Alzheimer Disease: Lerner AJ

Hinze SW, Gaines AD, Lerner AJ, Whitehouse PJ. · No affiliation provided · Alzheimer Dis Assoc Disord. · Pubmed #10609665 No free full text.

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Lerner AJ, Strauss M, Sami SA. · Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. · Geriatrics. · Pubmed #17999565 No free full text.

Abstract: Apathy has been increasingly recognized as a neuropsychiatric symptom in many neurologic disorders. In this paper, we review the clinical features of apathy in Alzheimer's disease. We also review screening, the differential diagnosis including depression, medical illnesses, and mild cognitive impairment, and treating modalities and issues. It must also be recognized that apathy per se almost never occurs as an isolated syndrome, so it must be viewed in the context of an individual's entire behavioral and cognitive status.

Lerner AJ. · Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44120, USA. · J Clin Endocrinol Metab. · Pubmed #10522973 links to  free full text

This publication has no abstract.

Lerner AJ. · Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44120, USA. · J Clin Endocrinol Metab. · Pubmed #10372669 links to  free full text

Abstract: AD is a major public health problem, and demographic trends have led to its being called the epidemic of the century. Because of increased longevity and the special challenges of ERT, women are well placed to both be at risk for and the beneficiaries of advances in AD therapy. Overall increases in health consciousness may impact future AD risk, and it is encouraging that women frequently outnumber men in clinical trials of new therapeutic agents in AD. The risk of AD from environmental exposures in the overall life experiences of women is unclear. To the extent that education and work promote the development of brain areas such as the association cortex that are preferentially affected in AD, creating a neuronal reserve, advances in women's overall place in society may further help protect them from the ravages of AD.

Lerner AJ, Ogrocki PK, Thomas PJ. · Department of Neurology, University Hospitals Case Medical Center, Cleveland, OH 44120, USA. · Cogn Behav Neurol. · Pubmed #19372770 No free full text.

Abstract: BACKGROUND: Category fluency is impaired early in Alzheimer disease (AD). Graph theory is a technique to analyze complex relationships in networks. Features of interest in network analysis include the number of nodes and edges, and variables related to their interconnectedness. Other properties important in network analysis are "small world properties" and "scale-free" properties. The small world property (popularized as the so-called "6 degrees of separation") arises when the majority of connections are local, but a number of connections are to distant nodes. Scale-free networks are characterized by the presence of a few nodes with many connections, and many more nodes with fewer connections. OBJECTIVE: To determine if category fluency data can be analyzed using graph theory. To compare normal elderly, mild cognitive impairment (MCI) and AD network graphs, and characterize changes seen with increasing cognitive impairment. METHODS: Category fluency results ("animals" recorded over 60 s) from normals (n=38), MCI (n=33), and AD (n=40) completing uniform data set evaluations were converted to network graphs of all unique cooccurring neighbors, and compared for network variables. RESULTS: For Normal, MCI and AD, mean clustering coefficients were 0.21, 0.22, 0.30; characteristic path lengths were 3.27, 3.17, and 2.65; small world properties decreased with increasing cognitive impairment, and all graphs showed scale-free properties. Rank correlations of the 25 commonest items ranged from 0.75 to 0.83. Filtering of low-degree nodes in normal and MCI graphs resulted in properties similar to the AD network graph. CONCLUSIONS: Network graph analysis is a promising technique for analyzing changes in category fluency. Our technique results in nonrandom graphs consistent with well-characterized properties for these types of graphs.

McClendon MJ, Hernandez S, Smyth KA, Lerner AJ. · University Memory and Aging Center, Cleveland, OH, USA. · J Alzheimers Dis. · Pubmed #19276552 No free full text.

Abstract: The biological meaning of uncertain dementia ratings (CDR 0.5) and its treatment implications are unclear. Our study examines the frequency of anti-dementia medication use in individuals with CDR 0.5 and the cognitive, behavioral, and demographic factors associated with memantine and acetylcholinesterase inhibitor (AChEI) use. Subjects were drawn from the National Alzheimer Coordinating Center database, which collects data from 30 Alzheimer Disease Centers. There were 2,512 subjects with the following diagnoses: Normal, 11.8%; Mild cognitive impairment, 44.6%; Alzheimer's disease, 34.9%; and other dementias, 8.7%. Overall, 35% used AChEIs and 13% used memantine. AChEI and memantine use was greater in subjects who were referred by clinics and diagnosed with Alzheimer's disease. AChEI use was associated with being married, younger, male, and more educated while memantine use was associated with less severe apathy and other dementia diagnosis. Non-Hispanic whites were more likely to use AChEI and memantine than non-Hispanic blacks (OR = 2.2, 2.5). Hispanics were more likely to use AChEI than non-Hispanic blacks. It appears anti-dementia medication use in CDR 0.5 is frequent and represents evidence for extensive off label usage. Diagnosis, severity of impairment, and race, among other variables, affect the likelihood of AChEI and memantine use in this population.

Dwyer BE, Zacharski LR, Balestra DJ, Lerner AJ, Perry G, Zhu X, Smith MA. · Research Service, Department of Veterans Affairs Medical Center, White River Junction, VT 05009-0001, United States. · Med Hypotheses. · Pubmed #19195795 No free full text.

Abstract: This communication explores the temporal link between the age-associated increase in body iron stores and the age-related incidence of Alzheimer's disease (AD), the most prevalent cause of senile dementia. Body iron stores that increase with age could be pivotal to AD pathogenesis and progression. Increased stored iron is associated with common medical conditions such as diabetes and vascular disease that increase risk for development of AD. Increased stored iron could also promote oxidative stress/free radical damage in vulnerable neurons, a critical early change in AD. A ferrocentric model of AD described here forms the basis of a rational, easily testable experimental therapeutic approach for AD, which if successful, would be both widely applicable and inexpensive. Clinical studies have shown that calibrated phlebotomy is an effective way to reduce stored iron safely and predictably without causing anemia. We hypothesize that reducing stored iron by calibrated phlebotomy to avoid iron deficiency will improve cerebrovascular function, slow neurodegenerative change, and improve cognitive and behavioral functions in AD. The hypothesis is eminently testable as iron reduction therapy is useful for chronic diseases associated with iron excess such as nonalcoholic steatohepatitis (NASH), atherosclerosis, hereditary hemochromatosis and thalassemia. Testing this hypothesis could provide valuable insight into the causation of AD and suggest novel preventive and treatment strategies.

Lerner AJ, McClendon MJ, Sami SA, Ogrocki PK, Adams KB, Smyth KA. · Department of Neurology, University Hospitals Case Medical Center, Cleveland, OH, USA. · Alzheimer Dis Assoc Disord. · Pubmed #18525285 No free full text.

Abstract: Memantine is approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer disease (AD). We investigated the frequency and variables associated with its use in mild to moderate/severe AD as defined by criteria involving the Mini-Mental Status Examination (MMSE) and Clinical Dementia Rating (CDR) scale. Consecutive possible and probable AD patients seen at our research center from November 2003 to December 2006 were included. Individuals were classified as mild dementia either by CDR=1 or MMSE >or=15, using criteria derived in part from the pivotal trials of memantine used for its approval by the Food and Drug Administration. Of 117 patients, 37% of those with mild AD by MMSE criterion (total N=94), and 38% of those with mild AD by CDR criterion (total N=86) used memantine. Logistic regression was used to simultaneously estimate the odds ratios (ORs) of the likelihood of memantine usage associated with a set of predictor variables. Lower MMSE was associated with a greater likelihood of using memantine independent of CDR [ORMMSE=7.45, 95% confidence interval (CI)=1.50-37.05]; CDR was not significantly related to memantine use. Controlling both MMSE and CDR, Whites were more likely to use memantine than African Americans (OR=6.47, 95% CI=1.25-33.39). Patients who used other antidementia medications were more likely to use memantine than those who did not (OR=3.15, 95% CI=0.995-9.97). Eight other patient characteristics were not significant predictors. Use of memantine in mild AD was common. Patterns of memantine usage are complex and deserve further study in a larger sample because of their implications for medical system cost, equitable access to care, and risk of drug interactions.

Petot GJ, Vega U, Traore F, Fritsch T, Debanne SM, Friedland RP, Lerner AJ. · Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH, USA. · J Alzheimers Dis. · Pubmed #17851184 No free full text.

Abstract: The purpose of this study is to examine the relationship of height, Apolipoprotein E genotype (APOE) and Alzheimer's disease (AD). Using a case-control design, subjects were recruited from the research registry of the University Memory and Aging Center of Case Western Reserve University and University Hospitals of Cleveland. On entry to the study, height was measured on 239 probable or possible AD patients and 341 healthy controls living in northeast Ohio. Risk of AD was modeled as a function of quartile of height, APOE genotype, years of education and year of birth. Analyses were stratified by gender. For men, cases were more likely to be shorter when compared to controls (p=0.001). There was only a small difference in mean height between AD cases and controls among women (p=0.05). For men, height in the highest quartile [>179.7 cm (70.75 in)] had a 59% lower risk of developing AD that in the lowest quartile [< 169.5 cm (66.75 in)], controlling for year of birth, and education (p=0.03). For women without an APOE epsilon4 allele, increasing height was associated with lower risk for AD (OR=0.88; p=0.01) but no significant association was found for women with at least one epsilon4 allele (OR=1.03; p=0.56).

Lindstrom HA, Fritsch T, Petot G, Smyth KA, Chen CH, Debanne SM, Lerner AJ, Friedland RP. · University Memory and Aging Center, Case Western Reserve University, USA. · Brain Cogn. · Pubmed #15919546 No free full text.

Abstract: The relationship between leisure activities and development of cognitive impairment in aging has been the subject of recent research. We examined television viewing in association with risk of developing Alzheimer's disease (AD) in a case-control study. Given recent focus on the importance of intellectually stimulating activities as preventive measures against cognitive decline, it is important to examine the effects of less stimulating but common activities. Data are from 135 Alzheimer's disease cases and 331 healthy controls. Demographic characteristics and life history questionnaire responses on the number of hours spent on 26 leisure activities during middle-adulthood (ages 40-59) were analyzed. Logistic regression was used to examine the effects of middle-adulthood leisure activities on case vs. control status. Results indicate that for each additional daily hour of middle-adulthood television viewing the associated risk of AD development, controlling for year of birth, gender, income, and education, increased 1.3 times. Participation in intellectually stimulating activities and social activities reduced the associated risk of developing AD. Findings are consistent with the view that participation in non-intellectually stimulating activities is associated with increased risk of developing AD, and suggest television viewing may be a marker of reduced participation in intellectually stimulating activities.

Mizrahi EH, Bowirrat A, Jacobsen DW, Korczyn AD, Traore F, Petot GJ, Lerner AJ, Debanne SM, Adunsky A, Dibello PM, Friedland RP. · Department of Geriatric Medicine, Chaim Sheba Medical Center, Affiliated to the Tel-Aviv University, Sackler School of Medicine, Tel Hashomer, Israel. · J Neurol Sci. · Pubmed #15546600 No free full text.

Abstract: High plasma homocysteine (tHcy) is a risk factor for cardiovascular disease and stroke and Alzheimer's disease (AD). An inverse relationship has been reported between tHcy and plasma B12 and folate levels. Seventy-nine AD patients and 156 controls from three Arab villages in northern Israel participated. Plasma tHcy, B12 and folate levels were determined. Data were analyzed using univariate statistical tests and logistical regression with confounders. tHcy was significantly higher in AD patients (20.6+/-8.7 micromol/l) than in controls (16.4+/-6.5 micromol/l) (p=0.03) after correction for year of birth, gender and smoking status. Plasma B12 (322.9+/-136.0/350.5+/-175.3 pmol/l) and plasma folate (4.5+/-3.8/4.9+/-2.6 nmol/l) levels did not differ significantly between AD patients and controls. Subjects in the highest tHcy tertile or in the lowest B12 and folate tertiles did not have greater risk to develop AD. In this population residing in Arab villages in northern Israel, tHcy levels were significantly higher among AD patients than in controls. Plasma B12 and folate levels were lower among cases but were not significant. There was not a significant association between plasma tHcy, B12 and folate levels in controls or AD patients. High levels of tHcy may suggest the need for folate and vitamin B12 supplementation in this population.

Mizrahi EH, Jacobsen DW, Debanne SM, Traore F, Lerner AJ, Friedland RP, Petot GJ. · Department of Neurology, School of Medicine, Case Western Reserve University, USA. · J Nutr Health Aging. · Pubmed #12766793 No free full text.

Abstract: PURPOSE: To study the association between Alzheimer s disease (AD) and plasma total homocysteine (tHcy), dietary folate and vitamin B6. METHODS: 64 AD patients were matched by gender, age, and smoking status to 64 healthy controls. tHcy was determined using an automated immunoassay. Dietary patterns for three age periods (20-39, 40-59, and 60 + yrs) were assessed using a questionnaire adapted from the Block Health Habits and History Questionnaire. Respondents (cases by proxy) reported food frequencies, which were translated into estimated daily nutrient intakes. APOE genotype, cognitive performance (CDR, MMSE), blood lipids, and albumin were obtained for patients and controls. RESULTS: tHcy did not differ significantly between controls (11.5 +/- 3.7 mmol/L) and AD patients (12.3 +/- 4.3 mmol/L)(p=0.25). tHcy levels were not related in AD patients or controls to education, CDR, MMSE, blood lipids, albumin or ApoE genotype (p>0.15). There was a negative correlation between plasma tHcy and triglyceride levels in AD patients (p=0.023), but not in controls. AD patients consumed significantly less dietary vitamin B6 (p=0.05) and folate (p=0.001) after age 60 than controls. CONCLUSIONS: Although plasma tHcy levels were higher in cases than controls, this difference was not significant. tHcy levels were not related to cognitive status. Plasma tHcy was inversely correlated with triglyceride levels in AD patients but not in controls.

Petot GJ, Traore F, Debanne SM, Lerner AJ, Smyth KA, Friedland RP. · Department of Nutrition, The University Memory and Aging Center, Cleveland, OH 44120-1013, USA. · Metabolism. · Pubmed #12647263 No free full text.

Abstract: In a case control study of genetic and lifestyle risk factors for Alzheimer's disease (AD), we obtained recalled food consumption frequencies translated to nutrients and averaged over 2 age periods of adult life, 20 to 39 and 40 to 59 years. The proportion of controls with the apolipoprotein E epsilon4 (APOE epsilon4) genotype was significantly higher in the lowest tertile of fat consumption (36.3% of energy) compared with controls with epsilon4 in the highest tertile of fat intake (44.6% of energy). Healthy older persons with the epsilon4 allele who survived to be included in this study may be protected with lower dietary fat intake and other healthy behaviors. Diet-genotype interactions may have important influences on disorders of later life.

Petot GJ, Debanne SM, Riedel TM, Smyth KA, Koss E, Lerner AJ, Friedland RP. · Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44120, USA. · J Am Diet Assoc. · Pubmed #12067055 No free full text.

This publication has no abstract.

Fritsch T, McClendon MJ, Smyth KA, Lerner AJ, Chen CH, Petot GJ, Debanne SM, Soas A, Friedland RP. · University Alzheimer Center, Case Western Reserve University and University Hospitals of Cleveland, Ohio, USA. · Am J Alzheimers Dis Other Demen. · Pubmed #11765862 No free full text.

Abstract: The "reserve" hypothesis suggests that education should affect the clinical expression of Alzheimer's disease (AD), but results from studies examining this idea are not consistent. In a single study, we evaluated the effects of educational attainment on three aspects of the clinical expression of AD: age at symptom onset, rate of cognitive decline, and survival. Subjects were 258 persons with mild- or moderate-stage Alzheimer's, drawn from our AD Research Registry. With statistical adjustment for confounding variables present in a clinic-based design, we found that higher educational attainment was associated with slightly earlier reports of symptom onset and a slower rate of cognitive decline on the Mini-Mental State Exam (MMSE). Education did not affect time of survival until death. We conclude that, for subjects in our sample, education had modest effects on aspects of the clinical expression of AD. These effects were not fully consistent with predictions derived from the "reserve" hypothesis.

Debanne SM, Petot GJ, Li J, Koss E, Lerner AJ, Riedel TM, Rowland DY, Smyth KA, Friedland RP. · Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106-4965, USA. · J Am Geriatr Soc. · Pubmed #11527491 No free full text.

Abstract: OBJECTIVE: To examine the presence and extent of bias introduced by using surrogate respondents for healthy controls in a case-control study of Alzheimer's disease (AD). DESIGN: Comparative study of matched responses to questionnaire ascertaining lifestyle issues. SETTING: University Hospitals/Case Western Reserve University Alzheimer Center. PARTICIPANTS: Controls (n = 50) were identified through the Research Registry. Surrogates (n = 50) were their healthy relatives or friends. MEASUREMENTS: Answers in the areas of demographic and occupational history, smoking habits, medical history, dietary intake, and leisure and work activities were recorded. The analysis was based on methods for paired data. Continuous variables were analyzed, focusing on paired differences between self and surrogate responses. RESULTS: For occupations and exposures, over 80% of the surrogates agreed with the subjects on over 80% of the questions. On smoking history, over 90% of the surrogates agreed with the subjects on over 70% of the questions. On leisure and work activities, over 70% of the surrogates agreed with the subjects on over 50% of the questions. There was less agreement regarding medical history. For continuous variables, most paired t-tests of zero mean difference between self and surrogate responses resulted in nonrejection of this hypothesis. Computed mean differences were not always positive or always negative. CONCLUSION: We did not find systematic under- or overreporting by the surrogates of the controls. Therefore, if there are biases in the responses of surrogates of the AD cases in our case-control study, they would not be canceled out by using surrogates for the controls.

Friedland RP, Fritsch T, Smyth KA, Koss E, Lerner AJ, Chen CH, Petot GJ, Debanne SM. · Laboratory of Neurogeriatrics, Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. · Proc Natl Acad Sci U S A. · Pubmed #11248097 links to  free full text

Abstract: The development of Alzheimer's disease (AD) later in life may be reflective of environmental factors operating over the course of a lifetime. Educational and occupational attainments have been found to be protective against the development of the disease but participation in activities has received little attention. In a case-control study, we collected questionnaire data about 26 nonoccupational activities from ages 20 to 60. Participants included 193 people with probable or possible AD and 358 healthy control-group members. Activity patterns for intellectual, passive, and physical activities were classified by using an adaptation of a published scale in terms of "diversity" (total number of activities), "intensity" (hours per month), and "percentage intensity" (percentage of total activity hours devoted to each activity category). The control group was more active during midlife than the case group was for all three activity categories, even after controlling for age, gender, income adequacy, and education. The odds ratio for AD in those performing less than the mean value of activities was 3.85 (95% confidence interval: 2.65-5.58, P < 0.001). The increase in time devoted to intellectual activities from early adulthood (20-39) to middle adulthood (40-60) was associated with a significant decrease in the probability of membership in the case group. We conclude that diversity of activities and intensity of intellectual activities were reduced in patients with AD as compared with the control group. These findings may be because inactivity is a risk factor for the disease or because inactivity is a reflection of very early subclinical effects of the disease, or both.

Hemingway-Eltomey JM, Lerner AJ. · No affiliation provided · Am J Psychiatry. · Pubmed #10484967 links to  free full text

This publication has no abstract.