EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.

BACKGROUND: Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. PATIENTS AND METHODS: Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken. RESULTS: Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen. CONCLUSIONS: New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.

Impact of genetic variants of RFC1, DHFR and MTHFR in osteosarcoma patients treated with high-dose methotrexate.

Osteosarcoma patients are commonly treated with high doses of methotrexate (MTX). MTX is an analog of folate, which is essential for DNA synthesis. Genetic polymorphism at single nucleotide can be indicative to the prognostic outcome in patients. Germ-line variants in candidate genes, coding for enzymes active in the metabolism of MTX, were studied in 62 osteosarcoma patients. Patients harboring the GG genotype in reduced folate carrier 1 (RFC1) rs1051266 had significantly better survival in comparison with patients having the AA genotype (P=0.046). These patients also had a lower frequency of metastasis (15%, P=0.029). Also patients homozygous for the G allele of rs1053129 in the dihydrofolate reductase (DHFR) gene were more likely to have a metastasis (45%, P= 0.005), and the methylenetetetrahydrofolate reductase (MTHFR) 677C allele was associated with higher degree of liver toxicity (88%, P=0.007). The study suggests that germ-line variants in the MTX metabolic pathway are associated with survival and side effects in patients treated with MTX.

Self-efficacy for exercise, more than disease-related factors, is associated with objectively assessed exercise time and sedentary behaviour in rheumatoid arthritis.

OBJECTIVES: Until recently, reports of physical activity in rheumatoid arthritis (RA) were limited to self-report methods and/or leisure-time physical activity. Our objectives were to assess, determine correlates of, and compare to well-matched controls both exercise and sedentary time in a typical clinical cohort of RA. METHOD: Persons with established RA (seropositive or radiographic erosions; n = 41) without diabetes or cardiovascular disease underwent assessments of traditional and disease-specific correlates of physical activity and 7 days of triaxial accelerometry. Twenty-seven age, gender, and body mass index (BMI)-matched controls were assessed. RESULTS: For persons with RA, objectively measured median (25th-75th percentile) exercise time was 3 (1-11) min/day; only 10% (n = 4) of participants exercised for ≥ 30 min/day. Time spent in sedentary activities was 92% (89-95%). Exercise time was not related to pain but was inversely related to disease activity (r = -0.3, p < 0.05) and disability (r = -0.3, p < 0.05) and positively related to self-efficacy for endurance activity (r = 0.4, p < 0.05). Sedentary activity was related only to self-efficacy for endurance activity (r = -0.4, p < 0.05). When compared to matched controls, persons with RA exhibited poorer self-efficacy for physical activity but similar amounts of exercise and sedentary time. CONCLUSIONS: For persons with RA and without diabetes or cardiovascular disease, time spent in exercise was well below established guidelines and activity patterns were predominantly sedentary. For optimal care in RA, in addition to promoting exercise, clinicians should consider assessing sedentary behaviour and self-efficacy for exercise. Future interventions might determine whether increased self-efficacy can increase physical activity in RA.

Why do patients with radiation-induced sarcomas have a poor sarcoma-related survival?

BACKGROUND: This study aims to provide reasons for the poor sarcoma-related survival in patients with radiation-induced sarcoma (RIS). METHODS: We performed a case-control study comparing sarcoma-related survival of 98 patients with RIS to that of 239 sporadic high-grade malignant sarcomas. RESULTS: The cumulative sarcoma-related 5-year survival was 32% (95% confidence interval (CI): 22-42) for patients with RIS vs 51% (95% CI: 44-58) for controls (P<0.001). Female gender, central tumour site and incomplete surgical remission were significantly more frequent among RIS patients than in controls. In multivariate analysis incomplete surgical remission (hazard ratio (HR) 4.48, 95% CI: 3.08-6.52), metastases at presentation (HR 2.93, 95% CI: 1.95-4.41), microscopic tumour necrosis (HR 1.88, 95% CI: 1.27-2.78) and central tumour site (HR 1.71, 95% CI: 1.18-2.47) remained significant adverse prognostic factors, but not sarcoma category (RIS vs sporadic). CONCLUSION: The poor prognosis of RIS patients are not due to the previous radiotherapy per se, but related to the unfavourable factors - central tumour site, incomplete surgical remission, microscopic tumour necrosis and the presence of metastases, the two former factors overrepresented in RIS.

Anesthesia providers' perspectives on abortion provision: deductive findings from a qualitative study.

INTRODUCTION: A clinician's willingness to provide abortion care is complex. Anesthesia providers' experiences in providing anesthesia for abortion are not well studied. We aimed to explore anesthesia providers' perspectives on abortion provision. METHODS: We conducted semi-structured, qualitative interviews with currently practising anesthesia providers in the southeastern United States. Participants were recruited from scientific meetings of two regional anesthesiology organizations and via snowball sampling. A semi-structured interview guide included domains of standardized second trimester abortion cases and personal abortion attitudes. Data were coded and analyzed iteratively using both inductive and deductive approaches with MAXQDA software. Deductive results are presented. RESULTS: Fifteen participants completed interviews from February 2018 to February 2019, at which point thematic saturation occurred. Participants represented a range of provider type, years of experience, workplace setting, and prior abortion experience. Participants demonstrated varied personal abortion attitudes, with greater acceptability of maternal or fetal health indications than social or financial indications for abortion. Most participants were willing to provide anesthesia for abortion in specific clinical scenarios. CONCLUSIONS: Southeastern United States anesthesia providers hold a spectrum of personal views on abortion and are willing to provide anesthesia for second trimester abortion in specific clinical scenarios. Findings may inform future research or professional development activities, which are important efforts toward improving multidisciplinary abortion care.

Hypertension and incident dementia in community-dwelling elderly Yoruba Nigerians.

OBJECTIVES: To investigate the relationship between hypertension and dementia incidence in community-dwelling elderly Yoruba (aged 70 years and above) because of sparse information on dementia and its risk factors in developing countries. MATERIALS AND METHODS: Community-based, prospective study of consenting elderly Yoruba using two-stage design. Blood pressure was measured during the baseline evaluation at 2001 and hypertension was defined as BP ≥ 140/90 mmHg. Diagnosis of dementia and normal cognition was by consensus using standard criteria. Non-demented subjects from the 2001 evaluation wave were re-evaluated during the 2004 and 2007 waves for dementia. Logistic regression was used to examine the association of baseline hypertension and incident dementia, after adjusting for age, gender, education, and histories of stroke and smoking. P-values <0.05 were considered significant. RESULTS: During the 6-year follow-up, 120 individuals developed dementia, while 1633 remained non-demented. The frequency of hypertension in the demented group was significantly higher than in the non-demented (70.0% vs 60.2%, P = 0.034). Baseline hypertension was a significant risk factor for dementia (OR = 1.52; 95% CI 1.01-2.30). Higher systolic, diastolic or pulse pressure was associated with increased risk (P < 0.05). Participants with diastolic BP ≥ 90 mmHg were at a significantly greater risk than those with readings below 70 mmHg (OR = 1.65; 95% CI 1.01-2.69). CONCLUSIONS: Hypertension was associated with increased risk of dementia in elderly Yoruba and its appropriate treatment may lower the risk.

A brief dementia screener suitable for use by non-specialists in resource poor settings--the cross-cultural derivation and validation of the brief Community Screening Instrument for Dementia.

OBJECTIVE: Brief screening tools for dementia for use by non-specialists in primary care have yet to be validated in non-western settings where cultural factors and limited education may complicate the task. We aimed to derive a brief version of cognitive and informant scales from the Community Screening Instrument for Dementia (CSI-D) and to carry out initial assessments of their likely validity. METHODS: We applied Mokken analysis to CSI-D cognitive and informant scale data from 15 022 participants in representative population-based surveys in Latin America, India and China, to identify a subset of items from each that conformed optimally to item response theory scaling principles. The validity coefficients of the resulting brief scales (area under ROC curve, optimal cutpoint, sensitivity, specificity and Youden's index) were estimated from data collected in a previous cross-cultural validation of the full CSI-D. RESULTS: Seven cognitive items (Loevinger H coefficient 0.64) and six informant items (Loevinger H coefficient 0.69) were selected with excellent hierarchical scaling properties. For the brief cognitive scale, AUROC varied between 0.88 and 0.97, for the brief informant scale between 0.92 and 1.00, and for the combined algorithm between 0.94 and 1.00. Optimal cutpoints did not vary between regions. Youden's index for the combined algorithm varied between 0.78 and 1.00 by region. CONCLUSION: A brief version of the full CSI-D appears to share the favourable culture- and education-fair screening properties of the full assessment, despite considerable abbreviation. The feasibility and validity of the brief version still needs to be established in routine primary care.

Primary Ewing's Sarcoma of the Kidney in a 73-Year-Old Man.

Objective. Ewing's sarcoma of the kidney is rare and is usually found in young adults. We present here a single case study of Ewing's sarcoma found in an elderly man. Material and methods. A 73-year-old man underwent routine surgery for hydrocoele of the testis. He developed urinary obstruction symptoms, and radiological examinations revealed a tumour in the right kidney. Results. Microscopical, immunohistochemical, and molecular pathological analysis of the tumour was consistent with Ewing's sarcoma. FISH showed rearrangement of chromosomes 22q12 (EWSR1). The patient subsequently underwent nephrectomy followed by 6 adjuvant chemotherapy cycles. Follow-up after 7 months shows no recurrence. Conclusion. This case report presents not only the rare finding of Ewing's sarcoma in the kidney, but also the occurrence of this tumour entity in an elderly patient. Treatment options for the different types of renal tumours are vastly different and the need for a correct diagnosis is, therefore, vital.

Is diabetes associated with poorer self-efficacy and motivation for physical activity in older adults with arthritis?

OBJECTIVES: The primary aim was to explore whether arthritis is associated with poorer self-efficacy and motivation for, and participation in, two specific types of physical activity (PA): endurance training (ET) and strength training (ST). A further objective was to determine whether the added burden of diabetes contributes to a further reduction in these PA determinants and types. METHODS: Self-efficacy and motivation for exercise and minutes per week of ET and ST were measured in 347 older veterans enrolled in a home-based PA counselling intervention. Regression analyses were used to compare high versus low self-efficacy and motivation and PA minutes in persons without arthritis, with arthritis alone, and with arthritis plus diabetes. RESULTS: Persons with arthritis alone reported lower self-efficacy for ET and ST than those without arthritis [odds ratio (OR)ET 0.71, 95% confidence interval (CI) 0.39­1.20; ORST 0.69, 95% CI 0.39­1.20]. A further reduction in self-efficacy for these two types of PA was observed for those with both arthritis and diabetes (ORET 0.65, 95% CI 0.44­0.92; ORST 0.64, 95% CI 0.44­0.93; trend p < 0.001). There was no trend towards a reduction in motivation for PA in those with arthritis alone or with arthritis and diabetes. Persons with arthritis exhibited higher motivation for ET than those without arthritis (ORET 1.85, 95% CI 1.12­3.33). There were no significant differences between the three groups in minutes of ET (p = 0.93), but persons with arthritis plus diabetes reported significantly less ST compared to individuals with arthritis only (p = 0.03). CONCLUSIONS: Despite reduced self-efficacy for ET and ST and less ST in older persons with arthritis, motivation for both PA types remains high, even in the presence of diabetes.

Limb-sparing surgery preserves more function than amputation: a Scandinavian sarcoma group study of 118 patients.

We evaluated the long-term functional outcome in 118 patients treated for osteosarcoma or Ewing's sarcoma in the extremities a minimum of five years after treatment. We also examined if impaired function influenced their quality of life and ability to work. The function was evaluated according to the Musculoskeletal Tumor Society (MSTS) score and the Toronto Extremity Salvage Score (TESS). Quality of life was assessed by using the Short Form-36 (SF-36). The mean age at follow-up was 31 years (15 to 57) and the mean follow-up was for 13 years (6 to 22). A total of 67 patients (57%) initially had limb-sparing surgery, but four had a secondary amputation. The median MSTS score was 70% (17% to 100%) and the median TESS was 89% (43% to 100%). The amputees had a significantly lower MSTS score than those with limb-sparing surgery (p < 0.001), but there was no difference for the TESS. Tumour localisation above knee level resulted in significantly lower MSTS scores and TESS (p = 0.003 and p = 0.02, respectively). There were no significant differences in quality of life between amputees and those with limb-sparing surgery except in physical functioning. Of the patients 11% (13) did not work or study. In multivariate analysis, amputation, tumour location above the knee and having muscular pain were associated with low physical function. We conclude that most of the bone tumour survivors managed well after adjustment to their physical limitations. A total of 105 are able to work and have an overall good quality of life.

The synthetic hepatic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibit growth of MH1C1 rat hepatoma cells transplanted into Buffalo rats or athymic mice.

Repeated i.p. injections of the synthetic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibited the long-term growth of MH1C1 rat hepatoma cells by 50-70% in three in vivo models: metastatic colony growth in the lungs of young Buffalo rats; s.c. tumor growth in young Buffalo rats; and s.c. tumor growth in athymic mice. The amide free peptide pyroglutamylglutamylglycylserylaspartic acid which inhibited the tumor growth in all the models showed a curvilinear dose-response relationship with a maximal effect at 1000 pmol/animal in mice and at 100 pmol/animal in rats. The amidated peptide pyroglutamylglutamylglycylserylasparagine, which was only tested in the lung model, showed growth inhibition with 2, 20, or 200 pmol/animal, but 200 pmol/animal was most effective. We have recently reported that these peptides show cochromatography with hepatic growth inhibitory peptides, isolated from mouse liver.

The relationships between age, sex, and the incidence of dementia and Alzheimer disease: a meta-analysis.

BACKGROUND: Prevalence studies on dementia and Alzheimer disease (AD) have reported a positive association with age. However, the trend of the association in the oldest-old categories has been the subject of discussion. The relationship between sex and AD has been inconsistent with these studies. Prevalence rates are influenced by the survival and disease incidence. Incidence rates provide a better measure of disease risk. METHODS: English-language articles identified through a MEDLINE search on "incidence dementia" and "incidence Alzheimer's disease" were examined and references from identified articles were reviewed. Population-based studies using personal interviews, standard clinical diagnosis criteria (DSM-III for dementia, National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorder Association for AD) and reporting age-specific incidence rates were included in the meta-analysis. Data from the selected studies were extracted and verified. Mixed-effect models were used in the meta-analysis to accommodate the heterogeneity of the studies. RESULTS: Incident dementia and AD are associated with a significant quadratic age effect indicating that the increase in incidence rates slows down with the increase in age, although there is no sign of a decline in the incidence rates themselves. The odds ratios for women to develop incidence of dementia and AD relative to men are 1.18 (95% confidence interval, 0.95-1.46) and 1.56 (95% confidence interval, 1.16-2.10), respectively. CONCLUSIONS: The acceleration of incidence rates for AD and dementia slows down with the increase in age, although we find no evidence of a rate decline. Women are at higher risk of developing AD than men.

Caring for individuals with dementia: the Nigerian experience.

Recent epidemiological data, mainly from cross-cultural studies, have revealed that the burden of dementia and Alzheimer's disease (AD) the most common type, is significantly lower in developing than in the industrialized countries. Caring for individuals with dementia is a major consideration because most developing countries do not have the resources to provide comprehensive care in institutions. Home care that is practiced is ideal given the cultural scenario especially with the extended family support. Public policies on the care of the elderly however need to be well articulated and implemented. Hypertension was the most frequent medical co-morbidity of the demented subjects and about a third of subjects with AD were hypertensive, which may support vascular hypothesis in AD pathogenesis. The important behavioural disturbances experienced by caregivers and the associated stress levels were highlighted. The model used on the Indianapolis-Ibadan Dementia Study which involves periodic home visits, and empowerment of caregivers through regular meetings is envisaged to make caring for these individuals easier and adaptable in other African communities.

Psychiatric disorders in African American nursing home residents.

OBJECTIVE: High prevalence rates of psychiatric illness and high levels of behavioral disturbance have been reported in studies of nursing home residents; however, the populations evaluated have been predominantly Caucasian. The aims of the present study were to identify prevalence rates of psychiatric disorders and behavioral disturbances in a sample of African American nursing home residents. METHODS: The authors evaluated 106 African American nursing home residents, aged 65 and over, from a representative sample of nursing homes. The evaluation included informant interview with nursing home staff, cognitive assessment, and a psychiatric interview that included a physical and neurological examination. Consensus diagnoses were reached by using DSM-III-R criteria. RESULTS: Of the 106 subjects, 90% received at least one primary psychiatric diagnosis, and 71% had at least one behavioral problem; dementia was the most common psychiatric diagnosis (68%). Thirty -one percent of the patients were treated with neuroleptic medication; most of these patients received diagnoses of dementia or schizophrenia. Fifteen percent of the patients had been in physical restraints, which correlated with physical disability. CONCLUSIONS: The prevalence of psychiatric illness in this sample of African American nursing home residents is similar to that reported in previous studies with predominantly Caucasian populations. Behavioral disturbances, while commonly reported, were somewhat less frequent than reported in previous studies.

Prevalence of Alzheimer's disease and dementia in two communities: Nigerian Africans and African Americans.

OBJECTIVE: This article reports on a prevalence study of dementia and Alzheimer's disease among two groups of subjects with the same ethnic background but widely differing environments. METHOD: The study was conducted among residents aged 65 years and older in two communities: Yorubas (N = 2,494) living in Ibadan, Nigeria, and African Americans (N = 2,212 in the community and N = 106 in nursing homes) living in Indianapolis, Indiana. The study design consisted of a screening stage followed by a clinical assessment stage for selected subjects on the basis of their performance on the screening tests. RESULTS: The age-adjusted prevalence rates of dementia (2.29%) and Alzheimer's disease (1.41%) in the Ibadan sample were significantly lower than those in the Indianapolis sample, both in the community-dwelling subjects alone (4.82% and 3.69%, respectively) and in the combined nursing home and community samples (8.24% and 6.24%, respectively). The prevalence rates of dementia and Alzheimer's disease increased consistently with advancing age in both study groups. CONCLUSIONS: To the authors' knowledge, this is the first study, using the same research method at the two sites, to report significant differences in rates of dementia and Alzheimer's disease in two different communities with similar ethnic origins.

Relationship of age, education, and occupation with dementia among a community-based sample of African Americans.

OBJECTIVE: To explore the relationship between age, education, and occupation with dementia among African Americans. DESIGN: Community-based survey to identify subjects with and without evidence of cognitive impairment and subsequent diagnostic evaluation of a stratified sample of these subjects using formal diagnostic criteria for dementia. SETTING: Urban neighborhoods in Indianapolis, Ind. SUBJECTS: A random sample of 2212 African Americans aged 65 years and older residing in 29 contiguous census tracts. MEASUREMENTS: Subjects's scores on the Community Screening Instrument for Dementia (CSI-D), formal diagnostic clinical assessments for dementia, years of education, rural residence, primary occupation, self-reported disease, and alcohol and smoking history. Caseness was defined by four separate criteria: (1) cognitive impairment as defined by the subject's performance on the CSI-D cognitive scale; (2) cognitive impairment as defined by the total CSI-D score that included a relative's assessment of the subject's functional abilities; (3) dementia as defined by explicit diagnostic criteria; and (4) possible or probable Alzheimer's disease as defined by explicit diagnostic criteria. RESULTS: The mean age was 74 years (age range, 65 to 100 years), 65% of subjects were women, the mean education was 9.6 years (age range, 0 to 16 years), 98% of the subjects were literate, and 32% reported living in a rural area until age 19 years. Service, domestic, and production occupations accounted for 55.2% of the subjects' primary occupations with a mean of 25.8 years (range, 1 to 75 years) in the primary occupation. Years of education, rural residence to age 60 years, and primary occupation were highly correlated. Caseness defined by any of the four criteria was associated with functional impairment, but the frequency of impairment increased with increasing diagnostic specificity. Age, education, and rural residence to age 60 years were significantly independently associated with caseness for cognitive impairment, dementia, and Alzheimer's type dementia. White-collar occupation was independently associated only with caseness for cognitive impairment. History of stroke was associated with caseness for cognitive impairment and dementia but not Alzheimer's disease, while history of smoking was negatively correlated with Alzheimer's disease. CONCLUSIONS: Education was independently associated with cognitive impairment and dementia among a representative community-based sample of African Americans and the association remains significant across a variety of sensitivity analyses designed to control for measurement and confounding biases. The potential protective role of education against the development of dementia among African Americans deserves further evaluation.

Low education and childhood rural residence: risk for Alzheimer's disease in African Americans.

OBJECTIVE: To examine the relationship between level of education and childhood rural residence as possible risk factors for AD in African Americans in Indianapolis. BACKGROUND: Low level of education has been a risk factor for AD in some studies, but childhood rural residence has not been addressed in most of these studies. METHODS: A two-stage community-based prevalence study of AD was conducted in a random sample of 2,212 African Americans > or =65 years of age. A subsample of clinically assessed normal individuals (180) and individuals diagnosed with AD (43) were compared on the variables of rural/urban residence in childhood and low (< or =6 years) or high (> or =7 years) education. A logistic regression model was used with interaction between rural residence and low education to estimate odds ratios for the two risk factors combined, adjusting for age and gender. RESULTS: Odds ratios for AD: 6.5 (95% CI: 2.6 to 16.7) low education/rural residence; 0.5 (95% CI: 0.1 to 2.9) low education/urban residence; 1.5 (95% CI: 0.4 to 5.2) high education/rural residence, comparing with the group of high education/urban residence. CONCLUSION: Childhood rural residence, combined with < or =6 years of school, was associated with an increased risk of AD in this sample. It is possible that low education by itself is not a major risk factor for AD, but, rather, is a marker for other accompanying deleterious socioeconomic or environmental influences in childhood.

Cognitive decline and education in mild dementia.

Recent studies suggested that education may modify the clinical expression of dementia and Alzheimer's disease through its association with a brain reserve capacity. We studied whether education would be related to degree of cognitive decline in mild dementia. Equations to estimate premorbid cognitive ability were derived from a representative normative sample of 83 community-dwelling African Americans using age, education, and gender as independent variables and Word List Learning (WLL) and Animal Fluency (AF) scores from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery as dependent variables. These equations were applied to a second sample of 131 African Americans (22 with dementia, 109 healthy) who completed CERAD test batteries as part of an epidemiologic study of dementia in the community. Differences between obtained and estimated premorbid WLL and AF test scores were calculated and then analyzed in a 2 (Education) x 2 (Diagnosis) ANOVA. A significant interaction association between Education and Diagnosis on WLL scores and a borderline significant interaction on AF scores showed that the high-education demented group had a greater cognitive decline from estimated premorbid levels than the low-education demented group. Thus, at comparable levels of clinical dementia severity, greater cognitive decline occurred in highly educated patients than in low-educated patients.

Serum cholesterol, APOE genotype, and the risk of Alzheimer's disease: a population-based study of African Americans.

A significant interaction among total serum cholesterol (TC), APOE genotype, and AD risk was found in a population-based study of elderly African Americans. Increasing TC was associated with increased AD risk in the group with no epsilon4 alleles, whereas TC was not associated with increased AD risk in the group with one or more epsilon4 alleles. Further study of the relationship between cholesterol and APOE genotype is needed to confirm this association, but the results suggest that cholesterol may be a potentially modifiable environmental risk factor for AD.

Prevalence of cognitive impairment: data from the Indianapolis Study of Health and Aging.

BACKGROUND: The epidemiology and natural history of cognitive impairment that is not dementia is important to the understanding of normal aging and dementia. OBJECTIVE: To determine the prevalence and outcome of cognitive impairment that is not dementia in an elderly African American population. METHOD: A two-phase, longitudinal study of aging and dementia. A total of 2212 community-dwelling African American residents of Indianapolis, IN, aged 65 and older were screened, and a subset (n = 351) received full clinical assessment and diagnosis. Subsets of the clinically assessed were seen again for clinical assessment and rediagnosis at 18 and 48 months. Weighted logistic regression was used to generate age-specific prevalence estimates. RESULTS: The overall rate of cognitive impairment among community-dwelling elderly was 23.4%. Age-specific rates indicate increasing prevalence with increasing age: 19.2% for ages 65 to 74 years, 27.6% for ages 75 to 84 years, and 38.0% for ages 85+ years. The most frequent cause of cognitive impairment was medically unexplained memory loss with a community prevalence of 12.5%, followed by medical illness-associated cognitive impairment (4.0% prevalence), stroke (3.6% prevalence), and alcohol abuse (1.5% prevalence). At 18-month follow-up, 26% (17/66) of the subjects had become demented. CONCLUSIONS: Cognitive impairment short of dementia affects nearly one in four community-dwelling elders and is a major risk factor for later development of dementia.