Choroidal Proteins Involved in Cerebrospinal Fluid Production may be Potential Drug Targets for Alzheimer’s Disease Therapy

Alzheimer’s disease is known to be the most common form of dementia in the elderly. It is clinically characterized by impairment of cognitive functions, as well as changes in personality, behavioral disturbances and an impaired ability to perform activities of daily living. To date, there are no effective ways to cure or reverse the disease. Genetic studies of early-onset familial Alzheimer’s disease cases revealed causative mutations in the genes encoding β-amyloid precursor protein and the γ-secretase-complex components presenilin-1 and presenilin-2, supporting an important role of β-amyloid in the pathogenesis of Alzheimer’s disease. Compromised function of the choroid plexus and defective cerebrospinal fluid production and turnover, with diminished clearance of β-amyloid, may play an important role in late-onset forms of Alzheimer’s disease. If reduced cerebrospinal fluid turnover is a risk factor for Alzheimer’s disease, then therapeutic strategies to improve cerebrospinal fluid flow are reasonable. However, the role of deficient cerebrospinal fluid dynamics in Alzheimer’s disease and the relevance of choroidal proteins as potential therapeutic targets to enhance cerebrospinal fluid turnover have received relatively little research attention. In this paper, we discuss several choroidal proteins, such as Na+-K+ ATPase, carbonic anhydrase, and aquaporin 1, that may be targets for pharmacological up-regulation of cerebrospinal fluid formation. The search for potentially beneficial drugs useful to ameliorate Alzheimer’s disease by facilitating cerebrospinal fluid production and turnover may be an important area for future research. However, the ultimate utility of such modulators in the management of Alzheimer’s disease remains to be determined. Here, we hypothesize that caffeine, the most commonly used psychoactive drug in the world, may be an attractive therapeutic candidate for treatment of Alzheimer’s disease since long-term caffeine consumption may augment cerebrospinal fluid production. Other potential mechanisms of cognitive protection by caffeine have been suggested by recent studies

Increased Cerebrospinal Fluid Production as a Possible Mechanism Underlying Caffeine's Protective Effect against Alzheimer's Disease

Alzheimer's disease (AD), the most common type of dementia among older people, is characterized by the accumulation of β-amyloid (Aβ) senile plaques and neurofibrillary tangles composed of hyperphosphorylated tau in the brain. Despite major advances in understanding the molecular etiology of the disease, progress in the clinical treatment of AD patients has been extremely limited. Therefore, new and more effective therapeutic approaches are needed. Accumulating evidence from human and animal studies suggests that the long-term consumption of caffeine, the most commonly used psychoactive drug in the world, may be protective against AD. The mechanisms underlying the suggested beneficial effect of caffeine against AD remain to be elucidated. In recent studies, several potential neuroprotective effects of caffeine have been proposed. Interestingly, a recent study in rats showed that the long-term consumption of caffeine increased cerebrospinal fluid (CSF) production, associated with the increased expression of Na+-K+ ATPase and increased cerebral blood flow. Compromised function of the choroid plexus and defective CSF production and turnover, with diminished clearance of Aβ, may be one mechanism implicated in the pathogenesis of late-onset AD. If reduced CSF turnover is a risk factor for AD, then therapeutic strategies to improve CSF flow are reasonable. In this paper, we hypothesize that long-term caffeine consumption could exert protective effects against AD at least in part by facilitating CSF production, turnover, and clearance. Further, we propose a preclinical experimental design allowing evaluation of this hypothesis

Association of personality facets and cognition in the Lifelines population-based cohort study

Background: Personality traits have been associated with cognitive functioning and risk of cognitive decline. Fewer studies have investigated how personality facets are associated with cognition in large cohorts with a prospective design. Methods: The association between eight personality facets and cognition (speed measures reflecting psychomotor speed and visual attention; hit rate measures reflecting visual learning and working memory) was analyzed in middle-aged adults from the Lifelines cohort (N = 79911; age 43 ± 11 years). Results: High hostility, high vulnerability, low excitement seeking, and low competence were associated with worse cognitive performance on all tasks. Impulsivity-related facets had weak and differential associations, with self-discipline negatively associated with accuracy and deliberation negatively associated with speed. These associations remained largely unchanged when accounting for lifestyle factors (smoking, alcohol consumption, physical activity). The associations with cognition were stronger in older people for impulsiveness, deliberation, and hostility, while stronger in younger people for excitement seeking, self-discipline, and vulnerability. Conclusion: In a large population-based sample with a broad age range, the associations of personality facets with cognitive functioning had small effect sizes, were independent of lifestyle factors, and varied with age and among facets within the same personality domain. These findings highlight the importance of developmental stages and facet-level research in personality-cognition associations.</p

The 10-word learning task in the differential diagnosis of early Alzheimer's disease and elderly depression: a cross-sectional pilot study

Objectives: Identification of early Alzheimer's disease (AD) has become very important. Episodic memory tasks appear to have predictive power for indicating early AD. Deficits in encoding and storage processes that are characteristic of AD, however, must be distinguished from non-AD deficits that can also affect memory, including difficulties that may be present in depression. This pilot study was set up to ascertain whether a 10-word-list-learning task (delayed recognition and rate of forgetting) may be useful in making the differentiation between mild AD and depression. Method: A Dutch version of Rey's auditory verbal learning test was administered to 36 mild AD patients, 41 depressed patients, and 47 healthy controls. Data were analyzed in a cross-sectional manner. Results: Receiver operating characteristic analyses showed that for differentiating mild AD and depression, both delayed recognition and percentage of forgetting have sufficient diagnostic accuracy. Conclusion: Percentage of forgetting had the highest diagnostic accuracy for differentiating mild AD and depressed patients and may be useful in the early detection of AD

SCIENTIFIC METHOD ONPRODUCTION PROCESS ASANEFFORTTOIMPROVE REAL SECTORS CONTRIBUTION TO THE INDONESIAN ECONOMY

Economic condition of Indonesia at presents, requires a positive contribution from all economic perpetrators in Indonesia, especially from real sectors. This sector becomes important because most company assets invested in this real sector activity, as well as the number of human resources. With this condition, this research aims at analyzing the application of scientific production method in real sector production activity, so that obtain information how far production activity conducted with scientific method, and how perpetrators concerned with this matter. This research was conducted with real sector as the sample in Depok and Bogor region. Analysis was done using descriptive and inferential analyses dealing with the data of the questionnaires administered. Temporary result shows that most respondents, although getting support from management (36%), the practice shows that not all respondents applied scientific production method in their production activity. Consequently, the production is not optimum. The cause was that technological aspect were not adequate due to the support of the management could not be fully realized. For example, less development time allocation and less supply of production technology infrastructure. In conclusion, this is quiet irony because real sectors are expected to have a positive contribution to the development of Indonesian economy, while the real condition of real sectors does not apply scientific method optimally yet