Alzheimer's Disease Medications Research Articles

No Evidence to Suggest that the Use of Acetylcholinesterase Inhibitors Confounds the Results of Two Blood-Based Biomarker Studies in Alzheimer's Disease.

There is an urgent need to discover Alzheimer's disease (AD) biomarkers that are both easily measured and reliable. Research into blood-based biomarkers for AD using transcriptomics and proteomics has been an attractive and promising area of research. However, to date researchers have not looked into the possibility of AD medication being a confounding factor in these studies. This study explored whether acetylcholinesterase inhibitors (AChEIs), the main class of AD medication, are a confounding factor in AD blood biomarker studies. The most promising blood transcriptomic and proteomic biomarkers from two recent studies were analyzed to determine if they were differentially expressed between AD subjects on AChEIs and subjects that were not. None of the gene or protein biomarkers analyzed were found to be significantly altered between subjects in either group. This study found no evidence that AChEIs are a confounding factor in these published AD blood biomarker studies. Further work is needed to confirm that this is also the case for other proposed biomarkers.

Tolerability and safety of Souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study.

The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs. In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated. Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter. Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention. Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT.

An updated Alzheimer's disease progression model: incorporating non-linearity, beta regression, and a third-level random effect in NONMEM.

Our objective was to expand our understanding of the predictors of Alzheimer's disease (AD) progression to help design a clinical trial on a novel AD medication. We utilized the Coalition Against Major Diseases AD dataset consisting of control-arm data (both placebo and stable background AD medication) from 15 randomized double-blind clinical trials in mild-to-moderate AD patients (4,495 patients; July 2013). Our ADAS-cog longitudinal model incorporates a beta-regression with between-study, -subject, and -residual variability in NONMEM; it suggests that faster AD progression is associated with younger age and higher number of apolipoprotein E type 4 alleles (APOE*4), after accounting for baseline disease severity. APOE*4, in particular, seems to be implicated in the AD pathogenesis. In addition, patients who are already on stable background AD medications appear to have a faster progression relative to those who are not receiving AD medication. The current knowledge does not support a causality relationship between use of background AD medications and higher rate of disease progression, and the correlation is potentially due to confounding covariates. Although causality has not necessarily been demonstrated, this model can inform inclusion criteria and stratification, sample size, and trial duration.

The use of medications approved for Alzheimer's disease in autism spectrum disorder: a systematic review.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects 1 in 68 children in the United States. Even though it is a common disorder, only two medications (risperidone and aripiprazole) are approved by the U.S. Food and Drug Administration (FDA) to treat symptoms associated with ASD. However, these medications are approved to treat irritability, which is not a core symptom of ASD. A number of novel medications, which have not been approved by the FDA to treat ASD have been used off-label in some studies to treat ASD symptoms, including medications approved for Alzheimer’s disease. Interestingly, some of these studies are high-quality, double-blind, placebo-controlled (DBPC) studies. This article systematically reviews studies published through April, 2014, which examined the use of Alzheimer’s medications in ASD, including donepezil (seven studies, two were DBPC, five out of seven reported improvements), galantamine (four studies, two were DBPC, all reported improvements), rivastigmine (one study reporting improvements), tacrine (one study reporting improvements), and memantine (nine studies, one was DBPC, eight reported improvements). An evidence-based scale was used to rank each medication. Collectively, these studies reported improvements in expressive language and communication, receptive language, social interaction, irritability, hyperactivity, attention, eye contact, emotional lability, repetitive or self-stimulatory behaviors, motor planning, disruptive behaviors, obsessive–compulsive symptoms, lethargy, overall ASD behaviors, and increased REM sleep. Reported side effects are reviewed and include irritability, gastrointestinal problems, verbal or behavioral regression, headaches, irritability, rash, tremor, sedation, vomiting, and speech problems. Both galantamine and memantine had sufficient evidence ranking for improving both core and associated symptoms of ASD. Given the lack of medications approved to treat ASD, further studies on novel medications, including Alzheimer’s disease medications, are needed.

Potential of bone marrow mesenchymal stem cells in management of Alzheimer's disease in female rats.

Alzheimer's disease (AD) has been called the disease of the century with significant clinical and socioeconomic impacts. Pharmacological treatment has limited efficacy and only provides symptomatic relief without long-term cure. Accordingly, there is an urgent need to develop novel and effective medications for AD. Stem cell-based therapy is a promising approach to handling neurodegenerative diseases. Therefore, the current study aimed to explore the possible therapeutic role of single intravenous injection of bone marrow derived mesenchymal stem cells (BM-MSCs) after 4 months in management of AD in the experimental model. The work also extended to compare the therapeutic potential of BM-MSCs with 2 conventional therapies of AD; rivastigmine and cerebrolysin administered daily. BM-MSCs were able to home at the injured brains and produced significant increases in the number of positive cells for choline acetyltransferase (ChAT) and survivin expression, as well as selective AD indicator-1 (seladin-1) and nestin gene expression. Histopathological examination indicated that BM-MSCs could remove beta-amyloid plaques from hippocampus. Significant improvement in these biomarkers was similar to or better sometimes than the reference drugs, clearly showing the potential therapeutic role of BM-MSCs against AD through their anti-apoptotic, neurogenic and immunomodulatory properties.

Dihydromyricetin ameliorates behavioral deficits and reverses neuropathology of transgenic mouse models of Alzheimer's disease.

Alzheimer's disease (AD) is the leading progressive neurodegenerative disorder afflicting 35.6 million people worldwide. There is no therapeutic agent that can slow or stop the progression of AD. Human studies show that besides loss of cognition/learning ability, neuropsychological symptoms such as anxiety and seizures are seen as high as 70 and 17% respectively in AD patients, suggesting dysfunction of GABAergic neurotransmission contributes to pathogenesis of AD. Dihydromyricetin (DHM) is a plant flavonoid and a positive allosteric modulator of GABAARs we developed recently (Shen et al. in J Neurosci 32(1):390-401, 2012 [1]). In this study, transgenic (TG2576) and Swedish transgenic (TG-SwDI) mice with AD-like pathology were treated with DHM (2mg/kg) for 3months. Behaviorally, DHM-treated mice show improved cognition, reduced anxiety level and seizure susceptibility. Pathologically, DHM has high efficacy to reduce amyloid-β (Aβ) peptides in TG-SwDI brain. Further, patch-clamp recordings from dentate gyrus neurons in hippocampal slices from TG-SwDI mice showed reduced frequency and amplitude of GABAAR-mediated miniature inhibitory postsynaptic currents, and decreased extrasynaptic tonic inhibitory current, while DHM restored these GABAAR-mediated currents in TG-SwDI. We found that gephyrin, a postsynaptic GABAAR anchor protein that regulates the formation and plasticity of GABAergic synapses, decreased in hippocampus and cortex in TG-SwDI. DHM treatment restored gephyrin levels. These results suggest that DHM treatment not only improves symptoms, but also reverses progressive neuropathology of mouse models of AD including reducing Aβ peptides, while restoring gephyrin levels, GABAergic transmission and functional synapses. Therefore DHM is a promising candidate medication for AD. We propose a novel target, gephyrin, for treatment of AD.

Kidney Function and Prevalent and Incident Frailty

Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants. CHS enrolled community-dwelling adults age ≥65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity. The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) ≥90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty. In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function.

Discovering New Treatments for Alzheimer's Disease by Repurposing Approved Medications

Alzheimer's disease (AD) is the most common cause of dementia and a major cause of morbidity and mortality. The greatest risk factor for AD is age and as many countries are experiencing an aging population, the expected rise in AD threatens to have serious medical and socioeconomic impact in the coming decades. The only approved medications for AD are symptomatic and there are no currently available disease modifying treatments. Hence, a disease modifying treatment is desperately needed for AD not only for proper care and management of affected patients, but also to reduce society's socioeconomic burden. Developing novel compounds for any indication is a time, effort, and money consuming endeavor and most treatments never make it to market. Other research and development strategies are needed, especially for the treatment of AD. We provide a review of the current literature in assessing possibilities of repurposing medications currently used for non-AD indications. Many different compounds from many different pharmacological classes have already been studied in an AD context. We provide a "pragmatic drug repurposing score" for each of these compounds based on type of studies conducted, number of possible mechanisms of action, efficacy in AD and other neurodegenerative disease studies, tolerability profile, and their ability to cross the blood brain barrier. The current data suggest several compounds worthy of further study as treatments for AD. Compounds with the highest scores include lithium, minocycline, exenatide, valproic acid, methylene blue, and nicotine.

The Impact of AD Drug Treatments on Event-Related Potentials as Markers of Disease Conversion

This paper investigates how commonly prescribed pharmacologic treatments for Alzheimer's disease (AD) affect Event-Related Potential (ERP) biomarkers as tools for predicting AD conversion in individuals with Mild Cognitive Impairment (MCI). We gathered baseline ERP data from two MCI groups (those taking AD medications and those not) and later determined which subjects developed AD (Convert->AD) and which subjects remained cognitively stable (Stable). We utilized a previously developed and validated multivariate system of ERP components to measure medication effects among these four subgroups. Discriminant analysis produced classification scores for each individual as a measure of similarity to each clinical group (Convert->AD, Stable), and we found a large significant main Group effect but no main AD Medications effect and no Group by Medications interaction. This suggested AD medications have negligible influence on this set of ERP components as weighted markers of disease progression. These results provide practical information to those using ERP measures as a biomarker to identify and track AD in individuals in a clinical or research setting.

History of Medically Treated Diabetes and Risk of Alzheimer Disease in a Nationwide Case-Control Study

OBJECTIVEType 2 diabetes in midlife or late life increases the risk of Alzheimer disease (AD), and type 1 diabetes has been associated with a higher risk of detrimental cognitive outcomes, although studies from older adults are lacking. We investigated whether individuals with AD were more likely to have a history of diabetes than matched controls from the general aged population.RESEARCH DESIGN AND METHODSInformation on reimbursed diabetes medication (including both type 1 and 2 diabetes) of all Finnish individuals with reimbursed AD medication in 2005 (n = 28,093) and their AD-free control subjects during 1972–2005 was obtained from a special reimbursement register maintained by the Social Insurance Institute of Finland.RESULTSThe prevalence of diabetes was 11.4% in the whole study population, 10.7% (n = 3,012) among control subjects, and 12.0% (n = 3,372) among AD case subjects. People with AD were more likely to have diabetes than matched control subjects (unadjusted OR 1.14 [95% CI 1.08–1.20]), even after adjusting for cardiovascular diseases (OR 1.31 [1.22–1.41]). The associations were stronger with diabetes diagnosed at midlife (adjusted OR 1.60 [1.34–1.84] and 1.25 [1.16–1.36] for midlife and late-life diabetes, respectively).CONCLUSIONSIndividuals with clinically verified AD are more likely to have a history of clinically verified and medically treated diabetes than the general aged population, although the difference is small.

Patients’ Willingness-to-Pay for an Alzheimer’s Disease Medication in Canada

Alzheimer's disease (AD) is a neurodegenerative disorder highlighted by progressive declines in cognition and function. The aim of this article is to assess whether persons with AD would support out-of-pocket payment for an AD medication; to elicit the monthly dollar amounts they would pay. We recruited persons with mild or moderate AD (n = 216) from nine clinics across Canada. During one-on-one interviews, we presented our sample with four scenarios describing a medication that either treated disease symptoms or modified the course of AD; each version of the medication was alternatively presented as having a 0 % or 30 % chance of adverse effects. For each scenario, participants indicated whether they would support paying out-of-pocket for the medication (yes/no). Affirmative responses were followed with questions asking participants whether they would pay $75, $150, or $225 (Canadian dollars) per month. Levels of support ('yes' responses) ranged from 57 % to 83 % and mean willingness-to-pay ranged from $98 to $137, depending on scenario. Participants were more likely to provide affirmative responses and higher willingness-to-pay amounts when the medication modified disease or had a 0 % chance of adverse effects. Age was inversely associated with support in three scenarios and willingness-to-pay amounts in all four scenarios. Positive associations between post-secondary education and willingness-to-pay amounts were found in three scenarios. Persons with mild or moderate AD were often willing to pay out-of-pocket for AD medications. However, the mean maximum willingness-to-pay ($137) for the optimal medication scenario was lower than the average monthly cost of existing AD medications.

The clinical and economic burden of newly diagnosed Alzheimer's disease in a medicare advantage population.

Alzheimer's disease (AD) represents a serious public health issue affecting approximately 5.4 million individuals in the United States and is projected to affect up to 16 million by 2050. This study examined health care resource utilization (HCRU), costs, and comorbidity burden immediately preceding new diagnosis of AD and 2 years after diagnosis. This study utilized a claims-based, retrospective cohort design. Medicare Advantage members newly diagnosed with AD (n = 3374) were compared to matched non-AD controls (n = 6748). All patients with AD were required to have 12 months of continuous enrollment prior to AD diagnosis (International Classification of Diseases, Clinical Modification [ICD-9] 331.0), during which time no diagnosis of AD, a related dementia, or an AD medication was observed. Non-AD controls demonstrated no diagnosis of AD, a related dementia, or a prescription claim for an AD medication treatment during their health plan enrollment. Medical and pharmacy claims data were used to measure HCRU, costs, and comorbidity burden over a period of 36 months (12 months pre-diagnosis and 24 months post-diagnosis). The HCRU and costs were greater for AD members during the year prior to diagnosis and during postdiagnosis years 1 and 2 compared to controls. The AD members also displayed greater comorbidity than their non-AD counterparts during postdiagnosis years 1 and 2, as measured by 2 different comorbidity indices. Members newly diagnosed with AD demonstrated greater HCRU, health care costs, and comorbidity burden compared to matched non-AD controls.

Current Alzheimer's Medications: Effective Treatment Options, or Expensive Bottles of Hope?

I am not a medical researcher, nor am I a medical doctor. I am, however, a spouse caregiver for my wife, who is now in moderate stages of Alzheimer disease (AD). My reading of the AD literature, my listening to other spouse caregivers, and my research on the effectiveness of current AD medications all tell me that doctors too often recommend that patients with AD continue taking ineffective “treatment medications.” Well after the time period when even the pharmaceutical manufacturers claim that their products are effective, many doctors continue to prescribe these same ineffective AD medications for their patients.

A population-based study of dosing and persistence with anti-dementia medications

Cholinesterase inhibitors and memantine are the mainstay of pharmacological intervention for the cognitive symptoms of Alzheimer's disease (AD). This study assessed the adequacy of dosing and persistence with AD medications and the predictors of these variables in the 'real world' (outside the clinical trial setting). The Health Service Executive-Primary Care Reimbursement Services prescription claims database in the Republic of Ireland contains prescription information for 1.6 million people. Patients aged >70 years who received at least two prescriptions for donepezil, rivastigmine, galantamine and memantine between January 2006 and December 2010 were included in the study. Rates of dose-maximisation were recorded by examining the initiation dose of each AD drug commenced during the study period and any subsequent dose titrations. Non-persistence was defined by a gap in prescribing of more than 63 consecutive days. Predictors of dose-maximisation and non-persistence were also analysed. Between January 2006 and December 2010, 20,729 patients aged >70 years received a prescription for an AD medication. Despite most patients on donepezil and memantine receiving a prescription for the maximum drug dose, this dose was maintained for 2 consecutive months in only two-thirds of patients. Patients were significantly more likely to have their doses of donepezil and memantine maximised if prescribed in more recent years (2010 vs. 2007). Rates of non-persistence were 30.1 % at 6 months and 43.8 % at 12 months. Older age [75+ vs. <75 years; hazards ratio (HR) 1.16, 95 % confidence interval (CI) 1.06-1.27] and drug type (rivastigmine vs. donepezil; HR 1.15, 95 % CI 1.03-1.27) increased the risk of non-persistence. Non-persistence was lower for those commencing therapy in more recent years (2010 vs. 2007; HR 0.81, 95 % CI 0.73-0.89, p < 0.001) and for those on multiple anti-dementia medications (HR 0.59, 95 % CI 0.54-0.65, p < 0.001). Persistence was significantly higher when memantine was co-prescribed with donepezil (p < 0.0001). Future studies should explore the reasons underlying non-persistence and failure to maintain dose-maximisation in patients on AD medications. There may be scope to improve the dosing and persistence with these medications in the community.

The General Publicʼs Willingness to Pay for Tax Increases to Support Unrestricted Access to an Alzheimerʼs Disease Medication

Alzheimer's disease (AD) is a neurodegenerative disorder highlighted by progressive declines in cognitive and functional abilities. Our objective was to assess the general public's maximum willingness to pay ((M)WTP) for an increase in annual personal income taxes to fund unrestricted access to AD medications. We randomly recruited 500 Canadians nationally and used computer-assisted telephone interviewing to administer a questionnaire. The questionnaire contained four 'efficacy' scenarios describing an AD medication as capable of symptomatically treating cognitive decline or modifying disease progression. The scenarios also described the medication as having no adverse effects or a 30% chance of adverse effects. We randomized participants to order of scenarios and willingness-to-pay bid values; (M)WTP for each scenario was the highest accepted bid for that scenario. We conducted linear regression and bootstrap sensitivity analyses to investigate potential determinants of (M)WTP. Mean (M)WTP was highest for the 'disease modification/no adverse effects' scenario ($Can130.26) and lowest for the 'symptomatic treatment/30% chance of adverse effects' scenario ($Can99.16). Bootstrap analyses indicated none of our potential determinants (e.g. age, sex) were associated with participants' (M)WTP. The general public is willing to pay higher income taxes to fund unrestricted access to AD (especially disease-modifying) medications. Consequently, the public should favour placing new AD medications on public drug plans. As far as we are aware, no other study has elicited the general public's willingness to pay for AD medications.

Attitudes toward Alzheimer’s disease: a qualitative study of the role played by social representation on a convenient sample of French general practitioners

It is commonly thought that Alzheimer's disease (AD) is under-diagnosed and that insufficient numbers of patients are receiving pharmacological treatment. These observations are often attributed to poor management of the disease by general practitioners (GPs) related to their lack of training in identifying cognitive decline. Our hypothesis is that there may be a relation between GPs' perceptions and their attitudes toward AD. We conducted a qualitative study, through semi-directive interviews focusing on their representations, of 25 GPs, masters in training courses, in Paris. Analysis of interviews revealed five general trends. AD is seen by GPs as a "disease of autonomy", without specific medical treatment. Cognitive symptoms are less meaningful in GPs' view than the loss of autonomy. The main thing is to keep the patient at home. For GPs, the family is described as an essential partner in coping with the insufficiencies of available social programs. The use of specialists is less to confirm the diagnosis than to announce the "bad news". GPs declare scepticism as to the efficacy of AD medications, only granting them a certain "care" effect or a social role. The image of AD remains highly negative. The stigma of AD is seen as a barrier to its diagnosis. This study is somewhat preliminary because of sample size. Nevertheless, the social representations of the disease influence GPs' attitudes toward making diagnoses in France. Priority seems to focus more on assisting GPs and families at the social level, rather than diagnosis or access to treatment.

Diagnosis and Management of Behavioral Issues in Frontotemporal Dementia

Frontotemporal lobar degeneration is an umbrella term for several different disorders. In behavioral variant frontotemporal dementia (bvFTD), patients show deterioration in cognition and social behavior. New diagnostic criteria proposed by the International Behavioral Variant FTD Consortium provide greater sensitivity in diagnosing bvFTD. Current pharmacological management of symptoms relies on medications borrowed from treating Alzheimer's disease (AD) and psychiatric disorders. The evidence for using AD medications such as acetylcholinesterase inhibitors is questionable. Psychiatric medications can be helpful. Trazodone or SSRIs can have some efficacy in reducing disinhibition, repetitive behaviors, sexually inappropriate behaviors, and hyperorality. Small doses of atypical antipsychotics may be helpful in decreasing agitation and verbal outbursts. Nonpharmacological management includes caregiver education and support and behavioral interventions. While symptomatic treatments are likely to remain important behavior management tools, targeting the underlying pathology of bvFTD with disease-modifying agents will hopefully be the future of treatment.

Economic Evaluation of Treatment Options in Patients with Alzheimerʼs Disease

Alzheimer's disease (AD) is common among the elderly; it is responsible for 60-80% of all dementia cases. AD is characterized by cognitive decline, behavioural and psychological symptoms, and reductions in functioning and independence. Because of its progressive neurodegenerative nature and unknown aetiology, the burden of AD becomes increasingly significant in an aging population. Estimates indicate that 35.6 million people worldwide suffered from AD in 2010. By 2030 and 2050, this figure is predicted to increase to 65.7 million and 115.4 million, respectively. Costs will also rise along with the increase in the number of people diagnosed with AD. In 2010, the worldwide costs associated with dementia were estimated to be $US604 billion. The objective of this study was to conduct a systematic review of current publications dealing with the pharmacoeconomic factors associated with AD medications and to describe the decision-analytic models used to evaluate long-term outcomes. A systematic literature search was performed to identify articles published between 1 January 2007 and 15 July 2010. The search was also based on a previous systematic review, which included literature up to 2007. Articles were included if they were complete and original economic evaluations of AD and if they were comparative in nature. A quality assessment of the included publications was conducted and relevant information was extracted into tables. Seven out of 2067 identified articles were included in this systematic review. Four articles evaluated treatment with donepezil, one with galantamine and two with memantine. The studies were conducted in America, Europe and Asia. Five different groups of medications were compared. The incremental cost-effectiveness ratios (ICERs) for the group of patients treated with donepezil versus no drug treatment ranged from a dominant value to 281, 416.13 euros per quality-adjusted life-year (QALY). Patients treated with donepezil versus placebo showed ICERs with a range from a dominant value (not specified) up to 20, 866.77 euros per QALY. Treatment with memantine in addition to donepezil versus treatment with donepezil alone showed an ICER range from a dominant value to 6818.33 euros per QALY. In comparison with the memantine treatment as an add-on therapy, the ICER of memantine monotherapy versus standard care (without cholinesterase inhibitors [CEIs]) ranged from a dominant value to 63, 087.20 euros per QALY. Finally, the economic evaluation of galantamine in comparison with usual care without any AD drugs showed ICERs ranging from 1894.70 euros to 6953 euros per QALY. The seven identified publications included in this review indicate that treatment with CEIs or memantine seems to be reasonable in terms of clinical effects and costs for patients with AD. Depending on different hypotheses, assumptions and variables (e.g. time horizon, discount rates, initial number of patients in different states, etc.) in the sensitivity analyses, treatment with these drugs seems to be primarily a cost-effective strategy or even a cost-saving strategy. Nevertheless, the results generally are associated with a degree of uncertainty. The comparability of the results from the different economic evaluations is limited because of the different assumptions made.

Extracting β-amyloid from Alzheimer's disease

The amyloid hypothesis of Alzheimer's disease (AD) posits that extracellular plaques comprised of the β-amyloid (Aβ) peptide are a root cause of neuronal loss in AD (1). To date, three therapeutic strategies targeting Aβ have been used: (i) inhibiting the production of Aβ, (ii) inhibiting the oligomerization of Aβ, and (iii) promoting the clearance and/or degradation of Aβ. None have led to a therapeutic or preventive medication for AD. As an alternative approach, natural compounds have demonstrated remarkable promise in diseases ranging from cancer to diabetes. In PNAS, Sehgal et al. (2) describe how an extract from the root of Withania somnifera (WS; also known as Ashwagandha or Indian ginseng) reverses AD pathology via the peripheral clearance of Aβ.

Nanotechnology for Alzheimer’s disease detection and treatment

In this paper, we present the role of nanotechnology in the development and improvement of techniques for early diagnosis and effective treatment of Alzheimer's disease (AD). Since AD pathology is almost irreversible and presentday medications for AD only lower its associated symptoms, application of diseasemodifying treatments could be successful only if AD early diagnosis is possible. The nanodiagnostic methods reported and compared in this paper include both of in vitro and in vivo nature. Of the in vitro approaches, the DNAnanoparticle conjugates (bioba rcode assay), nanoparticle surface plasmon resonance, scanning tunneling microscopy, and twophoton Rayleigh spectroscopy are presented here. Of the in vivo methods, µMRI and optical imaging techniques are discussed here. The nanotreatment methods for AD are numerous. They are categorized in this report under neuroprotective methods from toxicity of amyloid�β peptide (Aβ) oligomers , oxidative stress of free radicals and nanocarriers for targeted drug delivery. The important agents for neuroprotection include nanogels, fullerene, nanoceria, dendrimers, gold nanoparticles, and diamondoid derivatives. The major nanocarriers presented here include cholinesterase inhibitors nanocarriers, acetylcholine nanocarrier, metal chelator nanocarriers, (Iron chelators and copper chelators), curcuminoids nanocarrier, antioxidant nanocarriers, and gene nanocarriers. Considering that the AD is a multifactorial disease with several pathogenetic mechanisms and pathways, a multifunctional nanotechnology approach will be needed to target its main molecular culprits. These molecular targets must include, but not limited to, Aβ oligomers, reactive oxygen species (ROS), excessive metal ions, tau phosphorylating kinases and cell cycle proteins.