Alzheimer Disease: Brickman AM

Aisen PS, Marin DB, Brickman AM, Santoro J, Fusco M. · Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA. · Alzheimer Dis Assoc Disord. · Pubmed #11403336 No free full text.

Abstract: Anti-inflammatory drugs may be useful in the treatment of Alzheimer disease (AD). In preparation for therapeutic trials, we conducted pilot feasibility studies of hydroxychloroquine alone and in combination with colchicine in subjects with AD. A total of 20 subjects with probable AD were treated with hydroxychloroquine 200 mg twice daily for 11 weeks, or hydroxychloroquine 200 mg twice daily plus colchicine 0.6 mg twice daily for 12 weeks; subjects were monitored for adverse medical, cognitive, or behavioral effects. Neither regimen caused adverse effects on cognitive or behavioral assessment scores. There were no significant side effects in subjects receiving hydroxychloroquine alone; 2 subjects receiving the two drugs together experienced diarrhea. We conclude that these regimens of anti-inflammatory therapy are well tolerated in subjects with AD, indicating the feasibility of large-scale therapeutic trials of these agents.

Helzner EP, Luchsinger JA, Scarmeas N, Cosentino S, Brickman AM, Glymour MM, Stern Y. · Gertrude H. Sergievsky Center, Columbia University Medical Center, NY, New York, USA. · Arch Neurol. · Pubmed #19273753 No free full text.

Abstract: BACKGROUND: Vascular factors including medical history (heart disease, stroke, diabetes, and hypertension), smoking, and prediagnosis blood lipid measurements (cholesterol: total, high-density lipoprotein, low-density lipoprotein [LDL-C], and triglyceride concentrations) may be predictors for progression of Alzheimer disease (AD). OBJECTIVE: To determine whether prediagnosis vascular risk factors are associated with progression of AD. DESIGN: Inception cohort followed up longitudinally for a mean of 3.5 (up to 10.2) years. SETTING: Washington Heights/Inwood Columbia Aging Project, New York, New York. Patients One hundred fifty-six patients with incident AD (mean age at diagnosis, 83 years). Main Outcome Measure Change in a composite score of cognitive ability from diagnosis onward. RESULTS: In generalized estimating equation models (adjusted for age, race/ethnicity, and years of education), higher cholesterol (total cholesterol and LDL-C) concentrations and history of diabetes were associated with faster cognitive decline. Each 10-U increase in cholesterol and LDL-C was associated with a 0.10-SD decrease in cognitive score per year of follow-up (P < .001 for total cholesterol; P = .001 for LDL-C). High-density lipoprotein cholesterol and triglyceride concentrations were not associated with rate of decline. A history of diabetes was associated with an additional 0.05-SD decrease in cognitive score per year (P = .05). History of heart disease and stroke were associated with cognitive decline only in carriers of the apolipoprotein E epsilon4 (APOE-epsilon4) gene. In a final generalized estimating equation model that included high-density lipoprotein cholesterol and LDL-C concentrations and history of diabetes, only higher LDL-C was independently associated with faster cognitive decline. CONCLUSION: Higher prediagnosis total cholesterol and LDL-C concentrations and history of diabetes were associated with faster cognitive decline in patients with incident AD, which provides further evidence for the role of vascular risk factors in the course of AD.

Louis ED, Brickman AM, DeCarli C, Small SA, Marder K, Schupf N, Brown TR. · Unit 198, Department of Neurology, Columbia University, 710 W 168th St, New York, NY 10032, USA. · Arch Neurol. · Pubmed #19064753 links to  free full text

Abstract: BACKGROUND: Mild parkinsonian signs (MPS) are a marker of incident dementia. They have been linked with cerebrovascular disease, which can be evaluated using magnetic resonance imaging (MRI). Also, if MPS are a marker for developing Alzheimer-type changes, hippocampal volume on MRI might be diminished in individuals with MPS. OBJECTIVE: To examine white matter hyperintensity (WMH) volume and total hippocampal volume in elderly individuals with and without MPS. METHODS: Community-dwelling elderly persons in northern Manhattan (New York), New York, underwent neurologic examination and brain MRI. The WMH volume (derived from fluid-attenuated inversion recovery-weighted MRIs using a semiautomated thresholding approach) and total hippocampal volume (derived manually) were expressed relative to total cranial volume. RESULTS: Mild parkinsonian signs were present in 111 of 666 participants (16.7%). Mean (SD) relative WMH volume was larger in participants with MPS vs those without MPS (1.70 [1.28] vs 1.17 [1.18]; P<.001). In a multivariate logistic regression analysis adjusting for age, sex, race/ethnicity, years of educational achievement, and depression, relative WMH volume was associated with MPS (odds ratio, 1.26; 95% confidence interval, 1.08-1.47; P=.004). In both unadjusted and adjusted analyses, total relative hippocampal volume was similar in participants with MPS vs those without MPS regardless of cognitive status. CONCLUSIONS: In this MRI study of community-dwelling elderly persons, WMH volume was associated with MPS and total relative hippocampal volume was not. These data raise the possibility that vascular disease could have a role in the development of MPS.

Brickman AM, Honig LS, Scarmeas N, Tatarina O, Sanders L, Albert MS, Brandt J, Blacker D, Stern Y. · Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, 630 W 168th St, Campus Box 16, New York, NY 10032, USA. · Arch Neurol. · Pubmed #18779424 No free full text.

Abstract: OBJECTIVE: To determine if baseline measurements of cerebral atrophy and severity of white matter hyperintensity (WMH) predict the rate of future cognitive decline in patients with Alzheimer disease (AD). DESIGN: Data were drawn from the Predictors Study, a longitudinal study that enrolls patients with mild AD and reassesses them every 6 months with use of the Columbia modified Mini-Mental State (mMMS) examination (score range, 0-57). Magnetic resonance images were analyzed to determine the severity of WMH, using the Scheltens scale, and the degree of atrophy, using the bicaudate ratio. Generalized estimating equations were used to determine whether severity of baseline magnetic resonance image measurements and their interaction predicted the rate of mMMS score decline at subsequent visits. SETTING: Three university-based AD centers in the United States. PARTICIPANTS: At baseline, 84 patients with AD from the Predictors Study received structural magnetic resonance imaging and were selected for analysis. They had a mean of 6 follow-up evaluations. Main Outcome Measure The mMMS score. RESULTS: Generalized estimating equation models demonstrated that the degree of baseline atrophy (beta = -0.316; P = .04), the severity of WMH (beta = -0.173; P = .03), and their interaction (beta = -6.061; P = .02) predicted the rate of decline in mMMS scores. CONCLUSIONS: Both degree of cerebral atrophy and severity of WMH are associated with the rapidity of cognitive decline in AD. Atrophy and WMH may have a synergistic effect on future decline in AD, such that patients with a high degree of both have a particularly precipitous cognitive course. These findings lend further support to the hypothesis that cerebrovascular pathological abnormalities contribute to the clinical syndrome of AD.

Anderson KE, Brickman AM, Flynn J, Scarmeas N, Van Heertum R, Sackeim H, Marder KS, Bell K, Moeller JR, Stern Y. · Cognitive Neuroscience Division, Taub Institute for Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons of Columbia University, New York, NY, USA. · Neurology. · Pubmed #17538034 No free full text.

Abstract: OBJECTIVE: To characterize deficits in nonverbal recognition memory and functional brain changes associated with these deficits in Alzheimer disease (AD). METHODS: Using O-15 PET, we studied 11 patients with AD and 17 cognitively intact elders during the combined encoding and retrieval periods of a nonverbal recognition task. Both task conditions involved recognition of line drawings of abstract shapes. In both conditions, subjects were first presented a list of shapes as study items, and then a list as test items, containing items from the study list and foils. In the titrated demand condition, the shape study list size (SLS) was adjusted prior to imaging so that each subject performed at approximately 75% recognition accuracy; difficulty during PET scanning in this condition was approximately matched across subjects. A control task was used in which SLS = 1 shape. RESULTS: During performance of the titrated demand condition, SLS averaged 4.55 (+/-1.86) shapes for patients with AD and 7.53 (+/-4.81) for healthy elderly subjects (p = 0.031). However, both groups of subjects were closely matched on performance in the titrated demand condition during PET scanning with 72.17% (+/-7.98%) correct for patients with AD and 72.25% (+/-7.03%) for elders (p = 0.979). PET results demonstrated that patients with AD showed greater mean differences between the titrated demand condition and control in areas including the left fusiform and inferior frontal regions (Brodmann areas 19 and 45). CONCLUSIONS: Relative fusiform and inferior frontal differences may reflect the Alzheimer disease (AD) patients' compensatory engagement of alternate brain regions. The strategy used by patients with AD is likely to be a general mechanism of compensation, rather than task-specific.

Reitz C, Brickman AM, Luchsinger JA, Wu WE, Small SA, Tang MX. · Gertrude H. Sergievsky Center, Columbia University, New York, NY 10032, USA. · Am J Geriatr Cardiol. · Pubmed #17483671 links to  free full text

Abstract: The authors compared the frequency of structural and functional heart abnormalities assessed using transthoracic echocardiography among persons with Alzheimer's disease, vascular dementia, stroke, and healthy control subjects. Compared with controls, patients with Alzheimer's disease were more likely to have aortic valve thickening, aortic valve regurgitation, left ventricular wall motion abnormalities, left ventricular hypertrophy, and reduced ejection fraction. Persons with vascular dementia were more likely to have aortic valve regurgitation, but mitral valve thickening and tricuspid valve regurgitation were also more frequent. In the absence of dementia, persons with stroke differed from controls by more frequent mitral valve calcifications. With the increasing prevalence of Alzheimer's disease and vascular dementia, clinicians have to be more attentive to the presence of structural heart disease and its complications in persons with these conditions.

Stavitsky K, Brickman AM, Scarmeas N, Torgan RL, Tang MX, Albert M, Brandt J, Blacker D, Stern Y. · Gertrude H. Sergievsky Center and Department of Neurology, Columbia University Medical Center, New York, NY, USA. · Arch Neurol. · Pubmed #17030662 links to  free full text

Abstract: BACKGROUND: Although dementia with Lewy bodies (DLB) may be one of most common forms of dementia, relatively little is known about its cognitive and functional course. OBJECTIVE: To compare change over time in general cognitive status, memory test performance, psychiatric symptoms, neurological signs, and functional abilities in patients with probable DLB and probable Alzheimer disease (AD). DESIGN: Twenty-eight patients who met diagnostic criteria for DLB were recruited into the study from 3 sites. Patients with AD (n = 55) were selected from a larger cohort and matched 2 to 1 to the patients with DLB on age and baseline global cognitive status. Patients were followed up at 6-month intervals for an average of 6.2 visits and assessed at each visit with tests of global cognitive functioning and verbal learning and memory and measures of psychiatric, neurological, and functional status. RESULTS: At the baseline evaluation, patients with DLB performed more poorly on a measure of constructional praxis and all measures of functional status. They also had more severe psychiatric symptoms and neurological signs than the AD group. Despite these initial differences, generalized estimating equations applied to regression analyses with repeated measures determined that the only difference between the 2 groups in change in cognitive test performance was on a measure of recognition memory; patients with AD declined, while patients with DLB remained relatively stable. Patients with DLB had relatively stable behavioral symptoms and visual illusions, whereas patients with AD had a significant increase in these symptoms over time. Neurological and functional changes over time were similar in the 2 groups. CONCLUSIONS: Both baseline and longitudinal differences between patients with DLB and patients with AD were noted; these have implications for clinical diagnosis and treatment.

Samuels SC, Brickman AM, Burd JA, Purohit DP, Qureshi PQ, Serby M. · Department of Psychiatry, Box 1230, Mount Sinai School of Medicine, One East 100th Street, New York, NY 10029, USA. · Mt Sinai J Med. · Pubmed #14770251 links to  free full text

Abstract: Depression has frequently been cited as a manifestation of dementia with Lewy bodies (DLB). Previous studies have suggested an increase of depression in patients with DLB, compared to those with Alzheimer's disease (AD). The purpose of this study was to examine depressive symptomatology in nursing home residents, from a consecutive series of DLB (n=16) and AD (n=39) autopsy-confirmed cases. Subjects received standard neuropathological analysis and postmortem chart review for clinical assessment of depression. Depressive symptomatology did not differ between the AD and DLB groups, and there was no significant relationship between depression and cortical or subcortical Lewy body (LB) count in the locus ceruleus or substantia nigra. This study suggests that the presence or absence of depression cannot be used to distinguish between AD and DLB. Furthermore, depressive symptomatology in DLB does not appear to be related to severity of cortical or subcortical LB pathology.

Foldi NS, Brickman AM, Schaefer LA, Knutelska ME. · Department of Psychology, Queens College and The Graduate Center of The City University of New York, 65-30 Kissena Blvd., NSB-E318, Flushing, NY 11367, USA. · Psychiatry Res. · Pubmed #14500116 No free full text.

Abstract: Geriatric depression is associated with cognitive deficits that share similar features with Alzheimer's disease (AD) and normal aging. This study examined cognitive profiles and serial position effects in patients with geriatric depression (N=20) or AD (N=32) and in elderly controls (N=18). Groups were compared on two measures of serial position of the California Verbal Learning Test (CVLT), scaled scores and regional scores. Newly devised regional scores measure the percentage of items recalled as a function of the possible number of items presented from three regions of the list. Regional scores significantly differentiated depressed from control groups, with reduction of recalled items from the middle region. Scaled scores distinguished the depression from the AD groups on primacy and recency regions, with the characteristic recency effect seen in the AD group. Deficits in regional scores of the middle region are discussed in the context of lower resources in depression.

Serby M, Brickman AM, Haroutunian V, Purohit DP, Marin D, Lantz M, Mohs RC, Davis KL. · Departments of Psychiatry and Psychology, Mount Sinai School of Medicine, New York, NY, USA. · Am J Geriatr Psychiatry. · Pubmed #12724118 No free full text.

Abstract: OBJECTIVES: Authors compared the degrees of cognitive deficit among individuals with Alzheimer disease (AD), the Lewy-body variant of AD (LBV), and "pure" dementia with Lewy bodies (DLB); and compared cortical Lewy body (LB) counts in LBV versus DLB and neuritic plaque and neurofibrillary tangle severity in LBV versus AD. METHODS: Authors examined brain specimens from consecutive autopsies of elderly nursing home subjects. Numbers and densities of plaques, Lewy bodies, and tangle severity were determined in multiple cortical regions, and demographic and clinical variables were compared among the three groups. RESULTS: The three groups did not differ in demographic or clinical variables. The LBV group was significantly more impaired than the other groups. Cortical LB counts were significantly higher in LBV than in DLB. There was no evidence of increased plaque or tangle severity in LBV than in AD. CONCLUSION: The co-occurrence of AD and LB pathology is associated with higher numbers of LBs and more severe dementia than when classical AD or LB lesions occur alone.

Brickman AM, Riba A, Bell K, Marder K, Albert M, Brandt J, Stern Y. · Department of Neurology, Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA. · Arch Neurol. · Pubmed #12164728 links to  free full text

Abstract: BACKGROUND: The Dependence Scale measures the amount of assistance patients with dementia require in performing daily activities. Validity and reliability of this scale have been demonstrated, but the progression throughout long periods in patients with Alzheimer disease (AD) has not previously been examined. OBJECTIVE: To determine the longitudinal course of patient dependence in a cohort of prospectively followed AD patients. METHODS: Two hundred thirty AD patients enrolled in the Predictors Study were followed up prospectively at 6-month intervals for an average of 6.5 visits. The Dependence Scale was administered to a caregiver, and patients were assessed with the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia Rating Scale. Dependence level and the additive sum of the Dependence Scale items were considered for analysis. RESULTS: Generalized estimating equations to regression analyses were used to determine that both Dependence Scale scores and dependence level significantly decline with time. By covarying mMMSE scores and self-care deficits factor scores of the Blessed Dementia Rating Scale, generalized estimating equations analysis also demonstrated that change in patient dependence was independent of global cognitive decline and other measures of activities of daily living, respectively. CONCLUSIONS: This study shows the validity of the Dependence Scale and demonstrated that dependency in AD significantly declines with time independent of global cognition and other self-care deficits. The scale is a valuable instrument for outcomes research, efficacy trials, and behavioral research in AD.