Alzheimer Disease: Zamrini E

Zamrini E, De Santi S, Tolar M. · Department of Neurology, 454 Sparks Center, 1720 7th Avenue South, University of Alabama at Birmingham, Birmingham, AL 35294, USA. · Neurobiol Aging. · Pubmed #15172748 No free full text.

Abstract: Alzheimer's disease (AD) starts at a molecular level possibly decades earlier than could be detected by neuropsychological tests (NPTs). Neuropathological and neuroimaging data suggest that amyloid accumulation precedes the clinical onset of AD. Disease-modifying agents would have to be used early to alter the course of AD. Therefore, preclinical diagnosis is necessary. Structural and functional neuroimaging are superior for detection of the earliest stages of AD. Magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques, including amyloid visualization, will have therapeutic importance for prevention as well as intervention as further refinements of current imaging techniques and biochemical markers occur. Neuropsychological tests measure the effect of pathology for an individual based upon norms obtained from an artificial population-often white and relatively highly educated. Unless serial NPTs are performed, the individual is compared to a population to which they may not conform. Neuroimaging can provide objective measures of preclinical disease state and, when measured serially, rate of change. Such information can be used in prevention trials.

Thal LJ, Grundman M, Berg J, Ernstrom K, Margolin R, Pfeiffer E, Weiner MF, Zamrini E, Thomas RG. · Department of Neurosciences, University of California San Diego School of Medicine, La Jolla 92093-0624, USA. · Neurology. · Pubmed #14663031 No free full text.

Abstract: OBJECTIVE: To determine the effect of idebenone on the rate of decline in Alzheimer's disease (AD). METHODS: A 1-year, multicenter, double-blind, placebo-controlled, randomized trial was conducted. Subjects were over age 50 with a diagnosis of probable AD and had Mini-Mental State Examination (MMSE) scores between 12 and 25. Subjects were treated with idebenone 120, 240, or 360 mg tid, each of which was compared with placebo. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive Subcomponent (ADAS-Cog) and a Clinical Global Impression of Change (CGIC). Secondary outcome measures included measurements of activities of daily living, the Behavioral Pathology in Alzheimer's Disease Rating Scale, and the MMSE. RESULTS: Five hundred thirty-six subjects were enrolled and randomized to the four groups. Except for a slight difference in age, there were no differences in patient characteristics at baseline. For the primary outcome measures, there were no significant overall differences between the treatment groups in the prespecified four-group design. In an exploratory two-group analysis comparing all three treated groups combined with placebo, drug-treated patients performed better on the ADAS-Cog in both the intent-to-treat (ITT) and completers analyses. There were no differences in the CGIC scores for the ITT or completers analyses in either the four-group or the two-group analyses. There were no overall differences on any of the secondary outcome measures in any of the analyses. CONCLUSION: Idebenone failed to slow cognitive decline in AD that was of sufficient magnitude to be clinically significant.

Griffith HR, Belue K, Sicola A, Krzywanski S, Zamrini E, Harrell L, Marson DC. · Department of Neurology and Alzheimer's Disease Research Center, University of Alabama at Birmingham, 35233-7340, USA. · Neurology. · Pubmed #12578926 No free full text.

Abstract: OBJECTIVES: To assess financial capacity in patients with mild cognitive impairment (MCI) using a standardized psychometric capacity measure. METHODS: Participants were 21 cognitively normal older controls, 21 patients with amnestic MCI, and 22 patients with mild AD. The Financial Capacity Instrument (FCI), a psychometric capacity measure consisting of 18 financial ability tests (tasks), 9 domains (activities), and 2 total scores, was administered to participants along with a battery of neuropsychological tests sensitive to dementia. Group differences were examined on the neuropsychological and financial capacity variables. RESULTS: Relative to controls, the MCI group demonstrated impairments in episodic memory, and also semantic knowledge, executive function, written arithmetic, and spatial attention. MCI participants demonstrated impairments in FCI domains of conceptual knowledge, cash transactions, bank statement management, and bill payment, and in overall financial capacity. The control and MCI groups performed significantly better than patients with AD on most financial capacity and cognitive measures. CONCLUSIONS: On direct assessment, patients with amnestic MCI as a group demonstrate impairments across a range of financial abilities. These impairments are mild and may only apply to a subset of patients with MCI. However, existing diagnostic criteria for MCI should be applied flexibly to include mild impairments in higher order activities of daily life such as financial capacity.

Marson DC, Martin RC, Wadley V, Griffith HR, Snyder S, Goode PS, Kinney FC, Nicholas AP, Steele T, Anderson B, Zamrini E, Raman R, Bartolucci A, Harrell LE. · Department of Neurology, SC 650, University of Alabama at Birmingham, Birmingham, AL 35294, USA. · J Am Geriatr Soc. · Pubmed #19453308 No free full text.

Abstract: OBJECTIVES: To investigate financial capacity in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) using a clinician interview approach. DESIGN: Cross-sectional. SETTING: Tertiary care medical center. PARTICIPANTS: Healthy older adults (n=75) and patients with amnestic MCI (n=58), mild AD (n=97), and moderate AD (n=31). MEASUREMENTS: The investigators and five study physicians developed a conceptually based, semistructured clinical interview for evaluating seven core financial domains and overall financial capacity (Semi-Structured Clinical Interview for Financial Capacity; SCIFC). For each participant, a physician made capacity judgments (capable, marginally capable, or incapable) for each financial domain and for overall capacity. RESULTS: Study physicians made more than 11,000 capacity judgments across the study sample (N=261). Very good interrater agreement was obtained for the SCIFC judgments. Increasing proportions of marginal and incapable judgment ratings were associated with increasing disease severity across the four study groups. For overall financial capacity, 95% of physician judgments for older controls were rated as capable, compared with 82% for patients with MCI, 26% for patients with mild AD, and 4% for patients with moderate AD. CONCLUSION: Physicians and other clinicians can reliably evaluate financial capacity in cognitively impaired older adults using a relatively brief, semistructured clinical interview. Patients with MCI have mild impairment in financial capacity, those with mild AD have emerging global impairment, and those with moderate AD have advanced global impairment. Patients with MCI and their families should proactively engage in financial and legal planning, given these patients' risk of developing AD and accelerated loss of financial abilities.

Li L, Cao D, Desmond R, Rahman A, Lah JJ, Levey AI, Zamrini E. · Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. · Dement Geriatr Cogn Disord. · Pubmed #18931498 links to  free full text

Abstract: BACKGROUND: Conflicting results have been reported on the association of plasma total homocysteine (tHcy) and cholesterol levels in Alzheimer disease (AD). The objective of this study was to determine the relationship between cognitive performance and plasma levels of tHcy and its biological determinants folate and vitamin B(12), and lipids in clinically diagnosed AD patients. METHODS: A cross-sectional database review was performed on two separate groups of patients (n = 191). Mini-Mental State Exam (MMSE) scores, plasma levels of tHcy, vitamin B(12), folate, cholesterol, and triglycerides were analyzed. RESULTS: The MMSE scores were inversely correlated with age, plasma levels of tHcy and LDL cholesterol. However, only the inverse relationship between MMSE scores and LDL cholesterol levels persisted after adjustment for age, sex, and status of statin treatment. Plasma tHcy levels increased significantly with age and were inversely related to vitamin B(12) and folate levels, which modified the relationship between MMSE scores and plasma tHcy levels. CONCLUSIONS: The plasma tHcy levels appeared to relate more to aging than to cognition. Cognitive performance was inversely associated with plasma LDL cholesterol levels in AD patients. Our findings provide further evidence that high LDL cholesterol levels may play a role in the pathogenesis of AD.

Martin R, Griffith HR, Belue K, Harrell L, Zamrini E, Anderson B, Bartolucci A, Marson D. · Department of Neurology and Alzheimer's Disease Research Center, University of Alabama at Birmingham, and VA Medical Center, Birmingham, AL 35294-0017, USA. · Am J Geriatr Psychiatry. · Pubmed #18263665 No free full text.

Abstract: OBJECTIVE: The objective of this study was to investigate change over time in financial abilities in patients with mild Alzheimer disease (AD). METHODS: The authors conducted a prospective 1-year longitudinal study at a large southern U.S. metropolitan-area medical school university. Participants included healthy older adults (N=63) and patients with mild AD (N=55). The authors conducted a standardized performance measure of financial capacity. Performance was assessed on 18 financial tasks, nine domains of financial activity, and overall financial capacity. Capacity outcomes classifications (capable, marginally capable, or incapable) for domains and overall performance were made using cut scores referenced to comparison group performance. RESULTS: At baseline, patients with mild AD performed significantly below healthy older adults on 16 of 18 tasks, on all nine domains, and on overall financial capacity. At one-year follow up, comparison group performance was stable on all variables. In contrast, patients with mild AD showed substantial declines in overall financial capacity, on eight of nine domains, and on 12 of 18 tasks. Similarly, the proportion of the mild AD group classified as marginally capable and incapable increased substantially over one year for the two overall scores and for five financial domains. CONCLUSIONS: Financial capacity is already substantially impaired in patients with mild AD at baseline and undergoes rapid additional decline over one year. Relative to the comparison group, overall financial capacity performance in the AD group declined 10%, from approximately 80% of the comparison group performance at baseline to 70% at follow up. Financial skills showed differential rates of decline on both simple and complex tasks. Of clinical and public policy interest was the declining judgment of patients with mild AD regarding simple fraud schemes. The study supports the importance of prompt financial supervision and planning for patients newly diagnosed with AD.

Salmon DP, Cummings JL, Jin S, Sano M, Sperling RA, Zamrini E, Petersen RC, Edland SD, Thal LJ, Ferris SH, Anonymous00337. · Department of Neurosciences, University of California, San Diego, La Jolla, California 92093-0948, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17135807 No free full text.

Abstract: The validity and reliability of clinic-based and telephone-based versions of a 4 word delayed recall test were evaluated in nondemented elderly individuals (n=644) participating in a simulated primary prevention clinical trial. There was no significant difference in the average scores achieved by participants tested in clinic (mean=3.40) or by telephone (mean=3.47) and the 2 groups had similar distributions of scores. Delayed recall scores were significantly, but weakly, correlated with scores on a rigorous verbal memory task, were lower in participants in Clinical Dementia Rating stage 0.5 than in those in Clinical Dementia Rating stage 0, and were lower in those with subjective memory complaints than in those without complaints. There was only fair correspondence between scores achieved at initial testing and 3 months later for both versions of the test. There were no differences in the average scores achieved by men or women, those older (age 80 to 93) or younger (age 75 to 79) than age 80, or those with white or nonwhite ethnicity. Participants with low education scored significantly lower than those with high education. Results suggest that clinic-based and telephone-based versions of the Four Word Delayed Recall Test are valid and reliable and can be used to screen for possible memory deficits in elderly individuals. However, the psychometric properties of the test are relatively weak and do not support the general use of the test for clinical and research purposes if the use of a more rigorous memory test with a wider range of possible scores is feasible.

Davis LL, Weaver M, Zamrini E, Stevens A, Kang DH, Parker CR. · School of Nursing, University of Alabama at Birmingham, 35294-1210, USA. · Biol Res Nurs. · Pubmed #15388906 No free full text.

Abstract: BACKGROUND: Thirty caregiving wives participated in a study of caregiving distress and negative mood (depressive symptoms) by making diary entries on stressful caregiving situations and collecting saliva samples 4 times a day. At the end of the 7-day study period, caregivers' salivary cortisol production was compared with their diary entries and correlated with pencil and paper self-report scores of caregiver distress and depressive symptoms. FINDINGS: Despite the inability to control a number of factors thought to confound cortisol production (exercise, smoking, alcohol ingestion, and prescription medications), there was a statistically significant difference between No Caregiving and Caregiving cortisol, F(1,739) = 7.67, P = 0.006, with cortisol production higher when caregiving events occurred. However, efforts to code specific types of caregiving situations (e.g., 1 = indirect care; 4 = AD problem behavior care) did not further differentiate cortisol production. Although caregivers' self-reports for the same 7-day period indicated they were depressed, pencil-and-paper measures of distress and negative affect were not significantly correlated with cortisol production. CONCLUSIONS AND RECOMMENDATIONS: The finding that this caregiving group was significantly stressed by caregiving, as evidenced by increased cortisol production during caregiving episodes, verifies the importance of further exploration of specific caregiving situations as contributory factors in caregiver health and well-being. In that saliva is a relatively economical and comparatively noninvasive biological data source for community-based stress studies, methodological limitations of the study are identified and 5 recommendations are made for future biological marker studies of caregiver distress in community-based settings.

Zamrini E, Parrish JA, Parsons D, Harrell LE. · Veteran's Administration Hospital, Alzheimer's Disease Center, Birmingham, AL, USA. · South Med J. · Pubmed #14746413 No free full text.

Abstract: BACKGROUND: Little is known about co-medical illnesses in black and white patients with probable Alzheimer's disease (AD). METHODS: To address this question, we used two methods. In the first (Group I), black and white probable AD patients were matched on age at presentation to the clinic, age of onset of AD, duration of illness, and Mini-Mental State Examination scores; then, a variety of co-medical illnesses were compared between blacks and whites. In Group II, whites were randomly matched to blacks on the variables listed above. RESULTS: In Group I, blacks were found to have a higher rate of hypertension than whites, whereas whites had a higher incidence of atrial fibrillation and cancer than blacks. In Group II, age at presentation to the clinic was found to be shorter for men than for women; duration of illness was shorter for black men than for white men, white women, and black women; and Mini-Mental State Examination scores were lower in blacks than whites. As in Group I, blacks were found to have a higher rate of hypertension, whereas whites had higher rates of atrial fibrillation, cancer, coronary artery disease, high cholesterol, and gastrointestinal disease. CONCLUSION: In both groups, black patients with probable AD had a higher rate of hypertension than white patients with probable AD, and whites had higher rates of atrial fibrillation and cancer. This finding suggests that these comorbid illnesses in black and white patients with probable AD is not due to a statistical Type II error, but rather to differences in these groups.

Zamrini E, McGwin G, Roseman JM. · Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, 35294, USA. · Neuroepidemiology. · Pubmed #14739574 No free full text.

Abstract: CONTEXT: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been associated with a decreased risk for Alzheimer's disease (AD). OBJECTIVE: To evaluate the association between statin use and AD adjusted for comorbid medical conditions. DESIGN: A nested case-control study. PATIENTS: Patients at the Veterans Affairs Medical Center in Birmingham, Ala., USA with a new diagnosis of AD (cases) between 1997 and 2001 (n = 309) and age-matched non-AD controls (n = 3,088). MAIN OUTCOME MEASURE: Odds ratio for association between AD and statin use. RESULTS: Statin users had a 39% lower risk of AD relative to nonstatin users (odds ratio 0.61, 95% confidence interval 0.42-0.87). This association appeared to be modified by the presence of certain chronic medical conditions (i.e., hypertension, ischemic heart disease and cerebrovascular disease) in that the reduced risk was observed among those with these diseases, whereas no association was observed among those without any of these conditions. CONCLUSIONS: In this study, following adjustment for confounding factors, a statistically significant inverse association between statin use and AD was observed. The results lend support to looking at AD outcomes in trials of statins to further evaluate their possible beneficial effects.