Objective The cholinergic system has an important role in attention and working memory and patients with Alzheimer’s Disease (AD) are known to have cholinergic disruption. Acetylcholinesterase Inhibitors (AChEIs), such as donepezil and rivastigmine, increase attention and working memory functioning, but no investigations have directly compared these medications. Method We compared groups of patients with AD taking either donepezil, rivastigmine, or no AChEI on several measures of attention and working memory. Results The results consistently indicated better attention and working memory functioning in patients taking donepezil. Conclusion Hence, donepezil seems to have more of a positive impact on attention and working memory. These results may have important implications for the treatment of disorders characterized by problems with attention functioning, such as Lewy body dementia.

Alzheimer’s disease is the most common cause of age-dependent cognitive decline composing a tragic epilogue in senility. A substantial number of cellular and biochemical mechanisms contribute in shaping the multifactorial pathogenetic background of the disease. In the neuropathological profile of Alzheimer’s disease, selective neuronal loss [1], synaptic alterations [2], tau pathology [3], extracellular deposits of polymers of Aß peptide [4], inflammatory responses [5] and morphological alterations of the cell organelles [6] are the most common phenomena in light and electron microscopy.

Background Cognitive screening for elderly patients with mild dementia is typically conducted in the morning under the impression that testing at this time will optimize performance and cooperation of patients. This study was conducted to determine if the time of day in which several cognitive screening tests would be normally given could significantly affect test performance in patients with mild dementia and normal control subjects. Methods Fifty nursing home residents with mild to moderate dementia and twenty normal control subjects were given three commonly used cognitive tests in two separate sessions (morning and afternoon) with a two week interval between sessions. Half of subjects were tested first in the morning and second in the afternoon, the other half first in the afternoon and second in the morning. Evaluation tools included the Mini Mental Status Exam (MMSE), the Mini-Cog Test, and Semantic Verbal Fluency (for animal names) at each session. Test scores were compared within each subject between the morning and afternoon sessions. Results Across all subjects, better scores were observed for afternoon performance in the MMSE score (p<0.005) and Mini-Cog (p<0.011) for subjects who tested first in the morning and second in the afternoon. No differences were observed in the reverse condition. The morning/afternoon differences and trends across all subjects were strongest for the mild dementia group (MMSE, p<0.003; Mini-Cog, p<0.075). However, the analysis also indicated that test experience contributed to some of the observed differences, such that no clear effect of time of day on performance could be substantiated. Conclusion Under the conditions of this study, we could not conclude that performance on cognitive tests was significantly affected by the time of day of administration. A more comprehensive study will be necessary to better define the potential factors identified.

Introduction: The use of a standardized program, designed by a music therapist, for cognitively impaired adults to improve well-being and attenuate cognitive decline. Methods: An experimental control group study with eight participants for 26 weekly sessions. Mental status, level of depression, quality of life, and caregiver burden were measured prior to and following completion of the study. Quality of life was achieved as measured by a process evaluation. Results: The study participants experienced less cognitive decline and depression when compared to the control group. There was no difference in caregiver burden among both groups. Discussion: Participation in a mutual support group using music therapy may diminish cognitive decline and depression.

Introduction: The use of a standardized program, designed by a music therapist, for cognitively impaired adults to improve well-being and attenuate cognitive decline. Methods: An experimental control group study with eight participants for 26 weekly sessions. Mental status, level of depression, quality of life, and caregiver burden were measured prior to and following completion of the study. Quality of life was achieved as measured by a process evaluation. Results: The study participants experienced less cognitive decline and depression when compared to the control group. There was no difference in caregiver burden among both groups. Discussion: Participation in a mutual support group using music therapy may diminish cognitive decline and depression.

Alzheimer’s Disease (AD) diagnosis frequently relies on patient’s cognitive evaluation deficits and exclusion criteria often implemented in advanced stages of dementia, when it is too late for effective therapeutic intervention. In order to improve early AD diagnosis and therapeutic interventions, novel approaches for AD biomarker identification and validation need to be developed. These comprise metabolomics based strategies, including Fourier Transform Infrared Spectroscopy (FTIR) that has gained increasing attention in the clinical diagnostics field. The present work aims to contribute to identify the main metabolic changes that occur during neurodegeneration, by monitoring plasma biochemical alterations that can aid in dementia/cognitive impairment diagnosis, through FTIR analysis. Principal Component Analysis (PCA) was applied to spectral data (45 plasma samples) at 3 specific regions: 3500-2700 cm-1, 1700-1400 cm-1 and 1200-900 cm-1. Plasma samples from cognitive impaired individuals exhibit the presence of higher content of saturated lipids, carboxylic acids, reactive carbonyls, and other molecules related to oxidative stress (ROS and NOS species), and protein modifications. Taken together the data obtained in this preliminary work strongly supports that FTIR has potential in diagnosing cognitive impairment, identification of disease states and may prove to also be of prognostic value.

Rensheng Shouwu Capsule (RSSW) is an approved and patented drug of Traditional Chinese Medicine that has been used for years to treat vascular dementia and neural syndrome related to cerebral-vascular ischemia. However, the underlying mechanism of RSSW remains unclear. Previous studies have indicated that RSSW could significantly reduce cerebral ischemic injury and improve vascular dementia. In the present study, cultured cortical neuron hypoxia/reoxygenation injury model was used to test the neuroprotection of RSSW and its mechanisms in vitro. RSSW 0.2~5.0 µg/ml was demonstrated to increase intracellular endogenous superoxide dismutase, restore the level of mitochondrial membrane potential in hypoxia/anoxia-injured neurons in a dose-dependent manner. RSSW was also shown to inhibit neuronal apoptosis dose-dependently by suppressing the activity of caspase 3 and caspase 9 and by decreasing the level of reactive oxygen species, the leak of lactate dehydrogenase and the accumulation of malondialdehyde, in hypoxia/anoxia-injured neurons. These findings suggest that the neuroprotection of RSSW from hypoxia injuries may be related to the improvement of intracellular endogenous antioxidants, and the inhibition of the caspase 3 and caspase 9 expression, which might represent the mechanisms underlying RSSW prevention and treatment of neurodegenerative disorders and neural disorders related to cerebral-vascular ischemia.

Networks of signaling cascades regulate synaptic transmission and morphology. Signaling molecules and their dynamics are subject to impact of environmental insults as well as genes predisposing to disease risks. Pollutants may impact brain through cellular, molecular and inflammatory pathways, causing direct damage or predisposing to damage by other insults, leading to diseases. Disruptions in structure and function of neurotransmission elements and protein networks contribute to pathogenesis of neuropsychiatric diseases. Different affected brain regions and/or synaptic connections between excitatory and inhibitory neurons charecterise specific clinical states. Functional identification of synaptic signaling networks and specific neuronal pathways would facilitate understanding of specific pathomechanisms relevant to preventive and corrective interventions. Physiology of neural networks and pathogenesis, therapeutics and prevention of diseases arising of their disruption, specially with environmental afflictions, deserve holistic and not fragmentary understanding. Present article attempts to present such diverse information with possible coherence to emphasize necessary address in contemporary medical teaching and continuing education for young researchers. The mounting challenge of prevention and management of pollution inflicted disruption of neurophysiology associated with brain dysfunction and diseases in contemporary world may be better addressed by integrated interdisciplinary understanding of the problems.

Over the time, it is becoming clear that microtubule system plays a fundamental role not only during the development of central nervous system but also during brain aging and neuronal death. In particular, the fine modulation of microtubule stability and tubulin posttranslational modifications is crucial for neurons as its failure induces brain damage. Basing our idea on the facts that dopaminergic neurons possess a peculiar architecture, strictly dependant on microtubule integrity, and that most of the experimental models of Parkinson’s disease undergo microtubule destabilization before dopaminergic cells loss, here we propose that the regulation of microtubule stability can be the Achilles’ heel of this neuronal population. Therefore, we hypothesize that failure of the modulation of microtubule system could represent the crossroad between normal brain aging and neurodegenerative processes.

Because humans have a long lifespan relative to other organisms, aging studies have been performed in a variety of systems. Caenorhabditis elegans (C. elegans) is one model organism that has been used to study aging due to its short life span (about 3 weeks), low cost for maintenance, its ease of cultivation and the fact that it produces large number of offspring [1-2]. The mechanisms involved in aging in C. elegans have also been studied in other organisms, including mammals. Among these mechanisms are oxidative damage, dietary restriction, reduction in the Insulin/Insulin-like Growth Factor (IGF) signaling pathway and decreased TOR (Target of Rapamycin) signaling [1-4].

Background Alzheimer’s Disease (AD) is characterized by deposition of amyloid plaques of amyloid-ß chelating peptide with transition metal ions (Cu2+, Zn2+ and Fe3+). The binding of Cu2+ and Fe3+ leads to toxic chemical reactions; a change in the oxidation of two metals, that leads to H2O2 production in the presence of transition metals and finally gives toxic free OH• radicals. Methods 58 Alzheimer’s disease patients were included in this study. They were evaluated for serum iron, copper, selenium, zinc and hepcidin levels. Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPX) were measured as oxidative stress markers. Hepcidin, SOD and GPX were measured by ELISA methods. Serum Fe, Cu, Se and Zn were quantified by AAS. The results form AD patients were compared to age and gender matched healthy controls. We used Pearson’s correlation and Student’s paired t-test for statistical analysis of established results. Results We found statistically significant elevated serum iron, copper and zinc results in AD patients (41.4 µmol/l, 37.8 µmol/l, and 39.9 µmol/l) compared to control group (20.6 µmol/l, 19.1 µmol/l, and 14.8 µmol/l); P<0.01. Plasma selenium levels were decreased in AD patients (114.8 nmol/L) compared to healthy controls (629.6 nmol/L); P<0.005. Hepcidin concentrations were increased in AD cases (64.9 µg/l) compared to controls (22.3 µg/l); P<0.001. SOD and GPX levels were decreased in Alzheimer’s disease (8.1 µg/ml, and 10.5 pg/mL) compared to normal values in healthy controls (20.4 µg/ml, and 37.4 pg/mL); P<0.001. Conclusions The expected contribution from our study is practical introduction of quantification of serum hepcidin as a potential marker for early diagnosis of impaired iron homeostasis, leading trace element in the pathogenesis of neurodegenerative diseases.

Introduction: Due to a significant rise in the ageing population and an associated rise in the prevalence of dementia; there are inevitable pressures on hospital staff to provide safe, person-centered dementia care. The National Dementia Audit (2012-13) reported a lack of appropriate dementia care, which could be due to lack of awareness and training during medical school or during early stages of professional training. The objective of this study was to determine medical students’ and doctors’ attitudes towards older people with dementia and evaluate the impact of a structured dementia training workshop. Method: A consultant led workshop lasting one and a half hours was delivered to 201 year-4 medical students and Foundation Year (FY) doctors over a three year period. Each session included an introductory talk on dementia, two group workshop activities and a video showing patients and their family members’ perspectives on dementia. We used the 14-item University of California, Los Angeles (UCLA) Geriatrics Attitudes Scale (GAS) and the 17-item Sense of Competence in Dementia Care Staff (SCIDS) scale pre- and post-training to measure perceived changes in attitude to and competence in managing patients with dementia. Results: A total of 173 questionnaires were completed pre-training out of a cohort of 201 (response rate 86.1%) and 167 were completed post-training (response rate 96.5%). The overall pre-training mean UCLA GAS score was 3.77 ± 0.48 suggesting a generally positive attitude towards patients with dementia. There was no significant change in the mean UCLA GAS score following the dementia training. The overall pre-training mean SCIDS score was 2.42 ± 0.40 and we found there was a significant change in the perceived competence in dementia care following the training. The overall feedback was positive and all trainee doctors suggested that this dementia training will help them to improve their communication with patients, families and staff and they will encourage multidisciplinary approach whilst managing challenges associated with dementia. Conclusion: Dementia specific training workshop did not show any significant changes in medical students or FY doctors attitudes towards patients with dementia. However, there was a significant improvement in perceived competence in caring for patients with dementia amongst the group. This would suggest an increase in knowledge leads to development of practical approaches and coping strategies when providing dementia care. We propose that dementia training should be a vital part of the under-graduate medical school curriculum and post-graduate foundation or generic training in order to meet the challenges of healthcare delivery for the aging population

Due to the differences present between dementia patients and caregivers in Low and Middle Income Countries (LMICs) and in high income western societies, contextualized dementia research has been widely done in the last decade. Pakistan is also an LMIC with very limited research related to dementia. This study was a pilot survey among the attendees of a dementia awareness session held at the Aga Khan University Hospital in Karachi, Pakistan. A self-reported questionnaire was used to find out about the most distressful and frequent symptoms of dementia, care arrangement, and knowledge about the diagnosis. Out of the 38 participants who returned filled questionnaires, about half identified the type of dementia as “Alzheimer’s” and the other half was not aware of the type. Memory loss was reported as the most prominent and most distressing symptom by all patients and caregivers followed by anger/aggression and low mood/anxiety. Two thirds of patients/caregivers reported that patients engaged in hobbies or activities and “watching TV” was reported as the most common activity while “exercise” and “listening to music” were reported by the least number of people. Almost all caregivers identified themselves as primary caregivers, reported living in the same house with the patient and bearing the financial cost of care. Half of them were children of patients with dementia. One third of all participants reported having paid help. About 50% of all participants reported the activity as helpful and showed willingness to participate in such activities in future. The results from this study provide important insight into patient’s symptoms and knowledge about dementia as well care arrangement in Pakistan and has important implications for health care providers in managing patients and their families as well as in designing customized programs and policies.

Soluble, secreted Amyloid Precursor Protein-a (sAPPa), a product of a-secretase (ADAM10) cleavage of Full Length-APP (FL-APP), is a trophic factor critical for synaptic complexity and maintenance. As cleavage at the a-site of APP precludes the ß-site cleavage that is the first step in Amyloid ß (Aß) production, enhancing sAPPa production may not only support and restore neuronal health, but may also decrease the generation of anti-trophic Aß. Over-production or reduced clearance of Aß is a hallmark of Alzheimer’s Disease (AD), and recent findings suggest it also plays a role in other neurodegenerative diseases and neurological conditions, such as Amyotrophic Lateral Sclerosis (ALS), Cerebral Amyloid Angiopathy (CAA), and Traumatic Brain Injury (TBI). Yet decades of focus on Aß-lowering strategies alone including passive and active immunotherapy and ?-secretase and BACE1 (BACE) inhibition have yet to yield positive clinical results. Clinical trials of several BACE inhibitors are underway in AD patients, and although there is optimism about this strategy, there are also concerns about mechanism-based side-effects of these drugs. A truly effective therapy would not only slow the degenerative process underlying onset and progression of the disease, it should also restore healthy neuronal function. It is very likely this will comprise combination therapy utilizing more than one drug or intervention. Molecules that enhance sAPPa may be a safe, effective component of a multi-modal therapeutic approach to AD and other neurodegenerative diseases, and have the potential to increase neuronal health by providing trophic support and disrupting neurodegenerative mechanisms.