Alzheimer Disease: Winblad B

Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, Scheltens P, Tariska P, Winblad B, Anonymous00263. · Memory Disorders Research Group, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Denmark. · Eur J Neurol. · Pubmed #17222085 No free full text.

Abstract: The aim of this international guideline on dementia was to present a peer-reviewed evidence-based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists, and other specialist physicians responsible for the care of patients with dementia. It covers major aspects of diagnostic evaluation and treatment, with particular emphasis on the type of patient often referred to the specialist physician. The main focus is Alzheimer's disease, but many of the recommendations apply to dementia disorders in general. The task force working group considered and classified evidence from original research reports, meta-analysis, and systematic reviews, published before January 2006. The evidence was classified and consensus recommendations graded according to the EFNS guidance. Where there was a lack of evidence, but clear consensus, good practice points were provided. The recommendations for clinical diagnosis, blood tests, neuroimaging, electroencephalography (EEG), cerebrospinal fluid (CSF) analysis, genetic testing, tissue biopsy, disclosure of diagnosis, treatment of Alzheimer's disease, and counselling and support for caregivers were all revised when compared with the previous EFNS guideline. New recommendations were added for the treatment of vascular dementia, Parkinson's disease dementia, and dementia with Lewy bodies, for monitoring treatment, for treatment of behavioural and psychological symptoms in dementia, and for legal issues. The specialist physician plays an important role together with primary care physicians in the multidisciplinary dementia teams, which have been established throughout Europe. This guideline may contribute to the definition of the role of the specialist physician in providing dementia health care.

Palmer K, Jelic V, Winblad B. · Division of Geriatric Epidemiology and Medicine, Neurotec, Karolinska Institutet and Stockholm Gerontology Research Center, Stockholm, Sweden. · Acta Neurol Scand Suppl. · Pubmed #12603243 No free full text.

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Winblad B, Wimo A, Möbius HJ, Fox JM, Fratiglioni L. · No affiliation provided · Int J Geriatr Psychiatry. · Pubmed #10556861 No free full text.

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Winblad B. · Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge, Sweden. · Eur Neuropsychopharmacol. · Pubmed #10332933 No free full text.

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Winblad B, Machado JC. · Karolinska Institutet Alzheimer's Disease Research Center (KI-ADRC), Floor 5, S-14157, NOVUM, Huddinge, Sweden. · Expert Opin Drug Deliv. · Pubmed #19040398 No free full text.

Abstract: Cholinesterase inhibitors such as rivastigmine and donepezil exhibit a dose-response relationship, with higher doses of the drugs demonstrating greater efficacy. Transdermal patches provide smooth continuous drug delivery, with the potential to offer efficacious levels of drug exposure while avoiding the peaks and troughs associated with side effects. As a small, lipophilic and hydrophilic molecule, rivastigmine (C14H22N2O2) is chemically well-suited to transdermal delivery. The technology underlying the rivastigmine patch allows it to be discreetly small and thin. The target dose 9.5 mg/24 h rivastigmine patch has a diameter of just 3.5 cm and a surface area of 10 cm2. A large randomized controlled trial has demonstrated that the target dose 9.5 mg/24 h rivastigmine patch provided similar efficacy to the highest rivastigmine capsule doses, yet with three times fewer reports of nausea and vomiting. Thus, the rivastigmine patch enables quick and easy access to high dose efficacy. The skin tolerability profile is good, and the patch has demonstrated excellent adhesion. The apparent success of rivastigmine patch, in terms of clinical utility and patient acceptability, suggests that it may mark the next generation of dementia treatment.

Pei JJ, Sjögren M, Winblad B. · Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, KI-ADRC, Novum, Stockholm, Sweden. · Curr Opin Psychiatry. · Pubmed #18852562 No free full text.

Abstract: PURPOSE OF REVIEW: Great progress has been made in understanding the pathogenesis of neurofibrillary degeneration in Alzheimer's disease brains in the last two decades. In this review we summarize how neurons are degenerated in Alzheimer's disease brains and highlight the evidence of using kinases such as glycogen synthase kinase 3 and p70 S6 kinase and phosphatases such as protein phosphatase 2A as drug targets to prohibit the formation of neurofibrillary degeneration of Alzheimer's disease. RECENT FINDINGS: In general there are two types of neuronal degeneration in Alzheimer's disease brains: neurofibrillary formation and apoptosis. The microtubule-associated protein tau that stabilizes neuronal microtubules under normal physiological conditions is abnormally hyperphosphorylated in Alzheimer's disease brains, resulting in the generation of aberrant aggregates that are toxic to neurons. The processes of tau hyperphosphorylation and the formation of neurofibrillary tangles are caused by the imbalance of the activities of protein kinases and protein phosphatases in Alzheimer's disease brains. Recent findings from our and other groups have suggested glycogen synthase kinase 3 and p70 S6 kinase as main tau kinases and protein phosphatase 2A as the main tau phosphatase involved in the formation of these processes. Activities of these targets are implicated by Abeta peptide, the major component of another hallmark in Alzheimer's disease brains, senile plaques. SUMMARY: To prevent the clinical progression of neurodegeneration, a combination strategy is suggested to target both senile plaques with immunization and neurofibrillary tangles with drugs to prevent the synthesis and phosphorylation of tau.

Pei JJ, Björkdahl C, Zhang H, Zhou X, Winblad B. · Karolinska Institutet, KI-Alzheimer Disease Research Center, Novum, Huddinge, Sweden. · J Alzheimers Dis. · Pubmed #18688088 No free full text.

Abstract: The 70-kDa S6 kinase (p70S6K) is a Ser/Thr (S/T)-directed kinase that plays a crucial role in cell growth, cell differentiation, and cell cycle control. This article presented evidence that supports both toxic and protective roles of p70S6K activity towards tau in Alzheimer's disease (AD) brains. The p70S6K can phosphorylate tau at S262, S214, and T212 sites. Phosphorylation at these sites might release tau from microtubules, resulting in microtubule disruption. Evidence also suggests that p70S6K regulates the translation of tau mRNA by phosphorylating the 40S ribosomal protein S6. The extracellular amyloid-beta deposition in AD brains could be a causative factor that activates p70S6K. We hypothesized that amyloid-beta deposition activates p70S6K whose anti-apoptotic property subsequently keeps neurons from entering into the apoptotic process. This process provides the opportunity for the newly synthesized tau to be phosphorylated by p70S6K and by other tau kinases. This hyperphosphorylated tau then aggregates and is progressively deposited in neurons.

Winblad B, Fioravanti M, Dolezal T, Logina I, Milanov IG, Popescu DC, Solomon A. · Karolinska Institute - Alzheimer Disease Research Center, Stockholm, Sweden. · Clin Drug Investig. · Pubmed #18666801 No free full text.

Abstract: The ergot alkaloid derivative nicergoline became clinically available about 35 years ago in the 1970s. Nicergoline has a broad spectrum of action: (i) as an alpha(1)-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties. Acting on several basic pathophysiological mechanisms, nicergoline has therapeutic potential in a number of disorders. This article provides an overview of the published clinical evidence relating to the efficacy and safety of nicergoline (30 mg twice daily) in the treatment of dementia (including Alzheimer's disease and vascular dementia) and vascular and balance disorders. For dementia of different aetiologies, the therapeutic benefit of nicergoline has been established, with up to 89% of patients showing improvements in cognition and behaviour. After as little as 2 months of treatment, symptom improvement is apparent compared with placebo, and most patients are still improved or stable after 12 months. Concomitant neurophysiological changes in the brain indicate (after only 4-8 weeks' treatment) improved vigilance and information processing. In patients with balance disorders, mean improvements of 44-78% in symptom severity and quality of life have been observed with nicergoline. Although clinical experience with nicergoline in vascular disorders is limited to relatively short-term, small-scale studies, it has been successfully used in rehabilitation therapy of patients with chronic ischaemic stroke. Open-label evaluations suggest that nicergoline may also be valuable in glaucoma, depression and peripheral arterio-pathy. Adverse events of nicergoline, if any, are related to the central nervous system, the metabolic system and the overall body. Most are considered typical symptoms of ergot derivatives. Because of their generally mild and transient nature, treatment discontinuations occur relatively infrequently. The efficacy of nicergoline combined with a favourable safety and tolerability profile at commonly applied doses (60 mg/day) make this agent a valuable therapy in patients with mild to moderate dementia, vascular diseases and balance disorders.

Edvardsson D, Winblad B, Sandman PO. · Department of Nursing, Umea University, Sweden. · Lancet Neurol. · Pubmed #18339351 No free full text.

Abstract: When caring for people with severe Alzheimer's disease (AD), the concept of the person being central is increasingly advocated in clinical practice and academia as an approach to deliver high-quality care. The aim of person-centred care, which emanates from phenomological perspectives on AD, is to acknowledge the personhood of people with AD in all aspects of their care. It generally includes the recognition that the personality of the person with AD is increasingly concealed rather than lost; personalisation of the person's care and their environment; offering shared decision-making; interpretation of behaviour from the viewpoint of the person; and prioritising the relationship as much as the care tasks. However, questions remain about how to provide, measure, and explore clinical outcomes of person-centred care. In this Review, we summarise the current knowledge about person-centred care for people with severe AD and highlight the areas in need of further research.

Cummings J, Winblad B. · UCLA Alzheimer's Center, 10911 Weyburn Avenue, Suite 200, Los Angeles, CA 90095-7226, USA. · Expert Rev Neurother. · Pubmed #17997695 No free full text.

Abstract: Rivastigmine patch is the first transdermal treatment to be approved for Alzheimer's disease (AD) and Parkinson's disease dementia in the USA and for AD in Europe. It provides smooth, continuous drug delivery, and has the potential to maintain rivastigmine concentrations within an optimal therapeutic window while avoiding the peaks and troughs associated with oral drug delivery. The target dose, rivastigmine 9.5 mg/24 h patch (a 10 cm(2) patch), is given once daily and requires a simple one-step dose titration to the therapeutic dose. In a 24-week study in 1195 AD patients, the rivastigmine 9.5 mg/24 h patch provided similar efficacy to the highest dose range of capsules, with approximately three-times fewer reports of nausea and vomiting. Patients in the 9.5 mg/24 h patch and 12 mg/day capsule groups evidenced significant improvements versus placebo on both primary outcome measures: the Alzheimer's Disease Assessment Scale-Cognitive subscale; and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change; in addition to the following secondary outcome measures: Alzheimer's Disease Cooperative Study-Activities of Daily Living scale; Mini-Mental State Examination; and Trail Making Test Part A for assessment of attention, visual tracking and motor processing speed. Treatment differences on the Neuropsychiatric Inventory and Ten Point Clock-drawing Test did not reach statistical significance in this study. The patch may be the optimal way to treat dementia patients with rivastigmine.

Laudon H, Winblad B, Näslund J. · Karolinska Institutet, Alzheimer Disease Research Center, Huddinge, Sweden. · Physiol Behav. · Pubmed #17588625 No free full text.

Abstract: Alzheimer's disease is neuropathologically characterized by the presence of neurofibrillary tangles and amyloid plaques in the brain. Amyloid plaques are extracellular deposits primarily composed of the amyloid beta-peptide, which is derived from the amyloid beta-precursor protein (APP) by sequential cleavages at the beta-secretase and gamma-secretase sites. gamma-Secretase cleavage is performed by a high molecular weight protein complex containing presenilin (PS), nicastrin, Aph-1 and Pen-2. The gamma-secretase complex is an unusual transmembrane aspartyl protease that cleaves APP within the transmembrane domain. In addition to APP, a large number of other single membrane-spanning proteins have been shown to be cleaved within their transmembrane domains by the gamma-secretase complex in a process referred to as regulated intramembrane proteolysis. Here we review recent research leading to the identification and understanding of the gamma-secretase complex components with emphasis on PS, which harbors the catalytic site. In addition, we summarize our own work focused on identifying and studying domains in PS1 that are critical for mediating gamma-secretase activity. Biochemical understanding of the gamma-secretase complex is important from a basic biological and physiological point of view, and could help in the development of small molecules that modulate gamma-secretase processing in an APP-specific manner.

Fratiglioni L, Winblad B, von Strauss E. · Karolinska Institutet, Aging Research Center, Division of Geriatric Epidemiology, NVS, and Stockholm Gerontology Research Center, Gävlegatan 16, S-113 30 Stockholm, Sweden. · Physiol Behav. · Pubmed #17588621 No free full text.

Abstract: The aging of the population is a worldwide phenomenon, and studying age-related diseases has become a relevant issue from both a scientific and a public health perspective. This review summarises the major findings concerning prevention of Alzheimer's disease (AD) and other dementias from a population-based study, the Kungsholmen Project. The study addresses risk- and protective factors for AD and dementia from a lifetime perspective: at birth, during childhood, in adult life, and in old age. Although many aspects of the dementias are still unclear, some risk factors have been identified and interesting hypotheses have been suggested for other putative risk or protective factors. At the moment it is also possible to delineate some preventative strategies for dementia.

Codita A, Winblad B, Mohammed AH. · Karolinska Institutet, NVS, KI Alzheimer's Disease Research Centre, Novum, Stockholm, Sweden. · Curr Opin Psychiatry. · Pubmed #17012931 No free full text.

Abstract: PURPOSE OF REVIEW: An increasing number of genetically modified mouse models are designed and used in the field of Alzheimer disease research. This review aims to offer a general view of the existing transgenic mouse lines and to discuss their relevance and limitations. RECENT FINDINGS: Potential therapeutic targets have been identified in rodent models of Alzheimer disease. Although important steps towards obtaining a safe vaccine to prevent amyloid plaque formation have been made, further evaluations and the use of intermediate models are considered a necessity. SUMMARY: More than 18 million people worldwide are suffering from Alzheimer disease, the most common dementing disorder in humans. Transgenic lines have been created in order to understand the underlying mechanisms of Alzheimer disease and to find a cure. None of the available models completely recapitulates the characteristics of human pathology, but they provide valuable information on different pathogenic pathways involved. New therapeutic approaches and improvement of current strategies can be obtained from the use of Alzheimer animal models.

Jelic V, Kivipelto M, Winblad B. · Karolinska Institutet, Neurotec Department, Division of Geriatric Medicine, Karolinska University Hospital-Huddinge, Stockholm, Sweden. · J Neurol Neurosurg Psychiatry. · Pubmed #16306154 links to  free full text

Abstract: Mild cognitive impairment (MCI) is an operational definition for a cognitive decline in individuals with a greater risk of developing dementia. The amnestic subtype of MCI is of particular interest because these individuals most likely progress to Alzheimer's disease (AD). Currently hypothesised therapeutic approaches in MCI are mainly based on AD treatment strategies. Long term secondary prevention randomised clinical trials have been completed in amnestic MCI populations, encompassing agents with various mechanisms of action: acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine), antioxidants (vitamin E), anti-inflammatories (rofecoxib), and nootropics (piracetam). The design of clinical trials in MCI is influenced by study objectives and definition of primary end points: time to clinical diagnosis of dementia, and AD in particular, or symptom progression. As none of the drugs previously shown to have clinical efficacy in AD trials or benefit in everyday practice have met the primary objectives of the respective trials, design of future clinical trials in MCI should be further developed particularly as regards the selection of more homogeneous samples at entry, optimal treatment duration, and multidimensional and reliable outcomes.

Qiu C, Winblad B, Fratiglioni L. · Aging Research Centre, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institute and Stockholm Gerontology Research Centre, Stockholm, Sweden. · Lancet Neurol. · Pubmed #16033691 No free full text.

Abstract: The relation of blood pressure with cognitive function and dementia has, in recent years, received much attention from epidemiological research. Some cross-sectional studies have shown an inverse association between blood pressure and the prevalence of dementia and Alzheimer's disease, whereas longitudinal studies yield mixed results that largely depend on the age at which blood pressure is measured and the time interval between blood pressure and outcome assessments. Some studies suggest that midlife high blood pressure is a risk factor for late-life cognitive impairment and dementia, and that low diastolic pressure and very high systolic pressure in older adults may be associated with subsequent development of dementia and Alzheimer's disease. Observational studies and randomised clinical trials provide limited evidence for a protective effect of antihypertensive therapy against dementia and stroke-related cognitive decline. Atherosclerosis resulting from long-standing hypertension, and cerebral hypoperfusion secondary to severe atherosclerosis and to low blood pressure may be major biological pathways linking both high blood pressure in midlife and low blood pressure in late-life to cognitive decline and dementia.

Ankarcrona M, Winblad B. · Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, Huddinge, Sweden. · Int J Geriatr Psychiatry. · Pubmed #15660410 No free full text.

Abstract: Alzheimer's disease (AD) affects millions of people worldwide and the number of AD cases will increase with increased life expectancy. Today there is no cure for this devastating and always lethal disease and therefore it is of great interest for patients, relatives and societies to find new drugs that can hinder the disease process. During the progression of AD a substantial amount of neurons degenerate in the brain. The mechanisms of cell death involved in AD have not been fully elucidated. However, there are several reports showing that neurons die partly by apoptosis in the AD brain. Drugs blocking apoptosis could therefore be potentially useful for early prevention of neuronal cell death. Biomarkers for apoptosis should be important tools in the evaluation of drug effects and in the diagnostics of AD. Here we review the current knowledge in the field and discuss potential biomarkers for apoptosis in AD.

Winblad B, Jelic V. · Karolinska Institutet, Alzheimer's Disease Research Center, Neurotec Department, Division of Geriatric Medicine, Karolinska University Hospital-Huddinge, Stockholm, Sweden. · Alzheimer Dis Assoc Disord. · Pubmed #15249842 No free full text.

Abstract: During the past 20 years, research on Alzheimer disease (AD) and other dementias has increased our understanding of these disorders and has opened doors to new methods of treatment. Acetylcholinesterase inhibitors (AChEIs) have been successful in reducing symptoms in patients with mild-to-moderate AD and led to the US Food and Drug Administration's approval of four AChEIs for the treatment of AD. Although these agents are approved for only mild-to-moderate AD, and the available data for most of them are from trials of only 6 months' duration, long-term studies suggest that the benefits of AChEI treatment can endure for up to 4 years. A common pattern of response to treatment is initial improvement in cognition, followed by maintenance of cognitive gains above baseline for up to 1 year. Generally there is a decline in cognition to below baseline levels after approximately 1 year of treatment, but the level of cognition remains above that predicted for those not receiving pharmacologic treatment. Furthermore, long-term studies suggest that early diagnosis and treatment with AChEIs yield better long-term outcomes. Patients who received continuous pharmacologic treatment from the outset generally had better long-term outcomes than those who received placebo in the double-blind phase of these trials.

Fratiglioni L, Paillard-Borg S, Winblad B. · Aging Research Center, Division of Geriatric Epidemiology and Medicine, Neurotec Department, Karolinska Institute and Stockholm Gerontology Research Center, Stockholm, Sweden. · Lancet Neurol. · Pubmed #15157849 No free full text.

Abstract: The recent availability of longitudinal data on the possible association of different lifestyles with dementia and Alzheimer's disease (AD) allow some preliminary conclusions on this topic. This review systematically analyses the published longitudinal studies exploring the effect of social network, physical leisure, and non-physical activity on cognition and dementia and then summarises the current evidence taking into account the limitations of the studies and the biological plausibility. For all three lifestyle components (social, mental, and physical), a beneficial effect on cognition and a protective effect against dementia are suggested. The three components seem to have common pathways, rather than specific mechanisms, which might converge within three major aetiological hypotheses for dementia and AD: the cognitive reserve hypothesis, the vascular hypothesis, and the stress hypothesis. Taking into account the accumulated evidence and the biological plausibility of these hypotheses, we conclude that an active and socially integrated lifestyle in late life protects against dementia and AD. Further research is necessary to better define the mechanisms of these associations and better delineate preventive and therapeutic strategies.

Religa D, Winblad B. · Neurotec, Section of Experimental Geriatrics, Karolinska Institutet, Stockholm, Sweden. · Acta Neurobiol Exp (Wars). · Pubmed #15053264 links to  free full text

Abstract: BACKGROUND AND OBJECTIVE: Alzheimer's disease (AD)--the main cause of dementia--is characterized by the presence of neuritic plaques containing the amyloid-beta peptide (A beta) and an intraneuronal accumulation of tubule-associated protein called tau. The current and future therapeutic strategies for AD will be discussed. Currently available treatment used in AD is based on acetylcholinesterase inhibitors, since in the course of AD there is a substantial loss in cholinergic neurons. Another registered drug used in more severe AD is NMDA antagonist--memantine. Available strategies for AD include vitamin supplementation for reducing homocysteine levels, statins and non-steroidal anti-inflammatory drugs. The big hope of the last few years--vitamin E and estrogen supplementation have not been proved efficient, but more studies are needed. There are several strategies aimed at acting directly on A beta or amyloid precursor protein (APP) processing: vaccination with A beta peptide, A beta passive immunization, beta and gamma secretases inhibitors. Nerve growth factors and neurotrophines could also be targeted by new therapies. CONCLUSIONS: A better understanding of the role of APP processing and folate and homocysteine in neuronal homeostasis throughout life consist revealing novel and relatively inexpensive approaches for preventing and treating AD.

Algotsson A, Winblad B. · Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Division of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden. · Dement Geriatr Cogn Disord. · Pubmed #14739530 No free full text.

Abstract: In epidemiological, cross-sectional studies, treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) prevented to a large extent the development of Alzheimer's disease (AD), but the results of randomized, placebo-controlled studies, focused on statin therapy in patients with ischemic heart disease (IHD), are at variance. Nonetheless, data from epidemiological, longitudinal studies in humans as well as studies on transgenic mouse models and cultured neuronal cell lines indicate that cholesterol may contribute to the pathogenesis of AD. Statins have proven therapeutic and preventive effects in IHD and other vascular diseases in man. They generally are well tolerated, but some adverse effects, probably due to antiproliferative and proapoptotic properties of the statins, are matters of concern. AD patients may be extrasusceptible to adverse effects of statins due to preexisting aberrations in signal transduction and energy metabolism in the neurons and a perturbed cholesterol metabolism in the brain. This problem might be addressed in randomized, double-blind studies with statins in AD. The statins differ from each other in several aspects, and they are not considered to be therapeutically interchangeable. It could be fruitful to use both a placebo and two different types of statins, i.e. an essentially hydrophilic statin and a lipophilic statin, in a double-blinded fashion, and to compare the effects on the cognitive decline in AD.

Winblad B, Blum KI. · Karolinska Institutet, Department of Neurotechnology, Division of Geriatrics, Huddinge University Hospital, SE-141 86 Stockholm, Sweden. · Neuron. · Pubmed #12765602 No free full text.

This publication has no abstract.

Winblad B, Möbius HJ, Stöffler A. · Karolinska Institute and Neurotec, Stockholm, Sweden. · J Neural Transm Suppl. · Pubmed #12456065 No free full text.

Abstract: Several years after the introduction of cholinergic drugs in Alzheimer's disease therapy, other approaches for symptomatic and also disease-modifying pharmacotherapy are progressing in their development. Among these, the NMDA antagonist memantine represents the most advanced and promising agent, gifted with many years of clinical experience in Germany. This paper provides an overview of both, the novel pharmacological background and recent clinical evidence in dementia. Memantine was recently recommended for central European approval.

Crisby M, Carlson LA, Winblad B. · The Alzheimer Disease Research Center, Karolinska Institute, Neurotec Division of Geriatric Medicine, Huddinge University Hospital, Stockholm, Sweden. · Alzheimer Dis Assoc Disord. · Pubmed #12218642 No free full text.

Abstract: Vascular risk factors such as hypertension and hypercholesterolemia during midlife increase the risk for Alzheimer's disease (AD). Treatment of hypercholesterolemia and other vascular risk factors may have great implications in the prevention of AD. Recent findings illustrate that the sterol metabolism in the brain is an active process, well controlled and regulated by 24-hydroxylase, an enzyme that is uniquely expressed in the brain. The use of statins in ischemic heart disease (IHD) has proven to be a phenomenal advance in pharmacological disease prevention and treatment. A growing body of evidence, suggest that statins exhibit additional benefits that are independent of their cholesterol-lowering actions. Statin treatment has also considerable effect in prevention of ischemic stroke. In animal models of ischemic stroke, statins have proven to reduce infarct size through up-regulation of endothelial nitric oxide synthases. Data from recent observational studies have revealed a potential role for statins in prevention of AD. The following review comments the processes leading to dementia including the involvement of cholesterol regulation, cerebral circulation and inflammation in development of dementia. The mechanisms by which statins may be beneficial in controlling these processes is discussed.

Carlson LA, Winblad B. · Royal College of Physicians, Konung Gustaf V:s forskningsinstitut, Karolinska institutet, Karolinska sjukhuset, Stockholm. · Lakartidningen. · Pubmed #11586810 No free full text.

This publication has no abstract.

Winblad B, Brodaty H, Gauthier S, Morris JC, Orgogozo JM, Rockwood K, Schneider L, Takeda M, Tariot P, Wilkinson D. · Karolinska Institutet, Alzheimer Research Center, Huddinge University Hospital, Stockholm, Sweden. · Int J Geriatr Psychiatry. · Pubmed #11466744 No free full text.

Abstract: The traditional aim of Alzheimer's disease treatment in clinical trials has been to improve cognitive abilities. It has become increasingly clear, however, that other aspects are important in assessing treatment responses. A group of 10 physicians recently gathered to review the current criteria for assessing treatment success in Alzheimer's disease. While cognition has been previously viewed as the primary measure of efficacy, areas such as functional abilities, behaviour, caregiver burden, quality of life and resource utilization all need to be comprehensively assessed to fully evaluate treatment effects in patients with Alzheimer's disease, as well as their impacts on caregivers and society. Postponing or slowing decline in any of these areas may represent an important benefit and should be considered as an outcome measure in clinical trials, clinical practice and decision-making about healthcare budgets. Accepted instruments are available for assessing outcomes in each aspect of Alzheimer's disease, but they need to be selected carefully to provide valid, meaningful data. Some of the most frequently used outcome measures in Alzheimer's disease are reviewed. Using expanded criteria for treatment success and clinically relevant outcome measures, data from currently available studies show that cholinesterase inhibitors produce clinically meaningful long-term benefits in multiple domains in patients with Alzheimer's disease.