Alzheimer Disease: Sano M

Marder K, Sano M. · No affiliation provided · Neurology. · Pubmed #10851358 No free full text.

This publication has no abstract.

Sano M. · Alzheimer's Disease Research Center, Mount Sinai School of Medicine, New York, NY, USA. · CNS Spectr. · Pubmed #18955963 links to  free full text

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Sano M, Grossman H, Van Dyk K. · The Alzheimer Disease Research Center of Mount Sinai School of Medicine, New York, New York, USA. · CNS Drugs. · Pubmed #18840031 No free full text.

Abstract: Alzheimer's disease is an ever-increasing health concern among the aging population, and as we research new and existing treatments for this disease we begin to uncover possibilities for its prevention. Observational studies and animal models have provided promising findings and generated excitement, but placebo-controlled clinical trials are required to demonstrate true efficacy for these treatments.In the past two decades, clinical trials have led to the approval of symptomatic treatments for Alzheimer's disease, including cholinesterase inhibitors and, more recently, an NMDA receptor antagonist. Clinical trials have also examined antioxidants, NSAIDs, hormone replacement, nutritional supplements and nonpharmacological interventions for the treatment and prevention of Alzheimer's disease. While the results of many of these trials have been disappointing, new mechanisms targeting the hallmark pathology of Alzheimer's disease are currently under investigation, including immunotherapy and secretase modulation, targeted at reducing the amyloid burden, for which we await the results. We review the evidence from completed trials, support for ongoing studies and propose directions for future research.

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.

Faison WE, Schultz SK, Aerssens J, Alvidrez J, Anand R, Farrer LA, Jarvik L, Manly J, McRae T, Murphy GM, Olin JT, Regier D, Sano M, Mintzer JE. · Alzheimer's Research and Clinical Programs, Neurosciences Department, Medical University of South Carolina, Charleston, South Carolina 29406, USA. · Int Psychogeriatr. · Pubmed #17451614 No free full text.

Abstract: OBJECTIVE: Despite numerous clinical trials, it is unknown whether ethnicity affects treatment response to cognitive enhancers in Alzheimer's disease (AD). There is convincing evidence of ethnic and genetic variability in drug metabolism. This article reviews the available data on ethnicity in clinical trials for AD to answer two questions: (1) what are the challenges to diagnose and treat AD across different ethnic groups, and (2) are there differences in response to pharmacologic interventions for AD across these different ethnic groups? METHOD: Available data from Alzheimer's Disease Cooperative Study (ADCS) randomized controlled clinical trials and from randomized controlled industry-sponsored trials for four cognitive enhancers (donepezil, galantamine, rivastigmine and sabeluzole) were pooled to assess the numbers of non-Caucasian participants. RESULTS: The participation of ethnic minority subjects in clinical trials for AD was dependent on the funding source, although Caucasian participants were over-represented and non-Caucasian participants were under-represented in the clinical trials. Because of the low participation rate of ethnic minorities, there were insufficient data to assess any differences in treatment outcome among different ethnic groups. Strategies to improve diversity in clinical trials are discussed. CONCLUSION: Greater participation of ethnically diverse participants in clinical trials for AD would generate additional information on possible differences in metabolism, treatment response, adverse events to therapeutic agents, and could foster the investigation of genetic variability among ethnic groups.

Aloysi A, Van Dyk K, Sano M. · The Alzheimer Disease Research Center, Mount Sinai School of Medicine, New York, NY, USA. · Mt Sinai J Med. · Pubmed #17195882 links to  free full text

Abstract: Recent interest in women's health has focused on the cognitive consequences of aging and hormonal changes. Based on hypotheses about estrogenic effects in the central nervous system (CNS), large-scale clinical trials were designed to address the efficacy of hormone replacement on protection against dementia and cognitive decline. Surprisingly, an absence of risk reduction for dementia and cognitive loss was found and much reanalysis of these findings has focused on timing of hormone replacement. Here we take a broad perspective to address a fuller range of psychological health. Gender differences in other psychiatric conditions including depression and anxiety have been attributed to hormones, and the neurotransmitter systems that are implicated in affective disorders may have an impact on cognitive impairment as well. Hormonal influences on neurotrophic mechanisms, as well as neurotransmitter effects, may be responsible for a breadth of neuropsychiatric conditions, particularly in aging. This review will focus on cognition, mood and anxiety issues among women with an emphasis on changes associated with aging. We will review data on the epidemiology of these entities and examine the biological mechanisms, which may be involved, with an emphasis on those mechanisms that may contribute to the multiple aspects of neuropsychiatry and women's health.

Geldmacher DS, Frolich L, Doody RS, Erkinjuntti T, Vellas B, Jones RW, Banerjee S, Lin P, Sano M. · Memory Disorders Program, Department of Neurology, University of Virginia, Box 800394, Charlottesville, Virginia 22908, USA. · J Nutr Health Aging. · Pubmed #17066215 No free full text.

Abstract: Alzheimer's disease (AD) is a progressive degenerative disease that warrants active management to delay or slow progression of its symptoms. The symptoms of AD encompass behavior and daily function as well as cognition, so clinicians should take a global view in the assessment of treatment success. Because there is currently no cure for AD, one cannot expect an initial cognitive improvement observed in the first few months of therapy to be sustained indefinitely. However, one should expect that the patient who is treated early and persistently with medication for AD will show less evidence of behavioral, functional, and cognitive deterioration over a period of time than one would expect in the absence of pharmacotherapy. Thus, treatment success includes not only short-term improvement of symptoms but also less decline over the long term. Determination of treatment success therefore also requires awareness of the typical progression of untreated AD. In this article we review the natural history of AD and evidence for the effectiveness of the treatments indicated for AD: donepezil, galantamine, rivastigmine, and memantine.

Bergmann C, Sano M. · Alzheimer Disease Research Center of Mount Sinai School of Medicine, NYC, James J Peters VAMC, Bronx, NY 10468, USA. · Neurol Res. · Pubmed #16945210 No free full text.

Abstract: Dementia is one of the commonest neurological disorders in the elderly population. In regards to the increasing longevity of populations worldwide, prevention of dementia has become a major public health challenge. There has been an intense research in the identification of modifiable risk factors for dementia. These risk factors could then be used as targets for intervention, pharmacologic or non-pharmacologic. Numerous reports of the relation between cardiovascular risk factors and cognitive decline and dementia have been published over the past years. This review focuses on the cardiovascular risk factors hypertension, hyperlipidemia and diabetes mellitus as targets for prevention of cognitive decline, overall dementia and Alzheimer's disease. Observational studies and clinical trials regarding the association between antihypertensive, lipid lowering and antidiabetic medications and the risk of impaired cognition, dementia or Alzheimer's disease are reviewed. Based on these data, we propose that early interventions at reducing these cardiovascular risk factors may have an impact on future incidence and prevalence of cognitive deficits of many etiologies including Alzheimer's disease.

Sano M. · Alzheimer Disease Research Center of Mount Sinai School of Medicine, New York, NY, USA. · J Geriatr Psychiatry Neurol. · Pubmed #16880357 No free full text.

Abstract: Neuropsychological testing can play a major role in the diagnosis of dementia by documenting cognitive deficits, the key criteria for the diagnosis. Because the most common dementia diagnosis, Alzheimer's disease, focuses on memory impairment, tests to assess this domain and to detect and characterize memory deficit are well established with recognized predictive value. Other neuropsychological domains are less well characterized and there are fewer tools to assess them. One domain that has been characterized as important in a number of other dementias is executive function. Improved neuropsychological assessment and characterization of other domains, such as executive function and attention, may assist in better identifying the pathophysiology of deficits in these areas, perhaps in combination with new technologies such as functional imaging. Finally, improved assessment tools for specific cognitive domains should assist in identifying a broad range of cognitive deficits at earlier stages and ultimately lead to more effective interventions for a wider range of cognitive deficits.

Sano M. · Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA. · CNS Spectr. · Pubmed #14702007 No free full text.

Abstract: Alzheimer's disease represents a significant challenge to the aging population. Since most estimates suggest that AD has a multifactorial etiology, the challenge to find preventative approaches is particularly great. With the aging of the population and the very high incidence from the eighth decade on, the challenge is further enhanced by the need to think of relatively safe interventions given the relative frailty of this elderly population. The need to find safe treatments, or ones with well-understood safety profiles, has led to the examination of known agents for potential dementia-preventing properties. Data supporting these interventions comes from observational studies, laboratory analyses, and clinical trials. Potential mechanisms for prevention of AD include anti-inflammatory and antioxidant approaches. Modulation of risk factors associated with cardiac disease may also reduce the risk of AD. Known agents have been examined for their potential to modify amyloid pathology. Trial designs to address prevention of AD include both primary and secondary prevention studies as well designs to assess slowing disease progression. Information can also be gathered when dementia evaluation is added to ongoing studies. As results from these studies becoming available, we will be able to refine our approach to managing this disease.

Sano M. · Bronx Veterans Medical Research Development, Bronx, NY 10468-3904, USA. · J Clin Psychiatry. · Pubmed #12934971 No free full text.

Abstract: Approved treatments for Alzheimer's disease have focused primarily on cholinergic enhancement. New attention, however, is being turned toward preventative treatments such as vitamin E, estrogen, and lipid-lowering agents. Preventative treatments focus on intervening prior to the onset of disease. These treatments are designed to modify the amyloid load. These new approaches require designs that select nonimpaired or minimally impaired populations, using new outcomes with prolonged assessment. The cost of these studies is high, but the potential benefit of delay or prevention of disease is the valuable goal.

Sano M. · Department of Neurology, College of Physicians and Surgeons of Columbia University, 630 W. 168th Street, Box 16, New York, NY 10032, USA. · Curr Neurol Neurosci Rep. · Pubmed #12169218 No free full text.

Abstract: Alzheimer's disease has been recognized as a major public health issue that will grow in prominence as life expectancy increases and as the shape of population demographics shifts toward expansion in the older age ranges with contraction in younger ages. The magnitude of the problem can be expressed in incidence, prevalence economics, and quality of life. Great strides have been made in understanding and treating this disease, but current clinical management is far from satisfactory and progression seems inevitable once the disease is diagnosed. Such forces in any disease encourage intervention strategies to move from treatment to prevention. However, this vision can only be met with reasonable success when pathology is understood and there is evidence that manipulation of that pathology leads to clinical benefit. This is the challenge that lies ahead to achieve the goal of prevention of Alzheimer's disease. This review begins by examining the progress that has been made in this disease. Current efforts to develop prevention strategies are described and possible agents for future evaluation are discussed.

Pappolla MA, Smith MA, Bryant-Thomas T, Bazan N, Petanceska S, Perry G, Thal LJ, Sano M, Refolo LM. · University of South Alabama, Mobile 36617, USA. · Free Radic Biol Med. · Pubmed #12106813 No free full text.

Abstract: Recent epidemiological, clinical, and experimental data suggest that cholesterol may play a role in Alzheimer's disease (AD). We have recently shown that cholesterolemia has a profound effect in the development and modulation of amyloid pathology in a transgenic model of AD. This review summarizes recent advancements in our understanding of the potential role of cholesterol and the amyloid beta protein in initiating the generation of free radicals and points out their role in a chain of events that causes damage of essential macromolecules in the central nervous system and culminates in neuronal dysfunction and loss. Experimental data links cholesterol and oxidative stress with some neurodegenerative aspects of AD.

Sano M. · Department of Neurology, Sergievsky Center and Taub Institute for Alzheimer's Disease Research, Columbia University, New York, NY 10032, USA. · J Neural Transm Suppl. · Pubmed #10961433 No free full text.

Abstract: There is growing evidence that post menopausal use of estrogen may have a beneficial effect on cognition and may reduce the risk of dementia. In a vast majority of studies, the use of estrogen replacement in the postmenopausal period was associated with a reduced risk of dementia. Meta-analyses of both retrospective case controlled and prospective studies indicate a 30% reduction in the risk of dementia, with larger effect sizes (50% reduction) reported in the latter. Some, but not all, large epidemiological studies indicate that estrogen use is associated with better performance on both verbal and visual memory testing in later life. However, studies of the effect of estrogen on patients with Alzheimer's disease are less convincing with minimal effects reported in open trials and following brief exposure. Biological mechanisms, which could be responsible for some of these effects, include activation of the cholinergic system, anti-oxidant action, neurotrophic stimulation and anti-amyloidogenic properties. Beneficial effects of estrogen in primary prevention but not secondary prevention of heart disease indicates that the ability to observe beneficial effects may depend on the point at which intervention occurs. Ongoing double-blind randomized clinical trial to determine if estrogen is a safe and effective treatment for the prevention of memory loss and Alzheimer's disease will be described. Future work will undoubtedly include the identification of specific estrogenic receptors in the central nervous system that can be selectively activated without adverse involvement of other biologic systems.

Desmond DW, Erkinjuntti T, Sano M, Cummings JL, Bowler JV, Pasquier F, Moroney JT, Ferris SH, Stern Y, Sachdev PS, Hachinski VC. · Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, New York, USA. · Alzheimer Dis Assoc Disord. · Pubmed #10609678 No free full text.

Abstract: Dementia is common among patients with cerebrovascular disease, particularly in a setting of one or more clinically evident strokes. Prior cohort and case studies have suggested that the cognitive syndrome of vascular dementia is characterized by predominant executive dysfunction, in contrast to the deficits in memory and language function that are typical of patients with Alzheimer disease. The course of cognitive decline may also differ between those dementia subtypes, with many, but not all, patients with vascular dementia exhibiting a stepwise course of decline caused by recurrent stroke and most patients with Alzheimer disease exhibiting a gradually progressive course of decline. The findings of prior studies of the cognitive syndrome of vascular dementia must be interpreted with caution, however, because of (1) possible inaccuracies in the determination of the dementia subtype and the loss of precision that might result from pooling heterogeneous subgroups of patients with vascular dementia, (2) difficulties inherent in identifying a pattern of strengths and weaknesses in patients who are required to have memory impairment and other deficits to meet operationalized criteria for dementia, and (3) the use of limited test batteries whose psychometric properties are incompletely understood. Specific questions that should be addressed by future studies are discussed.

Mayeux R, Sano M. · Taub Institute on Alzheimer's Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. · N Engl J Med. · Pubmed #10572156 No free full text.

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Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, Galasko D, Jin S, Kaye J, Levey A, Pfeiffer E, Sano M, van Dyck CH, Thal LJ, Anonymous00379. · Mayo Clinic College of Medicine, Rochester, Minn, USA. · N Engl J Med. · Pubmed #15829527 links to  free full text

Abstract: BACKGROUND: Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease. METHODS: In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function. RESULTS: A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E epsilon4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E epsilon4 carriers. CONCLUSIONS: Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo.

Grundman M, Petersen RC, Ferris SH, Thomas RG, Aisen PS, Bennett DA, Foster NL, Jack CR, Galasko DR, Doody R, Kaye J, Sano M, Mohs R, Gauthier S, Kim HT, Jin S, Schultz AN, Schafer K, Mulnard R, van Dyck CH, Mintzer J, Zamrini EY, Cahn-Weiner D, Thal LJ, Anonymous00151. · Alzheimer's Disease Cooperative Study, Department of Neurosciences, University of California-San Diego, 8950 Villa La Jolla Drive, Suite 227, La Jolla, CA 92037, USA. · Arch Neurol. · Pubmed #14732621 links to  free full text

Abstract: BACKGROUND: Mild cognitive impairment (MCI) represents a transitional state between the cognitive changes of normal aging and very early dementia and is becoming increasingly recognized as a risk factor for Alzheimer disease (AD). The Memory Impairment Study (MIS) is a multicenter clinical trial in patients with MCI designed to evaluate whether vitamin E or donepezil is effective at delaying the time to a clinical diagnosis of AD. OBJECTIVE: To describe the baseline characteristics of patients with MCI recruited for the MIS and compare them with those of elderly controls and patients with AD in another clinical trial. DESIGN: Descriptive and comparative study of patients with MCI participating in a multicenter clinical trial. SETTING: Memory disorder centers in the United States and Canada. PATIENTS: A total of 769 patients with MCI, 107 cognitively normal elderly controls, 122 patients with very mild AD (Clinical Dementia Rating [CDR] 0.5), and 183 patients with mild AD (CDR 1.0) were evaluated. Patients in the MIS met operational criteria for amnestic MCI. Controls were recruited in parallel with the MCI group, underwent the same assessments, and had a CDR of 0. MAIN OUTCOME MEASURES: Clinical, neuropsychologic, functional, neuroimaging, and genetic measures. RESULTS: Mean +/- SD Alzheimer's Disease Assessment Scale-Cognitive Subscale scores were 5.6 +/- 3.3 for controls, 11.3 +/- 4.4 for patients with MCI, 18.0 +/- 6.2 for the AD CDR 0.5 group, and 25.2 +/- 8.8 for the AD CDR 1.0 group. Compared with controls, patients with MCI were most impaired on memory tasks, with less severe impairments in other cognitive domains. Patients with MCI were more likely than controls but less likely than patients with AD to carry the apolipoprotein E epsilon4 allele. Patients with MCI had hippocampal volumes that were intermediate between those of controls and patients with AD. CONCLUSIONS: Patients with MCI had a predominant memory impairment with relative sparing of other cognitive domains and were intermediate between clinically normal individuals and patients with AD on cognitive and functional ratings. These results demonstrate the successful implementation of operational criteria for this unique group of at-risk patients in a multicenter clinical trial.

Sano M, Wilcock GK, van Baelen B, Kavanagh S. · Mount Sinai School of Medicine/Veterans Affairs Hospital, Bronx, NY 10468, USA. · Int J Geriatr Psychiatry. · Pubmed #14533127 No free full text.

Abstract: AIM: The aim of the study was to determine whether the clinical benefits of galantamine for patients with Alzheimer's disease lead to benefits for caregivers. METHODS: Data were pooled from two concurrent, multi-centre, randomized, double-blind, placebo-controlled, 6-month trials. Time caregivers spent assisting with activities of daily living (ADL) and time patients could be left unsupervised each day were assessed using the Allocation of Caregiver Time Survey. In total, 825 patients with mild-to-moderate Alzheimer's disease were included. RESULTS: At endpoint, caregivers of galantamine-treated patients were more likely to report reductions (41% vs 37%), maintenance (19% vs 14%) or smaller increases (26% vs 34% reporting an increase >30 minutes) in time assisting with ADL compared with the placebo group (p=0.026; Wilcoxon rank-sum test). The mean daily time difference was 32 minutes (p=0.011). Among patients with moderate Alzheimer's disease, caregivers of galantamine-treated patients were even more likely to report reductions (46% vs 37%), maintenance (15% vs 6%) or smaller increases (25% vs 42% for increases >30 min) vs placebo (p=0.004), with a mean daily time saving of 53 minutes (p=0.021). Caregivers of galantamine-treated patients were more likely to report increases (22% vs 18%), maintenance (45% vs 43%) or smaller reductions (30% vs 37% for reductions >30 minutes) in time the patient could be left unsupervised compared with placebo (p=0.027). Mean daily time saving was 27 minutes. Among patients with moderate Alzheimer's disease, the treatment effect was greater (p=0.029), with caregivers in the galantamine group reporting the change in time left unsupervised as 68 minutes longer each day than caregivers of patients receiving placebo. CONCLUSION: The clinical benefits of galantamine for patients with Alzheimer's disease are also associated with benefits to caregiving.

Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S, Thomas RG, Thal LJ, Anonymous00135. · Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. · JAMA. · Pubmed #12783912 links to  free full text

Abstract: CONTEXT: Laboratory evidence that inflammatory mechanisms contribute to neuronal injury in Alzheimer disease (AD), along with epidemiological evidence, suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence the course of the disease. OBJECTIVE: To determine whether treatment with a selective cyclooxygenase (COX) -2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows cognitive decline in patients with mild-to-moderate AD. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to study medications. SETTING: Forty ambulatory treatment centers affiliated with the Alzheimer's Disease Cooperative Study consortium. PARTICIPANTS: Participants with mild-to-moderate AD (Mini-Mental State Examination score of 13-26) were recruited from December 1999 to November 2000 using clinic populations, referrals from community physicians, and local advertising. Stable use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin E was allowed. Participants with inflammatory diseases that might respond to the study medications were excluded. Of 474 participants screened, 351 were enrolled. INTERVENTIONS: Once-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg, or placebo. MAIN OUTCOME MEASURES: The primary outcome measure was the 1-year change in the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric Inventory, the Quality of Life-AD, and the time to attainment of significant end points (4-point decline from baseline ADAS-Cog score, 1-step worsening on the global Clinical Dementia Rating scale, 15-point decline on the ADCS activities of daily living inventory, institutionalization, or death). RESULTS: The 1-year mean (SD) change in ADAS-Cog scores in participants treated with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different from the change in participants treated with placebo (5.7 [8.2]). Results of secondary analyses showed no consistent benefit of either treatment. Fatigue, dizziness, and hypertension were more commonly reported in the active drug groups, and more serious adverse events were found in the active treatment group than in the placebo group. CONCLUSION: The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.

Aisen PS, Egelko S, Andrews H, Diaz-Arrastia R, Weiner M, DeCarli C, Jagust W, Miller JW, Green R, Bell K, Sano M. · Department of Neurology, Georgetown University Medical Center, Washington, DC 20007, USA. · Am J Geriatr Psychiatry. · Pubmed #12611755 No free full text.

Abstract: OBJECTIVE: Authors determined the impact of high-dose vitamin supplements on plasma homocysteine levels in patients with Alzheimer disease (AD). METHODS: Authors used an open-label trial of folic acid, vitamin B(12), and vitamin B(6), in combination for 8 weeks, with measurement of plasma homocysteine levels in the fasting state and after methionine-loading. A total of 69 subjects with AD were enrolled, including 33 who were taking standard multivitamin supplements; 66 were available at 8-week follow-up. RESULTS: The high-dose vitamin regimen was associated with a significant reduction in fasting and post-methionine-loading homocysteine. Reductions were greater in the subgroup not using multivitamins, but were also significant in the multivitamin users. CONCLUSION: High-dose vitamin supplementation reduces homocysteine levels in patients with AD. The effect of supplementation on rate of cognitive decline will be assessed later in a randomized, double-blind study.

Thal LJ, Thomas RG, Mulnard R, Sano M, Grundman M, Schneider L. · Department of Neurosciences, University of California, San Diego, School of Medicine, 9500 Gilman Dr, La Jolla, CA 92093, USA. · Arch Neurol. · Pubmed #12580705 links to  free full text

Abstract: OBJECTIVE: To investigate whether an association exists between estradiol and estrone levels and measures of cognitive functioning in women with Alzheimer disease (AD) treated with conjugated equine estrogen (Premarin; Wyeth-Ayerst, Philadelphia, Pa). METHODS: We studied 120 postmenopausal women who underwent hysterectomy and who had AD treated with Premarin for 1 year. Plasma estradiol and estrone levels were determined at multiple points during the 1-year treatment trial. The change from baseline level at 2 and 12 months was associated with the change score on 7 different assessments of cognitive functioning. RESULTS: At baseline, estradiol levels were low and there were no associations between the estradiol level and the 7 neuropsychological measures. A similar pattern was observed for estrone treatment. During treatment with 0.625 mg/d of Premarin, estradiol levels increased about 4-fold; while receiving 1.25 mg/d of Premarin, estradiol levels increased about 8-fold. A similar pattern was seen with estrone treatment. For both estradiol and estrone levels, there were no significant associations between the change in plasma level and the change in neuropsychological test scores at either 2 or 12 months. CONCLUSION: Although Premarin elevated estradiol and estrone levels, there was no association between hormone levels and cognitive functioning after either 2 or 12 months of treatment.

Aisen PS, Berg JD, Craft S, Peskind ER, Sano M, Teri L, Mulnard RA, Thomas RG, Thal LJ. · Department of Neurology, Georgetown University Medical Center, 1Bles Building, 3800 Reservoir Road NW, Washington, DC 20007, USA. · Psychoneuroendocrinology. · Pubmed #12445840 No free full text.

Abstract: Glucose and insulin may play an important role in the pathophysiology and symptomatology of Alzheimers disease (AD), and prior studies suggest interactions among glucose, insulin, gender and apolipoprotein E genotype. We analyzed the relationship between steroid-induced glucose elevation and gender, presence of the apolipoprotein E epsilon 4 (APOE-4) allele and cognition using data from a multicenter trial of prednisone therapy in AD. The low-dose prednisone regimen (initial dose: 20 mg/day, maintenance dose: 10 mg/day) caused a moderate increase in random blood glucose (mean post-baseline glucose 115 mg/dl). There was a significant interaction between rise in glucose, gender and presence of the APOE-4 allele. There was no important relationship between glucose and cognitive function at baseline or with prednisone treatment. Meta-analysis including data from three other AD trials showed a small influence of random blood glucose on cognitive scores. These results support a relationship between gender, apolipoprotein E genotype and glucose metabolism, but do not indicate that mild changes in glucose have an important impact on cognitive function.

Weiner MF, Tractenberg RE, Sano M, Logsdon R, Teri L, Galasko D, Gamst A, Thomas R, Thal LJ. · Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, USA. · J Geriatr Psychiatry Neurol. · Pubmed #12083600 No free full text.

Abstract: Th determine if teaching caregivers behavior management techniques (BMTs) reduces long-term psychotropic use in Alzheimer's disease (AD) patients, we examined 12-month follow-up data from a 4-month randomized study comparing placebo, BMTs, trazodone, and haloperidol for the treatment of agitated behaviors in persons with AD. After 4 months, treatment was allowed with any agent. Between 42.8% and 51% of AD patients received additional psychotropics between 4 and 12 months. The relative risk of being prescribed any psychotropic drug after the 4-month trial was at or about 1.0 for subjects in each drug arm or placebo arm versus BMTs. We concluded that teaching caregivers BMTs did not diminish long-term prescription of psychotropic drugs.

Teri L, Logsdon RG, Peskind E, Raskind M, Weiner MF, Tractenberg RE, Foster NL, Schneider LS, Sano M, Whitehouse P, Tariot P, Mellow AM, Auchus AP, Grundman M, Thomas RG, Schafer K, Thal LJ, Anonymous00040. · University of Washington, Department of Psychosocial and Community Health, Seattle 98195-7263, USA. · Neurology. · Pubmed #11087767 No free full text.

Abstract: BACKGROUND: Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs. OBJECTIVE: To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients. METHODS: A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden. RESULTS: Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments. CONCLUSIONS: Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.