Mortality Risk after Diagnosis of Early-Onset Alzheimer's Disease versus Late-Onset Alzheimer's Disease: A Propensity Score Matching Analysis.

BACKGROUND/OBJECTIVE: We aimed to compare the risk of mortality in patients with early-onset Alzheimer's disease (EOAD) versus those with late-onset AD (LOAD) using a large number of study subjects. We applied propensity score matching (PSM) to minimize confounding biases in the comparison between EOAD and LOAD. METHODS: We obtained data from elderly Korean subjects with AD (n = 3,611) at baseline from the CREDOS cohort study, which was conducted from November 2005 to July 2013. We conducted PSM to reduce the bias due to confounding variables related to survival in patients with AD. The risks of mortality associated with EOAD and LOAD were evaluated by Cox proportional hazard analyses, controlling for relevant covariates. RESULTS: After propensity score matching, 312 subjects with EOAD and 624 subjects with LOAD were selected for further analysis. The Cox proportional hazard analysis showed that patients with EOAD are at a greater risk for mortality compared to those with LOAD (Hazard Ratio: 2.01, 95% CI: 1.01-4.00, p-value: 0.04) when controlling for the direct effect of aging on mortality. The results did not change after adjusting for age at diagnosis, general cognitive function, nutritional factor related to body mass index, and physical disability using activities of daily living. The results support the assumption that EOAD takes a more malignant course than LOAD. CONCLUSIONS: Our results provide support for the idea that EOAD takes a clinical course that is distinct from that of LOAD, especially as pertains to the risk of mortality.

Perceived sleep quality is associated with depression in a Korean elderly population.

Our study aimed to examine the relationship between perceived sleep quality and depression using Pittsburgh Sleep Quality Index (PSQI) and Cole's model to materialize the concept of perceived sleep quality in the non-cognitively impaired elderly. Older adults aged 60+ were recruited from the baseline study of Suwon Project (SP) between 2009 and 2011 (n=2040). Perceived sleep quality was measured using the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K), and depression was accessed using the Korean version of the Geriatric Depression Scale-Short Form (SGDS-K). We excluded the cognitively impaired elderly using the Korean version-Mini Mental Status Examination (K-MMSE) score less than or equal to 17. In multivariable adjusted logistic regression related to PSQI-K components, poor perceived sleep quality, including poor subjective sleep quality (Odds ratio (OR)=1.27, 95% confidence interval (CI)=1.01-1.61), longer sleep latency (OR=1.32, 95% CI=1.13-1.55) and the frequent use of sleeping medication (OR=1.30, 95% CI=1.10-1.53) were significantly associated with depression after adjusting for age, sex, education, living status, current smoking and current alcohol drinking, the number of comorbidity and Beck Anxiety Inventory (BAI). PSQI-K global score also had greater odds of reporting depression (OR=1.12, 95% CI=1.07-1.16). These results suggested that poor perceived sleep quality was associated with a greater level of depression in the elderly.

Perioperative psycho-educational intervention can reduce postoperative delirium in patients after cardiac surgery: a pilot study.

OBJECTIVE: Postoperative delirium after cardiac surgery is associated with many consequences such as poorer functional recovery, more frequent postoperative complications, higher mortality, increased length of hospital stay, and higher hospital costs. The aim of this study was to evaluate the efficacy of perioperative psycho-educational intervention in preventing postoperative delirium in post cardiac surgery patients. METHOD: We conducted a comparative retrospective study between 49 patients who had received perioperative psycho-educational intervention and 46 patients who had received standard care. The primary outcome was the incidence of postoperative delirium. Secondary outcomes included length of ICU stay, and severity and duration of postoperative delirium among the patients who had developed delirium. RESULTS: The incidence of postoperative delirium was significantly lower in the intervention group than that in the control group (12.24% vs. 34.78%, P = 0.009). Among the patients who had developed postoperative delirium, there was no statistical difference between the two groups regarding secondary outcomes. CONCLUSIONS: Our results show that the patients who received perioperative psycho-educational intervention were associated with a lower incidence of postoperative delirium after cardiac surgery than those who received standard care. Clinicians would be able to implement this psycho-educational intervention as part of routine practice to reduce delirium.

Concurrent administration of Neu2000 and lithium produces marked improvement of motor neuron survival, motor function, and mortality in a mouse model of amyotrophic lateral sclerosis.

The Fas pathway and oxidative stress mediate neuronal death in stroke and may contribute to neurodegenerative disease. We tested the hypothesis that these two factors synergistically produce spinal motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Levels of reactive oxygen species were increased in motor neurons from ALS mice compared with wild-type mice at age 10 weeks, before symptom onset. The proapoptotic proteins Fas, Fas-associated death domain, caspase 8, and caspase 3 were also elevated. Oral administration of 2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)-benzoic acid (Neu2000), a potent antioxidant, blocked the increase in reactive oxygen species but only slightly reduced activation of proapoptotic proteins. Administration of lithium carbonate (Li(+)), a mood stabilizer that prevents apoptosis, blocked the apoptosis machinery without preventing oxidative stress. Neu2000 or Li(+) alone significantly enhanced survival time and motor function and together had an additive effect. These findings provide evidence that jointly targeting oxidative stress and Fas-mediated apoptosis can prevent neuronal loss and motor dysfunction in ALS.

A distinct death mechanism is induced by 1-methyl-4-phenylpyridinium or by 6-hydroxydopamine in cultured rat cortical neurons: degradation and dephosphorylation of tau.

We examined whether the well-known neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium ion (MPP(+)) recruit distinct cell death mechanisms using primary cultured neurons derived from day 16 embryonic rat cortices. Electron microscopy revealed that cell death induced by both 6-OHDA and MPP(+) was typified by a condensation of chromatin while prominent mitochondrial swelling was observed only in those cells treated with MPP(+). Co-treatment of cells with a pan-caspase inhibitor, Z-VAD-fmk, attenuated 6-OHDA-induced chromatin condensation and neuronal death. Co-treatment with such antioxidants as N-acetylcysteine or Mn-TBAP also suppressed 6-OHDA-induced cell death. None of these treatments attenuated MPP(+)-induced cell death although caspase inhibition abolished MPP(+)-induced chromatin condensation. Interestingly, in these paradigms of cell death, the N-terminus of tau was specifically cleaved and the levels of phosphorylated tau were markedly decreased following 6-OHDA treatment. By contrast, the C-terminus of tau was cleaved in MPP(+)-induced cell death while the levels of phosphorylated tau remained largely unaltered. Taken together, our results indicate that distinct cellular mechanisms appear to underlie neurotoxin-induced cortical neuronal cell death.

Impaired D2 dopamine receptor function in mice lacking type 5 adenylyl cyclase.

Dopamine receptor subtypes D1 and D2, and many other seven-transmembrane receptors including adenosine receptor A2A, are colocalized in striatum of brain. These receptors stimulate or inhibit adenylyl cyclases (ACs) to produce distinct physiological and pharmacological responses and interact with each other synergistically or antagonistically at various levels. The identity of the AC isoform that is coupled to each of these receptors, however, remains unknown. To investigate the in vivo role of the type 5 adenylyl cyclase (AC5), which is preferentially expressed in striatum, mice deficient for the AC5 gene were generated. The genetic ablation of the AC5 gene eliminated >80% of forskolin-induced AC activity and 85-90% of AC activity stimulated by either D1 or A2A receptor agonists in striatum. However, D1- or A2A-specific pharmaco-behaviors were basically preserved, whereas the signal cascade from D2 to AC was completely abolished in AC5(-/-), and motor activity of AC5(-/-) was not suppressed by treatment of cataleptic doses of the antipsychotic drugs haloperidol and sulpiride. Interestingly, both haloperidol and clozapine at low doses remarkably increased the locomotion of AC5(-/-) in the open field test that was produced in part by a common mechanism that involved the increased activation of D1 dopamine receptors. Together, these results suggest that AC5 is the principal AC integrating signals from multiple receptors including D1, D2, and A2A in striatum and the cascade involving AC5 among diverse D2 signaling pathways is essential for neuroleptic effects of antipsychotic drugs.