Alzheimer Disease: US Federal Service

Quinn JF, Crane S, Harris C, Wadsworth TL. · Oregon Health and Science University, Portland VA Medical Center, Department of Neurology, Portland, OR 97239, USA. · Expert Rev Neurother. · Pubmed #19402774 No free full text.

Abstract: A considerable amount of literature has accrued examining the role of copper in the pathogenesis of Alzheimer's disease. Remarkably, there is in vitro and animal data to support both copper toxicity and copper deficiency as relevant mechanisms in Alzheimer's disease. These data have prompted preliminary clinical trials of both copper complexing therapy and copper supplementation therapy, which have yielded mixed results. The preclinical and clinical studies are discussed here in an effort to determine how to move forward with rational clinical trials focused on copper modulation.

Petanceska S, Ryan L, Silverberg N, Buckholtz N. · Division of Neuroscience, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. · Alzheimers Dement. · Pubmed #19328442 No free full text.

This publication has no abstract.

Craft S. · Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, 98108, USA. · Arch Neurol. · Pubmed #19273747 No free full text.

Abstract: In recent years a rapidly increasing number of studies has focused on the relationship between dementia and metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. Etiological heterogeneity and comorbidity pose challenges for determining relationships among metabolic disorders. The independent and interactive effects of brain vascular injury and classic pathological agents such as beta-amyloid have also proved difficult to distinguish in human patients, blurring the lines between Alzheimer disease and vascular dementia. This review highlights recent work aimed at identifying convergent mechanisms such as insulin resistance that may underlie comorbid metabolic disorders and thereby increase dementia risk. Identification of such convergent factors will not only provide important insight into the causes and interdependencies of late-life dementias but will also inspire novel strategies for treating and preventing these disorders.

Henry RG, Smith BJ. · Department of Dental Services (160), Veterans Affairs Medical Center, Cooper Dr. Division, Lexington, KY 40502, USA. · Dent Clin North Am. · Pubmed #19269397 No free full text.

Abstract: Neurologic diseases represent some of the most common disabling and costly conditions in older age. Alzheimer disease and cerebrovascular accidents (strokes) are two of the most common neurologic conditions, and represent the leading causes of nursing home placement. Dental professionals will be caring for older patients who have age-associated neurologic diseases, including Alzheimer disease and stroke because of the increased longevity of the United States population coupled with improved survivorship of these conditions as a result of advanced medical diagnosis and treatment. Understanding the clinical manifestations of these two common, but distinctly different, neurologic conditions will enable dental professionals to provide safe and rational dental care.

Manolio TA. · National Human Genome Research Institute, Building 31, Room 4B-09, 31 Center Drive, MSC 2154, Bethesda, MD 20892-2154, USA. · Pharmacogenomics. · Pubmed #19207024 No free full text.

Abstract: In the past 3 years, genome-wide association (GWA) studies have revolutionized the discovery of genetic variants associated with complex diseases. These studies present unique challenges in their conduct; particularly in the need for meticulous quality control of genotyping and for sample sizes large enough to withstand the severe penalty for multiple comparisons necessitated by testing hundreds of thousands of SNPs. They also present unique opportunities in the unprecedented detail with which they characterize an individual's genome and the potential for relating that information to any trait consistent with that person's informed consent. Such data exceed the abilities of any single group of investigators to mine them fully and by NIH policy are distributed to qualified investigators agreeing to specified terms of use. This report describes collaborative programs of the National Human Genome Research Institute's Office of Population Genomics for facilitating collection, analysis, interpretation, and dissemination of these data so that their research value can be maximized.

Shie FS, Nivison M, Hsu PC, Montine TJ. · Division of Mental Health and Substance Abuse Research, National Health Research Institutes, No.35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, R.O.C. · Curr Med Chem. · Pubmed #19199928 No free full text.

Abstract: Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Although the etiology of AD remains unclear, microglia-mediated neuroinflammation is believed to play an important role in its pathogenesis. Microglial activation occurs in AD and is characterized by apparent phagocytic activity and by increased production and secretion of several cytokines, chemokines, reactive oxygen and nitrogen species, prostaglandin (PG)E2, and neurotrophic factors. Microglial activation can be neuroprotective through the release of neurotrophic factors and by phagocytosing Abeta, a critical neurotoxic component in AD brain. Concurrently, microglial activation causes elevated inflammatory responses that lead to paracrine damage to neurons. Therefore, a well-controlled microglial activation that diminishes microglial-mediated oxidative damage while promoting neuronal protection may be the key for AD therapy. Peroxisome proliferator-activated receptor gamma (PPARgamma) has recently gained increasing attention in AD due to its function as a molecular target for non-steroidal anti-inflammatory drugs (NSAIDs). In this review, we will discuss the role of PPARgamma in microglial innate immunity in AD and how pharmacological manipulation of microglial activation using PPARgamma ligands might facilitate the treatment of AD.

Becker RE, Unni LK, Greig NH. · Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. · Curr Alzheimer Res. · Pubmed #19199879 No free full text.

Abstract: Commercial priorities have been identified as negative factors in drug development. We trace the problem to inattention to sound clinical pharmacology practices. When properly applied, clinical pharmacology and associated drug development sciences can, hand in hand, facilitate success in commercial drug development.

Banks WA. · GRECC, Veterans Affairs Medical Center-St. Louis, and Saint Louis University School of Medicine, Division of Geriatrics, Department of Internal Medicine, 915 N. Grand Blvd, St. Louis, MO 63106, USA. · BMC Neurosci. · Pubmed #19090999 links to  free full text

Abstract: Development of therapeutics for the central nervous system is one of the most challenging areas in drug development. This is primarily because, in addition to all of the other complications one faces in developing new drugs targeting peripheral sites, one must also negotiate the blood-brain barrier (BBB). There are dozens of strategies to overcome the obstacle of the BBB, but many of these are bound to fail, barring extreme serendipity, because they are based on an inaccurate or incomplete picture of the BBB. This article therefore starts with a brief review of the BBB as it pertains to drug development. It then examines some examples of the delivery of drugs to the central nervous system that are relevant to Alzheimer's disease, placing emphasis on peptides, antibodies, and antisense oligonucleotides.

Mattson MP. · Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA. · Ann N Y Acad Sci. · Pubmed #19076369 links to  free full text

Abstract: Glutamate's role as a neurotransmitter at synapses has been known for 40 years, but glutamate has since been shown to regulate neurogenesis, neurite outgrowth, synaptogenesis, and neuron survival in the developing and adult mammalian nervous system. Cell-surface glutamate receptors are coupled to Ca(2+) influx and release from endoplasmic reticulum stores, which causes rapid (kinase- and protease-mediated) and delayed (transcription-dependent) responses that change the structure and function of neurons. Neurotrophic factors and glutamate interact to regulate developmental and adult neuroplasticity. For example, glutamate stimulates the production of brain-derived neurotrophic factor (BDNF), which, in turn, modifies neuronal glutamate sensitivity, Ca(2+) homeostasis, and plasticity. Neurotrophic factors may modify glutamate signaling directly, by changing the expression of glutamate receptor subunits and Ca(2+)-regulating proteins, and also indirectly by inducing the production of antioxidant enzymes, energy-regulating proteins, and antiapoptotic Bcl-2 family members. Excessive activation of glutamate receptors, under conditions of oxidative and metabolic stress, may contribute to neuronal dysfunction and degeneration in diseases ranging from stroke and Alzheimer's disease to psychiatric disorders. By enhancing neurotrophic factor signaling, environmental factors such as exercise and dietary energy restriction, and chemicals such as antidepressants may optimize glutamatergic signaling and protect against neurological disorders.

Mattson MP, Ashery U. · Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA. · Trends Biochem Sci. · Pubmed #19008105 links to  free full text

Abstract: In Alzheimer's disease (AD), neurons suffer dysfunction and death associated with aberrant tau phosphorylation and subsequent neurofibrillary tangles. A new study reveals a surprising neuroprotective role for a truncated p73 isoform (DeltaNp73). Aged mice with reduced DeltaNp73 levels exhibit tau pathology and cognitive deficits, and DeltaNp73 reduction in mice with amyloid pathology causes extensive tangle formation and neuron death. These findings provide a novel animal model of AD and a potential therapeutic role for DeltaNp73 inducers.

Rapoport SI. · Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Building 9, Room 1S128, 9 Memorial Drive, Bethesda, MD 20892, USA. · Prostaglandins Leukot Essent Fatty Acids. · Pubmed #18973997 No free full text.

Abstract: Metabolic cascades involving arachidonic acid (AA) and docosahexaenoic acid (DHA) within brain can be independently targeted by drugs, diet and pathological conditions. Thus, AA turnover and brain expression of AA-selective cytosolic phospholipase A(2) (cPLA(2)), but not DHA turnover or expression of DHA-selective Ca(2+)-independent iPLA(2), are reduced in rats given agents effective against bipolar disorder mania, whereas experimental excitotoxicity and neuroinflammation selectively increase brain AA metabolism. Furthermore, the brain AA and DHA cascades are altered reciprocally by dietary n-3 polyunsaturated fatty acid (PUFA) deprivation in rats. DHA loss from brain is slowed and iPLA(2) expression is decreased, whereas cPLA(2) and COX-2 are upregulated, as are brain concentrations of AA and its elongation product, docosapentaenoic acid (DPA). Positron emission tomography (PET) has shown that the normal human brain consumes 17.8 and 4.6 mg/day, respectively, of AA and DHA, and that brain AA consumption is increased in Alzheimer disease patients. In the future, PET could help to determine how human brain AA or DHA consumption is influenced by diet, aging or disease.

Becker RE, Greig NH, Giacobini E. · Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. · J Alzheimers Dis. · Pubmed #18953116 No free full text.

Abstract: Alzheimer's disease (AD) drug developments and clinical trials (CT) remain vulnerable to problems that undermine research validity. Investigations of CT methods reveal how numerous factors decrease active drug-placebo group differences and increase variance, thereby reducing power to reach statistical significance for outcome measure differences in AD CTs. Such factors include, amongst many, inaccuracy, imprecision, bias, failures to follow or lack of operational protocols for applying CT methods, inter-site variance, and lack of homogeneous sampling using disorder criteria. After a review of the literature and survey of a sample of AD and Mild Cognitive Impairment (MCI) CTs, the authors question whether problems of human error preclude AD researchers from continuing their dependence on rated outcome measures for CTs. The authors propose that the realities of AD, especially a probable irreversible progression of neuropathology prior to onset of clinical symptoms or signs capable of differentiating persons at risk for AD from normal aged, require AD investigators and clinicians to privilege biomarkers and encourage their development as surrogate targets for preventive AD treatment developments, testing, and use in clinical practice.

Adibhatla RM, Hatcher JF. · Department of Neurological Surgery, Cardiovascular Research Center, Neuroscience Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI., William S. Middleton Veterans Affairs Hospital, Madison, WI 53792, USA. · Subcell Biochem. · Pubmed #18751914 links to  free full text

Abstract: Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice. Eicosapentaenoic acid supplementation provided improvement in schizophrenia patients, while the combination of (eicosapentaenoic acid + docosahexaenoic acid) provided benefit in bipolar disorders. The ketogenic diet where >90% of calories are derived from fat is an effective treatment for epilepsy. Understanding cytokine-induced changes in lipid metabolism will promote novel concepts and steer towards bench-to-bedside transition for therapies.

Becker RE, Greig NH. · Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. · Curr Alzheimer Res. · Pubmed #18690832 links to  free full text

Abstract: Recently, a number of Alzheimer's disease (AD) multi-center clinical trials (CT) have failed to provide statistically significant evidence of drug efficacy. To test for possible design or execution flaws we analyzed in detail CTs for two failed drugs that were strongly supported by preclinical evidence and by proven CT AD efficacy for other drugs in their class. Studies of the failed commercial trials suggest that methodological flaws may contribute to the failures and that these flaws lurk within current drug development practices ready to impact other AD drug development [1]. To identify and counter risks we considered the relevance to AD drug development of the following factors: (1) effective dosing of the drug product, (2) reliable evaluations of research subjects, (3) effective implementation of quality controls over data at research sites, (4) resources for practitioners to effectively use CT results in patient care, (5) effective disease modeling, (6) effective research designs. New drugs currently under development for AD address a variety of specific mechanistic targets. Mechanistic targets provide AD drug development opportunities to escape from many of the factors that currently undermine AD clinical pharmacology, especially the problems of inaccuracy and imprecision associated with using rated outcomes. In this paper we conclude that many of the current problems encountered in AD drug development can be avoided by changing practices. Current problems with human errors in clinical trials make it difficult to differentiate drugs that fail to evidence efficacy from apparent failures due to Type II errors. This uncertainty and the lack of publication of negative data impede researchers' abilities to improve methodologies in clinical pharmacology and to develop a sound body of knowledge about drug actions. We consider the identification of molecular targets as offering further opportunities for overcoming current failures in drug development.

Hodes RJ, Buckholtz N, Cahan V, Morrison-Bogorad M. · National Institute on Aging, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA. · Alzheimers Dement. · Pubmed #18631998 No free full text.

Abstract: The public Alzheimer's disease (AD) research enterprise began in earnest in the mid-1970s with the creation by Congress of the National Institute on Aging at the National Institutes of Health. Today, AD research is a maturing field of study, with federal effort seeking to encourage the creativity and insights of individual investigators, and targeting special areas for emphasis. It is inspired by the legacy of our friend and colleague Leon Thal, whose innovative and collaborative approach to scientific research serves as a guidepost as we move toward the discovery of new and effective ways to prevent AD or slow its progression. This article describes the progress to date and potentially promising areas of study from the vantage point of the National Institute on Aging.

Salinthone S, Yadav V, Bourdette DN, Carr DW. · Portland Veterans Affairs Medical Center, VAMC RD-8, 3710 Portland, OR 97239, USA. · Endocr Metab Immune Disord Drug Targets. · Pubmed #18537699 No free full text.

Abstract: The naturally occurring antioxidant lipoic acid (LA) was first described as an essential cofactor for the conversion of pyruvate to Acetyl-CoA, a critical step in respiration. LA is now recognized as a compound that has many biological functions. Along with its reduced form dihydrolipoic acid (DHLA), LA reduces and recycles cellular antioxidants such as glutathione, and chelates zinc, copper and other transition metal ions in addition to heavy metals. LA can also act as a scavenger of reactive oxygen and nitrogen species. By acting as an insulin mimetic agent, LA stimulates glucose uptake in many different cell types and can also modulate insulin signaling. The p38 and ERK MAP kinase pathways, AKT and NFkappaB are all regulated by LA. In addition, LA activates the prostaglandin EP2 and EP4 receptors to stimulate the production of the small molecule cyclic adenosine 5' monophosphate (cAMP). These diverse actions suggest that LA may be therapeutically effective in treating oxidative stress associated diseases. This review discusses the known biochemical properties of LA, its antioxidant properties, its ability to modulate signal transduction pathways, and the recent progress made in the utilization of LA as a therapeutic alternative for multiple sclerosis, Alzheimer's disease and diabetic neuropathy.

Crawley JN. · Laboratory of Behavioral Neuroscience, National Institute of Mental Health, Porter Neuroscience Research, Center Building 35, Room 1C-903, Mail Code 3730, Bethesda, Maryland 20892-3730, USA. · Cell Mol Life Sci. · Pubmed #18500642 links to  free full text

Abstract: The neuropeptide galanin and its receptors are localized in brain pathways mediating learning and memory. Central microinjection of galanin impairs performance of a variety of cognitive tasks in rats. Transgenic mice overexpressing galanin display deficits in some learning and memory tests. The inhibitory role of galanin in cognitive processes, taken together with the overexpression of galanin in Alzheimer's disease, suggests that galanin antagonists may offer a novel therapeutic approach to treat memory loss in Alzheimer's patients.

Ries ML, Carlsson CM, Rowley HA, Sager MA, Gleason CE, Asthana S, Johnson SC. · William S. Middleton Memorial Veterans Hospital Geriatric Research Education and Clinical Center, Madison, Wisconsin 53705, USA. · J Am Geriatr Soc. · Pubmed #18410325 links to  free full text

Abstract: Given the predicted increase in prevalence of Alzheimer's disease (AD) in the coming decades, early detection and intervention in persons with the predementia condition known as mild cognitive impairment (MCI) is of paramount importance. Recent years have seen remarkable advances in the application of neuroimaging and other biomarkers to the study of MCI. This article reviews the most recent developments in the use of magnetic resonance imaging (MRI) to characterize brain changes and to prognosticate clinical outcomes of patients with MCI. The review begins with description of methods and findings in structural MRI research, delineating findings regarding both gross atrophy and microstructural brain changes in MCI. Second, we describe the most recent findings regarding brain function in MCI, enumerating findings from functional MRI and brain perfusion studies. Third, we will make recommendations regarding the current clinical use of MRI in identification of MCI. As a conclusion, we will look to the future of neuroimaging as a tool in early AD detection.

Antai-Otong D. · Fort Worth Outpatient Clinic, Department of Veterans Affairs in Fort Worth, TX, USA. <> · Perspect Psychiatr Care. · Pubmed #18366366 No free full text.

This publication has no abstract.

Downey D. · Cleveland VA Medical Center, Cleveland, OH, USA. · J Neurosci Nurs. · Pubmed #18330411 No free full text.

Abstract: Although the diagnosis of AD can be devastating, treatment options exist that can slow the disease's progression and allow patients to continue performing ADLs, thereby improving the quality of life for both patient and caregiver. Research is ongoing, and it is estimated by the Alzheimer's Association that finding a treatment that could delay onset by only 5 years could reduce the number of individuals with AD by nearly 50% over the next 50 years (Alzheimer's Association, 2007). Although pharmacotherapy is not yet a cure, it does remain an important part of a total approach to caring for patients and families affected by AD.

Miller LJ. · Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas 77030, USA. · Consult Pharm. · Pubmed #18198970 No free full text.

Abstract: OBJECTIVE: To review the literature for double-blind, placebo-controlled trials that examined the efficacy of cognitive enhancers in the psychopathology of Alzheimer's disease. DATA SOURCES: Literature searches were conducted using MEDLINE and EMBASE databases and clinicaltrials.gov. STUDY SELECTION: Overall, 55 articles were reviewed for inclusion. Several open-label studies and case reports were found on this topic, but only those involving both tacrine and use of the Neuropsychiatric Inventory were included. Regarding other drugs, only double-blind, placebo-controlled trials were selected for inclusion. DATA SYNTHESIS: Limited data suggest that the anticholinesterase inhibitors and memantine offer an alternative or adjunct to the antipsychotics for the treatment of moderate-to-severe behaviors. The author reviewed the literature for pharmacological management of behavioral and psychological symptoms of dementia (BPSD) using these cognitive enhancers. CONCLUSION: The majority of patients with Alzheimer's disease will experience behavioral disturbances during the course of their disease. Atypical antipsychotics are used routinely in these situations to treat the psychotic features and agitation. However, atypicals now carry a "black box" warning issued by the Food and Drug Administration on the basis of evidence that their use in geriatric patients with dementia-related psychosis may put patients at increased risk of mortality as a result of cardiovascular or infectious events. An alternative to the atypicals may be the acetylcholinesterase inhibitors and memantine, which have been shown to stabilize cognitive as well as behavioral issues in patients, utilizing the "gold standard" for behavior, the Neuropsychiatric Inventory. Efficacy varies among agents, with the greatest positive effects seen with donepezil, which also has the greatest number of studies. Drug benefits were harder to demonstrate for mild-to-moderate BPSD compared with moderate-to-severe symptoms.

Shie FS, Woltjer RL. · Division of Mental Health and Substance Abuse, National Health Research Institutes, No.35 Keyan Road, Zhunan Town, Miaoli County 350, ROC, Taiwan. · Curr Med Chem. · Pubmed #18045132 No free full text.

Abstract: Alzheimer's disease (AD) is the leading cause of dementia. Although the etiology of AD remains controversial, the amyloid hypothesis suggests that beta-amyloid (Abeta) peptides may contribute to brain dysfunction, and microglial activation has become increasingly regarded as a potential contributor to disease pathogenesis. Microglial activation is characterized by morphological changes and by production of various effectors, and activated neuroinflammation concurrent with increased oxidative stress may contribute to damage to neurons. However, recently there has been a recognition that microglia may also play a neuroprotective role through their release of neurotrophic factors and through phagocytosis of Abeta. Thus, there is growing consensus that a favorable combination of diminished microglia-mediated neuroinflammation and enhanced Abeta clearance may be critical in AD therapy. In this review, we will discuss the role of microglial activation in AD and how pharmacologic manipulation of microglia might bear upon the treatment of AD.

Zhu CW, Sano M. · Geriatric Research, Education, and Clinical Center (GRECC) and Program of Research on Serious Physical and Mental Illness,Targeted Research Enhancement Program (TREP), Bronx VA Medical Center, Bronx, NY 10468. USA. · Clin Interv Aging. · Pubmed #18044111 links to  free full text

Abstract: Alzheimer's disease is a devastating chronic disease that significantly increases healthcare costs and affects the quality of life (QoL) of the afflicted patients and their caregivers. Population aging and other demographic changes may further increase the already staggering costs of this devastating disease. While few pharmacoeconomic studies have used a prospective health economics design to assess resource utilization, most studies showed beneficial treatment effects and suggested potential savings in healthcare costs and reductions in caregiver burden. Various degrees of cost savings have been reported depending on the type of economic model, treatment evaluated, and region used in the studies. Direct comparisons of the results are difficult because different methods have been used in these evaluations. The preference of patients and families for home care for as long as possible suggests that promoting noninstitutional care for these patients should become a priority. Continued home care for patients under pharmacological treatment may reduce caregiver burden, healthcare costs, and ultimately improve patients' and caregivers' QoL.

Martin JL, Ancoli-Israel S. · Veteran's Affairs Greater Los Angeles Healthcare System, Geriatric Research, Education and Clinical Center, 16111 Plummer Street, North Hills, CA 91343, USA. · Clin Geriatr Med. · Pubmed #18035230 links to  free full text

Abstract: Nighttime sleep disruption is characteristic of long-term care residents, is typically accompanied by daytime sleepiness, and may be caused by a multitude of factors. Causal factors include medical and psychiatric illness, medications, circadian rhythm abnormalities, sleep disordered breathing and other primary sleep disorders, environmental factors, and lifestyle habits. There is some suggestion that these factors are amenable to treatment; however, further research on the implementation of treatments within the long-term care setting is needed. Additional work is also needed to understand the administrative and policy factors that might lead to systemic changes in how sleep is viewed and sleep problems are addressed in long-term care settings.

Wright SL, Persad C. · Department of Psychiatry, University of Michigan Medical Center, Veterans Affairs Medical Center, GRECC, Ann Arbor, MI 48105, USA. · J Geriatr Psychiatry Neurol. · Pubmed #18004006 No free full text.

Abstract: Dementia and depression are frequently comorbid among older adult patients. Depression is related to cognitive decrement and can even represent the first signs of a neurodegenerative process. It can be difficult to distinguish depressed patients exhibiting the first signs of dementia from those whose cognition will improve with treatment. In this article, studies from the neuropsychological literature are reviewed that aid in accurate diagnosis and prognosis. Furthermore, the relationship between depression and dementia is explored by examining potential neurobiological mechanisms that may potentiate both syndromes in the context of the ongoing debate on depression as a prodrome and/or a risk factor for dementia. This article is concluded with suggestions for clinicians when deciding who to refer for neuropsychological assessment and with ideas for further research that might promote a better understanding of the complex association between depression and dementia during old age.