nervous system it blocks the nociceptive stimulus through an increase in postsynaptic neurone GMPc level. Nitro-vasodilator drugs like nitroglycerin are metabolised in the cell given rise to short lived intermediates, which liberating nitric oxide that activate the guanylate cyclase enzyme, increasing the GMPc in smooth muscle cell. This study show that nitroglycerin produces an analgesic action. The pain sensitivity to pinprick test in forearm with nitroglycerin has shown a decrease in a significative manner against placebo. We speculate that nitroglycerin could have a similar action as endogenous nitric oxide in nervous system.     

Treatment of Alzheimer disease with tacrine: a cost-analysis model

In a cost-analysis model, the effect on the costs of Alzheimer disease of tacrine (tetrahydroaminoacridine) treatment was studied. A model of the survival of the Swedish Alzheimer disease population was constructed in which the placement of patients with Alzheimer disease in care organization was assumed to be influenced by the use of tacrine. Based on this model, the cost analysis was performed. Fifty-two percent of the Alzheimer disease population with an initial Mini-Mental State Examination (MMSE) score of 10 to 24 points are in the main alternative of the model treated with 160 mg tacrine with an initial improvement in MMSE of 2.6 points. The benefit of tacrine was a cost reduction of 1.3% when the results were calculated for the entire Alzheimer disease population. This corresponds to a benefit of 1.3 billion Swedish kronor (SEK) (with 3% discount rate) for the entire estimated survival period. The annual benefit per patient was estimated as 2,900 SEK [approximately U.S. $320 (1993)]. In the sensitivity analysis, the range was between -0.6% and 5.2%. Beginning treatment in the early stages of Alzheimer disease results in lower costs than a later start. The main conclusion is that tacrine, according to the model, has beneficial but modest effects on the costs of Alzheimer disease in Sweden.     

Safety in work vehicles: A multilevel study linking safety values and individual predictors to work-related driving crashes.

Although work-related driving is associated with high accident rates, limited research has investigated the factors influencing driving crashes in the work setting. This study explored multilevel influences on self-reported crashes in the workplace by surveying a sample of work-related drivers (n = 380), their workgroup supervisors (n = 88), and fleet managers (n = 47). At the driver level of analysis, safety motivation predicted self-reported crashes. In turn, drivers' perceptions of their fleet managers' safety values (but not drivers' perceptions of their supervisors' safety values), their own attitudes, and their own efficacy beliefs predicted motivation to drive safely. Furthermore, the influence of supervisors and fleet managers interacted such that drivers were more motivated to drive safely if they perceived both their supervisor and fleet manager to value safety. This study also explored the cross-level relationships between supervisors' and fleet managers' perceptions of organizational safety values and drivers' perceptions of managerial safety values and found a relationship between fleet managers' perceptions of organizational safety values and drivers' perceptions of fleet managers' safety values. These results illustrate that perceptions of workplace safety values are transmitted across levels of the organization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)