Alzheimer Disease: Rabins PV

Anonymous00207, Rabins PV, Blacker D, Rovner BW, Rummans T, Schneider LS, Tariot PN, Blass DM, Anonymous00208, McIntyre JS, Charles SC, Anzia DJ, Cook IA, Finnerty MT, Johnson BR, Nininger JE, Schneidman B, Summergrad P, Woods SM, Berger J, Cross CD, Brandt HA, Margolis PM, Shemo JP, Blinder BJ, Duncan DL, Barnovitz MA, Carino AJ, Freyberg ZZ, Gray SH, Tonnu T, Kunkle R, Albert AB, Craig TJ, Regier DA, Fochtmann LJ. · No affiliation provided · Am J Psychiatry. · Pubmed #18340692 No free full text.

This publication has no abstract.

Rabins PV, Lyketsos CG. · No affiliation provided · Nat Clin Pract Neurol. · Pubmed #17479071 No free full text.

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Munro CA, Brandt J, Sheppard JM, Steele CD, Samus QM, Steinberg M, Rabins PV, Lyketsos CG. · Division of Medical Psychology, Department of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA. · Am J Geriatr Psychiatry. · Pubmed #15353387 No free full text.

Abstract: OBJECTIVE: The authors assessed the cognitive effects of depression treatment with sertraline in patients with Alzheimer disease (AD) and major depression. METHODS: Forty-four patients with probable AD and major depression were enrolled in a double-blind, placebo-controlled clinical trial of sertraline. Cognitive testing was done at baseline and at 3-week intervals throughout the 12-week study. At the 12th week, subjects were categorized by treatment response (full, partial, or no response). Cognitive data from 41 participants who completed three or more testing sessions and 36 who completed all five study visits were included in the analyses. RESULTS: Neither improved mood nor use of sertraline was associated with cognitive change over time in AD patients. Post-hoc exploration of the data, however, suggested a sex difference in cognitive response to sertraline such that women treated with sertraline demonstrated improved cognition compared with women on placebo, whereas men treated with sertraline worsened significantly in cognition compared with men on placebo. CONCLUSIONS: In this study, among depressed AD patients after treatment with sertraline or placebo, there was no evidence that improved mood was associated with cognitive improvement. Future studies aimed at increasing power to detect mood as well as medication effects will be valuable in determining the relationship between cognition and treatment of depression in AD patients.

Lyketsos CG, DelCampo L, Steinberg M, Miles Q, Steele CD, Munro C, Baker AS, Sheppard JM, Frangakis C, Brandt J, Rabins PV. · Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA. · Arch Gen Psychiatry. · Pubmed #12860778 links to  free full text

Abstract: CONTEXT: Major depression affects about 25% of the patients who have Alzheimer disease and has serious adverse consequences for patients and caregivers. Results of prior antidepressant treatment studies have produced contradictory findings and have not fully assessed the benefits of depression reduction. OBJECTIVES: To assess the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease, and to evaluate the effect of depression reduction on activities of daily living, cognition, and nonmood behavioral disturbance. DESIGN: Randomized, placebo-controlled, parallel, 12-week, flexible-dose clinical trial with a 1-week, single-blind placebo phase. The study was conducted between January 1, 1998, and July 19, 2001. SETTING: University outpatient clinic. PARTICIPANTS: Forty-four outpatients who have probable Alzheimer disease and major depressive episodes. INTERVENTION: Sertraline hydrochloride, mean dosage of 95 mg/d, or identical placebo, randomly assigned. MAIN OUTCOME MEASURES: Response rate, Cornell Scale for Depression in Dementia, Hamilton Depression Rating Scale, Mini-Mental State Examination, Psychogeriatric Depression Rating Scale-activities of daily living subscale, and Neuropsychiatric Inventory to quantify patient behavior disturbance and caregiver distress. RESULTS: In the sertraline-treated group 9 patients (38%) were full responders and 11 (46%) were partial responders compared with 3 (20%) and 4 (15%), respectively, in the placebo-treated group (P =.007). The sertraline-treated group had greater improvements in the scores for the Cornell Scale for Depression in Dementia (P =.002) and Hamilton Depression Rating Scale (P =.01), and a statistical trend toward less decline in activities of daily living on the Psychogeriatric Depression Rating Scale-activities of daily living subscale (P =.07). There was no difference between the treatment groups in Mini-Mental State Examination (P =.22) or Neuropsychiatric Inventory (P =.32) ratings over time. When full responders, partial responders, and nonresponders were compared, full responders only, or full and partial responders had significantly better ratings on activities of daily living (P =.04), behavioral disturbance (P =.01), and caregiver distress (P =.006), but not on the Mini-Mental State Examination (P =.76). Safety monitoring indicated few differences in adverse effects between the 2 treatment groups. CONCLUSIONS: Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease. Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living, but not improved cognition.

Schneider LS, Tariot PN, Lyketsos CG, Dagerman KS, Davis KL, Davis S, Hsiao JK, Jeste DV, Katz IR, Olin JT, Pollock BG, Rabins PV, Rosenheck RA, Small GW, Lebowitz B, Lieberman JA. · Clinical Antipsychotic Trials of Intervention Effectiveness Program of the National Institute of Mental Health at the University of North Carolina, Chapel Hill, NC, USA. · Am J Geriatr Psychiatry. · Pubmed #11739062 No free full text.

Abstract: The authors describe the development of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) protocol for Alzheimer disease (AD), a trial developed in collaboration with the National Institute of Mental Health (NIMH), assessing the effectiveness of atypical antipsychotics for psychosis and agitation occurring in AD outpatients. They provide an overview of the methodology utilized in the trial as well as the clinical-outcomes and effectiveness measures that were implemented.

Lyketsos CG, Sheppard JM, Steele CD, Kopunek S, Steinberg M, Baker AS, Brandt J, Rabins PV. · Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, USA. · Am J Psychiatry. · Pubmed #11007727 links to  free full text

Abstract: OBJECTIVE: This study evaluated the efficacy and safety of sertraline in the treatment of major depression in 22 outpatients with Alzheimer's disease. METHOD: Twelve of the 22 patients were given sertraline and 10 were given placebo by random group assignment for 12 weeks. Response to treatment was measured by using the Cornell Scale for Depression in Dementia. The patients were also assessed with the Hamilton Depression Rating Scale, the activities of daily living subscale of the Psychogeriatric Dependency Rating Scales, and the Mini-Mental State. RESULTS: After 12 weeks of double-blind, placebo-controlled treatment, nine of the patients given sertraline and two of those given placebo were at least partial responders. Patients given sertraline had significantly greater mean declines from baseline in Cornell Scale for Depression in Dementia scores; the bulk of antidepressant response occurred by the third week of treatment. CONCLUSIONS: Sertraline is superior to placebo in reducing depression in patients with Alzheimer's disease who also suffer from major depression.

Rosenberg PB, Mielke MM, Tschanz J, Cook L, Corcoran C, Hayden KM, Norton M, Rabins PV, Green RC, Welsh-Bohmer KA, Breitner JC, Munger R, Lyketsos CG. · Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA. · Am J Geriatr Psychiatry. · Pubmed #18978249 links to  free full text

Abstract: BACKGROUND: Evidence suggests that cardiovascular medications, including statins and antihypertensive medications, may delay cognitive decline in patients with Alzheimer dementia (AD). We examined the association of cardiovascular medication use and rate of functional decline in a population-based cohort of individuals with incident AD. METHODS: In the Dementia Progression Study of the Cache County Study on Memory, Health, and Aging, 216 individuals with incident AD were identified and followed longitudinally with in-home visits for a mean of 3.0 years and 2.1 follow-up visits. The Clinical Dementia Rating (CDR) was completed at each follow-up. Medication use was inventoried during in-home visits. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes (CDR-Sum) as the outcome and cardiovascular medication use as the major predictors. RESULTS: CDR-Sum increased an average of 1.69 points annually, indicating a steady decline in functioning. After adjustment for demographic variables and the baseline presence of cardiovascular conditions, use of statins (p = 0.03) and beta-blockers (p = 0.04) was associated with a slower annual rate of increase in CDR-Sum (slower rate of functional decline) of 0.75 and 0.68 points respectively, while diuretic use was associated with a faster rate of increase in CDR-Sum (p = 0.01; 0.96 points annually). Use of calcium-channel blockers, angiotensin-converting enzyme inhibitors, digoxin, or nitrates did not affect the rate of functional decline. CONCLUSIONS: In this population-based study of individuals with incident AD, use of statins and beta-blockers was associated with delay of functional decline. Further studies are needed to confirm these results and to determine whether treatment with these medications may help delay AD progression.

Mielke MM, Rosenberg PB, Tschanz J, Cook L, Corcoran C, Hayden KM, Norton M, Rabins PV, Green RC, Welsh-Bohmer KA, Breitner JC, Munger R, Lyketsos CG. · Johns Hopkins University School of Medicine, Department of Psychiatry, Division of Geriatric Psychiatry and Behavioral Sciences, 550 N. Broadway, Suite 308, Baltimore, MD 21205, USA. · Neurology. · Pubmed #17984453 No free full text.

Abstract: BACKGROUND: While there is considerable epidemiologic evidence that cardiovascular risk factors increase risk of incident Alzheimer disease (AD), few studies have examined their effect on progression after an established AD diagnosis. OBJECTIVE: To examine the effect of vascular factors, and potential age modification, on rate of progression in a longitudinal study of incident dementia. METHODS: A total of 135 individuals with incident AD, identified in a population-based sample of elderly persons in Cache County, UT, were followed with in-home visits for a mean of 3.0 years (range: 0.8 to 9.5) and 2.1 follow-up visits (range: 1 to 5). The Clinical Dementia Rating (CDR) Scale and Mini-Mental State Examination (MMSE) were administered at each visit. Baseline vascular factors were determined by interview and physical examination. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes (CDR-Sum) or MMSE as the outcome, and vascular index or individual vascular factors as independent variables. RESULTS: Atrial fibrillation, systolic hypertension, and angina were associated with more rapid decline on both the CDR-Sum and MMSE, while history of coronary artery bypass graft surgery, diabetes, and antihypertensive medications were associated with a slower rate of decline. There was an age interaction such that systolic hypertension, angina, and myocardial infarction were associated with greater decline with increasing baseline age. CONCLUSION: Atrial fibrillation, hypertension, and angina were associated with a greater rate of decline and may represent modifiable risk factors for secondary prevention in Alzheimer disease. The attenuated decline for diabetes and coronary artery bypass graft surgery may be due to selective survival. Some of these effects appear to vary with age.

Chan DC, Kasper JD, Black BS, Rabins PV. · Harvard Geriatric Medicine Fellowship Program, Boston, Massachusetts, USA. · J Geriatr Psychiatry Neurol. · Pubmed #17548780 No free full text.

Abstract: Little is known about the prevalence and correlates of psychotropic drug use in community-dwelling elders with dementia. Baseline data from 285 community-dwelling elders with a research classification of dementia enrolled in the observational Memory and Medical Care Study were analyzed. Of these, 33.3% with a research classification of dementia were clinically diagnosed, 28.8% used at least 1 psychotropic drug, and 61.8% had at least 1 behavioral or psychologic symptom of dementia. Presence of a behavioral or psychologic symptom of dementia was associated with a higher likelihood of a clinical diagnosis of dementia. A clinical diagnosis of dementia, not a behavioral or psychologic symptom of dementia, was associated with psychotropics use. Clinical recognition of dementia appears to be an intermediate step between presence of symptoms of dementia and the prescription of psychotropics. Most community-dwelling elders meeting the research criteria for dementia were not clinically diagnosed, despite contact with a physician (89%) in the previous year.

Rabins PV, Black BS. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, and The Johns Hopkins Hospital, Baltimore, MD 21287, USA. · Int Psychogeriatr. · Pubmed #17346364 No free full text.

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Martin BK, Frangakis CE, Rosenberg PB, Mintzer JE, Katz IR, Porsteinsson AP, Schneider LS, Rabins PV, Munro CA, Meinert CL, Niederehe G, Lyketsos CG. · Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · Am J Geriatr Psychiatry. · Pubmed #17068314 No free full text.

Abstract: OBJECTIVE: Research on the efficacy of antidepressant therapy for depressive symptoms in Alzheimer disease has been hampered by lack of systematic diagnosis, small sample sizes, and short-term follow up. To address these issues, the authors present the design of the Depression in Alzheimer's Disease Study-2 (DIADS-2), a randomized, placebo-controlled multicenter trial to evaluate the efficacy and safety of the selective serotonin reuptake inhibitor sertraline for the treatment of depression in people with Alzheimer disease. METHODS: The authors present and discuss the following important aspects of the design: the inclusion of structured psychosocial therapy for the caregivers of all participants; the measurement not only of patient mood outcomes, but also of global and functional outcomes for patients and mood and burden outcomes for caregivers; the ongoing rating of multiple diagnostic criteria to allow nosologic study of depression in Alzheimer disease; the evaluation of both short-term efficacy and longer-term outcomes; the follow up of all patients regardless of whether they complete study treatment; and the unmasking of treatment assignment at the conclusion of each patient's treatment phase. CONCLUSIONS: The authors believe these design elements are important features to be included in trials of depression and other neuropsychiatric disturbances in Alzheimer disease.

Rabins PV, Lyketsos CG. · Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, MD 21287, USA. · Nat Clin Pract Neurol. · Pubmed #17057739 No free full text.

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Samus QM, Rosenblatt A, Onyike C, Steele C, Baker A, Harper M, Brandt J, Mayer L, Rabins PV, Lyketsos CG. · The Johns Hopkins School of Medicine, 550 North Broadway, Baltimore, MD 21205, USA. · J Gerontol B Psychol Sci Soc Sci. · Pubmed #16960235 No free full text.

Abstract: We used a cross-sectional study to examine the correlates of caregiver-rated quality of life (QOL) in 198 randomly selected residents from a stratified random sample of 22 assisted living facilities in central Maryland. We measured QOL by using the Alzheimer's Disease-Related Quality of Life Questionnaire. In general, despite cognitive impairment, residents in assisted living were rated as having a high QOL. In a multivariate regression, we found that nonmood neuropsychiatric symptoms were the strongest correlate of QOL, explaining 37% of the variance. Depressive symptoms, functional dependence, marital status, and cognition also contributed to the model, but only minimally. Because of the strong association of neuropsychiatric symptoms with QOL, special attention should be given to their recognition and amelioration.

Mayer LS, Bay RC, Politis A, Steinberg M, Steele C, Baker AS, Rabins PV, Lyketsos CG. · Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD 21287, USA. · Int J Geriatr Psychiatry. · Pubmed #16955427 No free full text.

Abstract: CONTEXT: Major depression affects about 25% of patients with Alzheimer's disease (AD) and has serious adverse consequences for patients as well as caregivers. Studies of treatments for depression in AD, like most treatment studies, depend on the ability of the scales used to measure outcome to detect a difference between the effects of treatment and control, particularly in trials conducted over waves. OBJECTIVE: To compare the ability of three depression scales, and some of their subscales, to detect the difference in the effects of drug (treatment) and placebo (control). DESIGN: Comparison of three scales of depression in terms of percent variance explained as indicated by the adjusted or partial eta-squared for the effect of drug versus placebo, controlling for baseline depression, in a randomized, placebo-controlled, parallel, 12-week, clinical trial of sertraline for the treatment of depression with AD. SETTING: University outpatient clinic. PARTICIPANTS: Forty-four patients with probable Alzheimer's disease and Major Depressive Episode. OUTCOME MEASURES: The Cornell Scale for Depression in Dementia (CSDD), the Hamilton Depression Rating Scale (HDRS), and the Neuropsychiatric-Inventory Mood Domains (NPI-M). RESULTS: Examination of the treatment effects as indicated by the partial eta-squared's for each scale at each wave, revealed a slight, but not significant, advantage for the use of the CSDD over the HDRS, and a significant advantage for the use of either of these over the NPI-M. Treatment effects, as reflected in the partial eta-squared's computed for the subscales at each wave, were significant for all four subscales, and were largest for the CSDD 'mood' subscale although they were not significantly greater than for the other subscales. CONCLUSIONS: The CSDD, and particularly its mood subscale, appears to be more sensitive than the HDRS, it's subscales or the NPI-M, for comparing drug to placebo in treating major depression in AD patients. Treatment effects as reflected in the partial eta-squared's were largest on the CSDD mood subscale and increased over time. The pattern for the other subscales was non-monotonic over waves and resembled the pattern for the entire scale. Perhaps combining the CSDD two subscales obscures the treatment effects for the separate subscales.

Lyketsos CG, Toone L, Tschanz J, Rabins PV, Steinberg M, Onyike CU, Corcoran C, Norton M, Zandi P, Breitner JC, Welsh-Bohmer K, Anthony J, Østbye T, Bigler E, Pieper C, Burke J, Plassman B, Green RC, Steffens DC, Klein L, Leslie C, Townsend JJ, Wyse BW, Munger R, Williams M, Anonymous00077. · Division of Geriatric Psychiatry and Neuropsychiatry, Dept. of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Johns Hopkins Hospital, Baltimore, MD 21287, USA. · Am J Geriatr Psychiatry. · Pubmed #16085781 No free full text.

Abstract: OBJECTIVE: Authors investigated medical comorbidity in persons with dementia and "Cognitive Impairment, No Dementia" (CIND). METHODS: The Cache County Study is an ongoing population-based study of the epidemiology of dementia, the risk factors for conversion from CIND to dementia, and the progression of dementia. As part of the study's first incidence wave, persons with dementia (N=149), CIND (N=225), or without cognitive impairment (N=321) were identified and studied. Participants received comprehensive clinical evaluations and were rated on the General Medical Health Rating (GMHR), a global measure of seriousness of medical comorbidity. Participants and informants also completed the Mini-Mental State Exam and provided self-report information about comorbid medical conditions and functioning in activities of daily living. RESULTS: There were few differences in number or type of comorbid medical conditions between persons with CIND and dementia, but persons with dementia were prescribed more medications. Stroke was more common in dementia participants, but other illnesses common in old age were not significantly different across cognitive groups. Medical comorbidity was more serious in both dementia and CIND, such that both groups were less likely to have "little to no" comorbidity. Seriousness of medical comorbidity was significantly associated with worse day-to-day functioning and cognition. CONCLUSIONS: Persons with CIND and dementia have more serious medical comorbidity than comparable persons without cognitive impairment. This comorbidity may play a role in the progression of CIND and dementia. Future studies should investigate the role of medical comorbidity and its treatment on dementia onset or progression, as well as the mechanisms mediating its neuropathologic effects.

Rosenberg PB, Onyike CU, Katz IR, Porsteinsson AP, Mintzer JE, Schneider LS, Rabins PV, Meinert CL, Martin BK, Lyketsos CG, Anonymous00389. · Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. · Int J Geriatr Psychiatry. · Pubmed #15660424 No free full text.

Abstract: OBJECTIVES: 'Depression of Alzheimer's Disease' (dAD) is a common complication of Alzheimer's disease and is increasingly recognized as a syndrome with a clinical presentation differing from major depression. Criteria for the diagnosis of dAD have been proposed previously. METHODS: This paper presents these criteria in operationalized format designed to be accessible for clinical use. Four cases are discussed that demonstrate the use of these criteria and illustrate important differences between dAD and major depression. RESULTS: The dAD criteria are broader than DSM-IV criteria for Major Depressive Episode and incorporate caregiver input. CONCLUSIONS: Given the differences between dAD and major depression diagnoses, it is important to assess the efficacy of treatments for dAD. Depression in Alzheimer's Disease-2 (DIADS-2) is a controlled trial of dAD treatments that will also assess the validity of these criteria.

Blass DM, Hatanpaa KJ, Brandt J, Rao V, Steinberg M, Troncoso JC, Rabins PV. · Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Neurology. · Pubmed #15304580 No free full text.

Abstract: OBJECTIVE: To characterize the clinical course of pathologically diagnosed hippocampal sclerosis dementia (HSD). BACKGROUND: Dementia associated with HSD is incompletely characterized. Previous studies suggest similarities to both Alzheimer disease (AD) and frontotemporal dementia (FTD). METHODS: Case-control analysis of the clinical course of patients with HSD, FTD, and AD from a neuropathology autopsy series conducted by a university hospital. Case histories were reviewed. Cumulative prevalence of behavioral, cognitive, psychiatric, and language symptoms were compared between groups, as was time of symptom onset. Clinical diagnostic criteria for FTD and AD were applied to case histories. Sensitivity and specificity of clinical FTD diagnostic criteria (Report of the Work Group on FTD and Pick's disease) were computed. RESULTS: Cumulative prevalence of symptoms in HSD was most similar to that of FTD and differed from AD. Behavioral abnormalities such as decreased grooming and inappropriate behavior were more prevalent in HSD and FTD than AD. Hyperorality, inappropriate behavior, and decreased interest had earlier onset in HSD and FTD. Cognitive symptoms of disorientation, dyscalculia, apraxia, and agnosia were more prevalent in AD, as were psychiatric symptoms of hallucinations, delusions, and aggression. Most HSD patients met diagnostic criteria for FTD. Criteria sensitivity was 64.0% and specificity was 73.7%. CONCLUSIONS: FTD is a clinical syndrome associated with heterogeneous neuropathology. The clinical course of HSD is more similar to that of FTD than AD. These findings, together with the neuropathologic data presented in the accompanying article, support expanding the scope of FTD (Pick complex) to include HSD.

Rabins PV. · John Hopkins Medical Institutions, Baltimore, MD, USA. · Georgia Law Rev. · Pubmed #15119323 No free full text.

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Olin JT, Schneider LS, Katz IR, Meyers BS, Alexopoulos GS, Breitner JC, Bruce ML, Caine ED, Cummings JL, Devanand DP, Krishnan KR, Lyketsos CG, Lyness JM, Rabins PV, Reynolds CF, Rovner BW, Steffens DC, Tariot PN, Lebowitz BD. · Adult and Geriatric Treatment and Preventive Interventions Research Branch, National Institute of Mental Health, Bethesda, MD 20892-9635, USA. · Am J Geriatr Psychiatry. · Pubmed #11925273 No free full text.

Abstract: The authors, a group of investigators with extensive research and clinical experience related to both late-life depression and Alzheimer disease (AD), propose provisional affective and behavioral inclusion and exclusion diagnostic criteria for Depression of AD.

Lyketsos CG, Breitner JC, Rabins PV. · Neuropsychiatry and Geriatric Psychiatry Services, School of Medicine, and Department of Mental Hygiene, School of Public Health, The Johns Hopkins University, Baltimore, Maryland, USA. · Int J Geriatr Psychiatry. · Pubmed #11746649 No free full text.

This publication has no abstract.