Robust and conventional neuropsychological norms: Diagnosis and prediction of age-related cognitive decline.

The aim of the study was to compare the performance of Robust and Conventional neuropsychological norms in predicting clinical decline among healthy adults and in mild cognitive impairment (MCI). The authors developed Robust baseline cross sectional and longitudinal change norms from 113 healthy participants retaining a normal diagnosis for at least 4 years. Baseline Conventional norms were separately created for 256 similar healthy participants without follow-up. Conventional and Robust norms were tested in an independent cohort of longitudinally studied healthy (n=223), MCI (n=136), and Alzheimer's disease (AD, n=162) participants; 84 healthy participants declined to MCI or AD (NL→DEC), and 44 MCI declined to AD (MCI→AD). Compared to Conventional norms, baseline Robust norms correctly identified a higher proportion of NL→DEC with impairment in delayed memory and attention-language domains. Both norms predicted decline from MCI→AD. Change norms for delayed memory and attention-language significantly incremented baseline classification accuracies. These findings indicate that Robust norms improve identification of healthy individuals who will decline and may be useful for selecting at-risk participants for research studies and early interventions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Longitudinal deficits to attention, executive, and working memory in subtypes of mild cognitive impairment.

Objective: Mild cognitive impairment (MCI) has emerged as a classification for a prodromal phase of cognitive decline that may precede the emergence of Alzheimer's disease (AD). Recent research suggests that attention, executive, and working memory deficits may appear much earlier in the progression of AD than traditionally conceptualized, and may be more consistently associated with the later development of AD than memory processing deficits. The present study longitudinally tracked attention, executive and working memory functions in subtypes of MCI. Method: In a longitudinal study, 52 amnestic MCI (a-MCI), 29 nonamnestic MCI (na-MCI), and 25 age- and education-matched controls undertook neuropsychological assessment of visual and verbal memory, attentional processing, executive functioning, working memory capacity, and semantic language at 10 month intervals. Results: Analysis by repeated measures ANOVA indicate that the a-MCI and na-MCI groups displayed a decline in simple sustained attention (ηp2 = .054) with a significant decline on a task of divided attention (ηp2 = .053) being evident in the a-MCI group. Stable deficits were found on other measures of attention, working memory and executive function in the a-MCI and na-MCI groups. The a-MCI group displayed stable impairments to visual and verbal memory. Conclusions: The results indicate that a-MCI and na-MCI display a stable pattern of deficits to attention, working memory, and executive function. The decline in simple sustained attention in a-MCI and n-MCI groups and to divided attention in a-MCI may be early indicators of possible transition to dementia from MCI. However, further research is required to determine this. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Task switching performance reveals heterogeneity amongst patients with mild cognitive impairment.

Objective: To assess executive function in patients with mild cognitive impairment (MCI) and to determine whether task switching ability is associated with transition to Alzheimer's disease. Methods: Twenty-seven MCI patients and 19 older controls were tested using a cued letter-digit classification switching task. Sixteen patients could perform the task (MCI-able), 6 could not (MCI-unable), and 5 were able only with cognitive support (MCI-cue). Demographic, neuropsychological, event-related potential (ERP), MRI, and genetic data were also collected. Results: The four groups did not differ on age, gender, and APO E4 frequency. Compared to the controls, the MCI-unable group had significantly poorer performance on the Trail Making task (η2 = .430), lower education (η2 = .234), and smaller cortical volume (η2 = .245). Most MCI patients exhibited task-switching deficits but to vastly different degrees and with varying outcomes. The combined pattern of neuropsychological and task switching performance indicates that the MCI-able patients displayed memory retrieval difficulties (F(2,39) = 3.6, p = .036, MSE = 1.44), generally preserved task switching abilities, and had a high probability of remaining dementia-free at follow-up. The MCI-cue patients had increased mixing costs, F(2,39) = 11.0, p     

Association between apolipoprotein E epsilon4 and the rate of cognitive decline in community-dwelling elderly individuals with and without dementia

OBJECTIVE: To determine whether the apolipoprotein E epsilon4 allele (apoE epsilon4) is associated with cognitive decline in individuals with and without dementia, we conducted a 4-year longitudinal study of subjects with a range of cognitive function. SETTING: At baseline, respondents (n=511) were randomly selected according to age and Mini-Mental State Examination score from a community-based study of dementia among noninstitutionalized persons aged 65 to 84 years. Respondents were examined at baseline and followed up in 3 annual visits. At baseline, subjects were classified as having normal cognitive function, minimal dementia, or dementia, according to criteria from the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) and the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Of the 511 respondents at baseline, 405 who were examined at least 2 times are included in this analysis. MAIN OUTCOME MEASURES: Cognitive decline was determined by a slope estimating yearly change in score on the neuropsychological test, the CAMCOG (the cognitive section of the CAMDEX), and its sub-scales of memory and nonmemory functions. RESULTS: Among the subjects who had normal cognitive function at baseline, apoE epsilon4 carriers showed a significantly greater decline (P<.001) in score on the CAMCOG compared with noncarriers. Differences in decline on the memory and nonmemory subtests were also significant (P<.001). Rates of cognitive decline were not related to apoE epsilon4 status in the groups with minimal dementia and dementia. CONCLUSIONS: In our community-based sample, apoE epsilon4 was associated with the rate of cognitive decline prior to the clinically symptomatic phase of dementia. Knowing the apoE epsilon4 status of those already symptomatic for dementia may not improve knowledge about a patient's prognosis.     

Racial differences in rate of CD4 decline in HIV-1-infected homosexual men

OBJECTIVE: To determine whether racial differences exist in the rate of CD4 lymphocyte decline in HIV-1-infected homosexual men. DESIGN: Prospective cohort study. STUDY POPULATION: Non-Hispanic white (n = 321) and black (n = 102) HIV-1-seropositive homosexual and bisexual men were recruited from the Baltimore/Washington, DC metropolitan areas between 1984-1985 and 1987-1990, and evaluated semiannually. MAIN MEASUREMENTS: Changes in CD4 lymphocyte count and CD4 percentage over time were analysed using linear regression methods for the 271 white and 69 black participants who had at least four semiannual CD4 lymphocyte measurements. RESULTS: Rate of decline in CD4 lymphocyte count over 6 months was much slower among black than white seroprevalent men at all levels of baseline CD4 count (baseline 201-400 x 10(6)/l: + 0.24 versus -17.7 x 10(6)/l; 401-600 x 10(6)/l: -11.3 versus -23.9 x 10(6)/l; 601-800 x 10(6)/l: -15.1 versus -35.2 x 10(6)/l; > 800 x 10(6)/l: -4.3 versus -42.7 x 10(6)/l for black versus white, respectively), although this was only statistically significant for the lowest and highest strata of baseline CD4 count. These racial differences persisted after adjustment for recruitment period (1984-1985 or 1987-1990), follow-up duration, age and zidovudine therapy or Pneumocystis carinii pneumonia prophylaxis. Similar findings were observed among the 70 white and 11 black seroconverters. Black participants were also less likely than a subgroup of white participants matched on baseline CD4 lymphocyte count to be HIV-1 p24 antigen-positive. However, after acid dissociation of samples initially p24 antigen-negative, there were no significant differences in the prevalence of p24 antigenemia at enrollment or after 1 year of follow-up. CONCLUSIONS: This analysis suggests a more gradual decline in CD4 lymphocyte count among black than white Americans. The clinical significance of and reasons for this are unclear, but the lower prevalence of p24 antigenemia due to immune complexing among black Americans suggests that racial differences in the immune response to HIV may exist. Additional studies are needed to validate these findings in a larger cohort of non-whites, and to assess their relationship with other measures of cell-mediated immune function.     

Apolipoprotein E phenotype and cognitive decline in a prospective study of elderly community women

OBJECTIVE: To determine whether apolipoprotein E (Apo E) phenotype is associated with cognitive decline in community-dwelling nondemented elderly women. DESIGN: Prospective cohort study. SETTING: A university-affiliated clinic near Pittsburgh, Pa. PATIENTS: A total of 1750 nondemented community-dwelling women, aged 65 years and older, who were enrolled in the Study of Osteoporotic Fractures. MAIN OUTCOME MEASURES: The women completed a baseline interview and performed 3 cognitive tests: the modified Mini-Mental State Examination, Trials B, and Digit Symbol. Serum samples were obtained for Apo E typing. Baseline cognitive scores and repeated scores approximately 6 years after study enrollment were compared in women with and without Apo E epsilon 4. Cognitive decline, defined as the worst 10th percentile change scores, was assessed for each test and by phenotype group. RESULTS: After adjustment for age, education, presence of severe tremor, and depression, baseline scores did not differ by Apo E epsilon 4 status except for lower scores on Trails B in the homozygous epsilon 4 group (mean score, 159.7 compared with 127.7 for the heterozygous epsilon 4 group and 125.4 for the no epsilon 4 group; P = .01). However, repeated test performance on follow-up examination was worse on all tests in those women with 1 or more epsilon 4. Reduction on the modified Mini-Mental State Examination was 0% for no epsilon 4 allele, 1.9% for 1 epsilon 4 allele, and 3.7% for 2 epsilon 4 alleles (P < .001); reduction on Digit Symbol was 6.2% for no epsilon 4 allele, 9.0% for 1 epsilon 4 allele, and 17.5% for 2 epsilon 4 alleles (P = .04); and reduction on Trials B was 5.9% for no epsilon 4 allele, 25.0% for 1 epsilon 4 allele, and 10.9% for 2 epsilon 4 alleles (P = .002). Women with at least 1 epsilon 4 had an odds ratio of 1.6 (95% confidence interval, 1.1-2.3) of having cognitive decline during the study period. CONCLUSION: Apolipoprotein E epsilon 4 is associated with cognitive decline in community-dwelling nondemented women.     

Cognitive profiles of mild cognitive impairment with and without vascular disease.

This study examined whether the cognitive profile of subjects with mild cognitive impairment (MCI) with vascular disease differs from that of MCI subjects with no vascular disease. Consecutive MCI subjects with vascular disease (n=60) and matched MCI subjects with no vascular disease (n=60) were included in the study and were compared with healthy control subjects (n=60). The neuropsychological assessment comprised tests of speed and attention, episodic memory, visuospatial function, language, and executive function. Control subjects performed significantly better than did both MCI groups on the neuropsychological battery. MCI subjects with no vascular disease performed better overall than did MCI subjects with vascular disease, most clearly on tests of speed and attention, visuospatial function, and executive function. MCI subjects with and without vascular disease exhibited differences, both in terms of overall performance and of cognitive profiles. These differences can be largely explained by deficits in speed and attention and in executive function of the MCI subjects with vascular disease. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Heterogeneity of cognitive trajectories in diverse older persons.

This study examined trajectories of cognitive change in psychometrically matched measures of episodic memory, semantic memory, and executive function in an ethnically, demographically, and cognitively diverse sample of older persons. Individual rates of change showed considerable heterogeneity in each domain. Baseline clinical diagnosis predicted differential change in semantic memory and executive function, dementia > mild cognitive impairment (MCI) > normal, but average decline in verbal episodic memory was similar across all 3 diagnostic groups. There was substantial overlap of distributions of cognitive change across baseline diagnostic groups for all 3 measures. Cognitive change was strongly related to change in clinical diagnosis. Rapid and similar change was present for all 3 cognitive measures in patients with dementia and in those with normal cognition and those with MCI who progressed clinically. In cognitively normal patients, verbal episodic memory change was greater than change in the other two domains. Global status, measured by the Clinical Dementia Rating scale (Morris, 1993), predicted change in semantic memory and executive function, whereas APOE genotype predicted change in verbal episodic memory, and age had no effect on rates of change in any domain independent of global status and APOE. Results show important limitations in using cross-sectional diagnosis to predict prognosis and suggest that research to identify robust predictors of cognitive change across the full spectrum from normal to dementia is needed for better early identification of diseases that cause progressive decline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Semantic inhibition impairment in mild cognitive impairment: A distinctive feature of upcoming cognitive decline?

This study aimed to measure semantic inhibitory capacities in persons with a diagnosis of Alzheimer’s disease (AD) or mild cognitive impairment (MCI), in healthy older and younger adults. This was done by relying on a computerized adaptation of the Hayling task, designed to diminish the likelihood of using alternative noninhibitory strategies. Participants with both AD and MCI showed impaired performance on the inhibition condition. Participants with AD showed both poorer score and an increased number of errors, whereas persons with MCI obtained lower score. There was also an effect of normal aging in the inhibition condition when considering reaction time only. In participants with MCI and AD, there was a significant correlation between lexico-semantic capacities and performance on the automatic condition. Follow-up analysis revealed that participants with MCI who experienced a subsequent significant cognitive decline had impaired performance in the inhibition condition at the time of the experiment, while participants with MCI who remained stable did not. Overall, results indicate that semantic inhibition of a prepotent response is impaired in participants with MCI and may have predictive value regarding future decline, supporting its prognostic role in the early identification of dementia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selectivity of executive function deficits in mild cognitive impairment.

Impairment in executive cognition (EC) is now recognized as relatively common among older persons with mild cognitive impairment (MCI) and may be predictive of the development of dementia. However, both MCI and executive functioning are broad and heterogeneous constructs. The present study sought to determine whether impairments in specific domains of EC are associated with specific subtypes of MCI. MCI patients (n = 124) were divided into 4 subgroups (amnestic vs. nonamnestic, and single- vs. multiple-domain) on the basis of their performance of widely used neuropsychological screening tests. These patients and 68 normal older persons were administered 18 clinical and experimental tests of executive function. Principal components analysis suggested 2 highly reliable EC components, planning/problem solving and working memory, and a less reliable 3rd component, judgment. Planning/problem solving and working memory, but not judgment, were impaired among the MCI patients. This was true even among those with “pure amnestic” MCI, the least impaired group overall. Multiple-domain MCI patients had more severe impairments in planning/problem solving and working memory than single-domain patients, leading to the supposition that they, not pure amnestic MCIs, are at highest risk of imminent dementia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of time perspective in smoking cessation amongst older English adults.

Objective: To study the longitudinal relationship between time perspective and smoking cessation over 4 years of follow-up among a cohort of older English adults and to determine whether the predictive utility of time perspective in smoking cessation. Design: Analysis of data from core members of the English Longitudinal Survey of Ageing who took part in face-to-face interviews in 2002, 2004, and 2006 (n = 7,174). Main Outcome Measures: Time perspective was measured using a question on time period for financial planning. Smoking at baseline and quitting over follow-up was determined through self-report. Results: At baseline, planning for longer periods was associated with lower odds of being a smoker, after controlling for age, gender, and education. Among those who were smokers at baseline, planning for longer periods at baseline was associated with increased odds of quitting over 4 years, after controlling for age, gender, and education. Conclusion: Including help to become more future orientated in smoking cessation interventions may increase their effectiveness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Durable effects of implementation intentions: Reduced rates of confirmed pregnancy at 2 years.

Objective: To assess the long-term impact of implementation intention formation in reducing consultations for emergency contraception and pregnancy testing among teenage women. Design: Teenage women visiting a family planning clinic were randomly assigned to implementation intention versus control conditions. Main outcome measures: Objective measures of consultation outcomes were obtained from clinic records at 2-year follow-up (N = 227). Results: Rates of consultation for emergency contraception and pregnancy testing in the implementation intentions condition were 19% and 33% lower, respectively, compared to the rates observed in the control condition. Pregnancy rates were 43% lower. Intervention participants who consulted for emergency contraception and pregnancy testing at baseline were more than twice as likely to change to consulting for contraceptive supplies over the follow-up period compared to equivalent control participants (19% vs. 9%). Conclusion: The impact of implementation intention formation on reducing pregnancy risk among teenagers is durable over 2 years. Implementation intentions were successful in changing behavior among precisely those participants who were at greatest risk of becoming pregnant. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Working memory in mild cognitive impairment and Alzheimer's disease: Contribution of forgetting and predictive value of complex span tasks.

Objective: This study examines working memory (WM) in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Method: Performances on sentence span and operation span were measured in individuals meeting criteria for MCI (n = 20) and AD (n = 16) as well as in healthy older adults (n = 20). In addition, the effect of retention interval was assessed by manipulating the length of first and last items of trials (long-short vs. short-long), as forgetting might contribute to impaired performance in AD and MCI. Results: Results show a group effect (p     

Use of IQ-Adjusted Norms to Predict Progressive Cognitive Decline in Highly Intelligent Older Individuals.

Identifying high-functioning older individuals in preclinical phases of Alzheimer's disease (AD) may require more sensitive methods than the standard approach. The authors explored the utility of adjusting for premorbid intelligence to predict progressive cognitive decline or Mild Cognitive Impairment (MCI) in 42 highly intelligent older individuals. When scores were adjusted for baseline IQ, 9 participants had executive impairments, 11 had memory impairments, and 22 scored in the normal range. None were impaired according to standard age norms. Three and a half years later, 9 participants with IQ-adjusted memory impairment declined in naming, visuospatial functioning, and memory; 6 convened to MCI. Three participants with normal memory declined. Implications for using IQ-adjusted norms to predict preclinical AD are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Longitudinal MRI and cognitive change in healthy elderly.

Cross-sectional studies of normal aging indicate an association between memory and hippocampal volume, and between executive functioning and subcortical-frontal circuits. Much less is known, however, about the relationship between longitudinal MRI changes and cognitive decline. The authors hypothesized that longitudinal change in memory would be best predicted by change in hippocampal volumes, whereas change in executive functioning would be best predicted by cortical atrophy and progression of MRI markers of cerebrovascular disease. For this study, 50 healthy elderly subjects underwent structural MRI and cognitive testing at baseline and again at follow-up, with a mean follow-up interval of 45 months. Volumetric MRI measures were hippocampus, cortical gray matter, white matter signal hyperintensity (WMSH), and lacunae. Neuropsychological measures were psychometrically robust composite scores of episodic memory (MEM) and executive functioning (EXEC). Hierarchical multiple regression indicated that a decrease in hippocampus was associated with a decline in MEM, whereas decreased cortical gray matter and increased WMSH were independently associated with a decline in EXEC. Results suggest that in normal aging, cognitive functioning declines as cortical gray matter and hippocampus decrease, and WMSH increases. The association between WMSH and EXEC further highlights the cognitive sequealae associated with cerebrovascular disease in normal elderly. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Working memory and control of attention in persons with Alzheimer's disease and mild cognitive impairment.

The goal of the present study was to assess 3 attentional control processes--divided attention, manipulation capacities, and inhibition--in persons with mild cognitive impairment (MCI) and with mild Alzheimer's disease (AD). Manipulation capacities were tested by comparing immediate serial recall with alphabetical-order recall of words. Divided attention was tested with the Brown-Peterson procedure, in which participants divide their attention between simple addition tasks and consonant trigrams over delays. Inhibition was tested with the Hayling procedure, in which participants complete sentences with words irrelevant to their context. Persons with AD showed severe impairment on the 3 attentional control components. Persons with MCI exhibited impaired performance on the Brown-Peterson procedure but normal performance on the other 2 tasks. With AD and MCI participants, there was a negative correlation between general cognitive deficits and impairment on attentional control tasks, indicating that attentional control deficits increase in the MCI/AD continuum. When separating MCI with and without significant subsequent decline, those with subsequent decline showed impaired performance on both the Brown-Peterson procedure and manipulation task. These data suggest that control of attention tasks can track AD at a preclinical stage and that impairment increases gradually during the preclinical phase of AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serum estrogen levels, cognitive performance, and risk of cognitive decline in older community women

OBJECTIVE: To determine the association between serum estrogen levels, cognitive performance, and risk of cognitive decline in older women. DESIGN: Prospective cohort study with an average follow-up of 5 years. SETTING: Clinical centers in Baltimore, MD, Minneapolis, MN, Portland, OR, and the Monongahela Valley in Pennsylvania. PARTICIPANTS: 532 women aged 65 years or older who were the controls from two nested case-control studies in the ongoing Study of Osteoporotic Fractures. OUTCOME MEASURES: Three cognitive tests--a modified Mini-Mental Status Exam, Digit Symbol, and Trails B--were administered at study initiation and were then repeated approximately 5 years later. Estrone and estradiol levels were determined by radioimmunoassay at two laboratories from baseline stored serum. RESULTS: The characteristics of the women in the four serum estrogen quartiles did not differ except that body weight and change in weight since age 50 increased directly with higher quartile of serum estrogen (P < .001, for both estrone and estradiol). Initial cognitive performance on all three tests did not differ consistently by quartile of estradiol or by the estradiol to estrone ratio. Women in the higher estrone quartiles had 15% lower (worse) scores on Digit Symbol compared with the lower quartiles (P=.004) but there was no difference by quartile on the modified MMSE or on Trails B. Cognitive function test scores declined over the 5 years of follow-up. There was no difference in amount of change by quartile of estradiol, but women in the higher estrone quartiles had greater reduction of scores on Trails B compared with those in the lower quartiles (P=.012), even after adjusting for age, education, depression, stroke history, weight, and change in weight since age 50. The age-adjusted odds of cognitive decline (defined as tenth percentile of women with the largest decline in cognitive performance) did not vary across quartile of estrone or estradiol. CONCLUSIONS: Endogenous estrogens are not associated consistently with cognitive performance or risk of cognitive decline on a selected battery of cognitive tests in older community-dwelling women. Worse performance on two cognitive tests among women with higher estrone levels was surprising and warrants further investigation.     

Norms for change in episodic memory as a prerequisite for the diagnosis of mild cognitive impairment (MCI).

The new diagnostic criteria for mild cognitive impairment (MCI) from the International Working Group on Mild Cognitive Impairment (Winblad et al., 2004, p. 243) list “evidence of decline over time in objective cognitive tasks” as one diagnostic sign, implying the repeated neuropsychological testing. This study aimed to compare different assessment methods of longitudinal change based on the performances of 366 cognitively healthy participants (237 men, 129 women) examined with a German version of the California Verbal Learning Test (Delis, Kramer, Kaplan, & Ober, 1987) at baseline and 2 years later. Age, education, gender, and baseline performance were taken into account. Results revealed marked practice effects after 2 years. Normal ranges for change that controls for practice effects and regression to the mean proved to be superior to other reliable change indexes. This new method allows for more valid interpretation of change in neuropsychological functioning and thus diagnosis of MCI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Quantification of alterations in structure and function of elastin in the arterial media

The effect of environmental tobacco smoke (ETS) exposure on adults with asthma has not been well characterized. In a prospective cohort study of 451 nonsmoking adults with asthma, we evaluated the impact of ETS exposure on asthma severity, health status, and health care utilization over 18 mo. There were 129 subjects (29%; 95% CI, 25-33%) who reported regular ETS exposure, falling into three categories: exposure at baseline but none at follow-up (n = 43, 10%), no baseline exposure and new exposure at follow-up (n = 56, 12%), and exposure at both baseline and follow-up (n = 30, 7%). In cross-sectional analyses, subjects with baseline ETS exposure had greater severity-of-asthma scores (score difference, 1.7; 95% CI, 0. 2-3.1), worse asthma-specific quality of life scores (score difference, 3.5; 95% CI, 0.03-7.0), and worse scores on the Medical Outcomes Study SF-36 physical component summary (score difference, 3. 0; 95% CI, 0-6.0) than unexposed subjects. They also had greater odds of emergency department visits (odds ratio [OR] = 2.1; 95% CI, 1.2-3.5), urgent physician visits (OR = 1.9; 95% CI, 1.1-3.3), and hospitalizations (OR = 1.9; 95% CI, 1.02-3.6). In longitudinal follow-up, subjects reporting ETS cessation showed improvement in severity-of-asthma scores (score reduction, -3.2; 95% CI, -4.4 to -2. 0) and physical component summary scores (score increase, 5.3; 95% CI, 2.6-8.1). Environmental tobacco smoke cessation decreased the odds of emergency department visits (OR = 0.4; 95% CI, 0.2-0.97) and hospitalizations (OR = 0.2; 95% CI, 0.04-0.97) after adjustment for covariates. Environmental tobacco smoke initiation was associated with greater asthma severity only in subjects with high-level (>= 3 h/wk) exposure (score increase, 1.4; 95% CI, 0.03-2.7). In conclusion, self-reported ETS exposure is associated with greater asthma severity, worse health status, and increased health care utilization in adults with asthma.     

Apolipoprotein e4 allele and cognitive decline in elderly men

OBJECTIVES: To determine whether polymorphism of apolipoprotein E--notably, the e4 allele--predicts cognitive deterioration in the general population. DESIGN: Population based cohort investigated in 1990 and in 1993. SETTING: Zutphen, the Netherlands. SUBJECTS: Representative cohort of 538 Dutch men aged 70-89 at baseline. MAIN OUTCOME MEASURES: Cognitive function assessed by mini mental state examination, change in cognitive function and incidence of impaired cognitive function at three years. RESULTS: The baseline prevalence of impaired cognitive function (mini mental state examination score < or = 25) was higher among carriers of the e4 allele compared with men without the allele (41.0% (55) v 31.1% (122) P = 0.03), and this result was still valid after adjustment for age, occupation, smoking, alcohol use, and cardiovascular diseases. The decline in cognitive function at three years was largest in men homozygous for e4 (-2.4 points), intermediate in those heterozygous for e4 (-0.7 points), and lowest in men without e4 (-0.1 points), and it was independent of other risk factors (P = 0.02). The risk of developing impaired cognitive function during follow up was significantly increased in allele carriers compared with non-carriers (27.6% (16/58) v 15.5% (32/207)). The adjusted odds ratio was 2.87 (95% confidence interval 1.29 to 6.42). Twenty two per cent of the risk of developing impaired cognitive function in this population may be attributable to the e4 allele. CONCLUSIONS: The apolipoprotein e4 allele predisposes to cognitive decline in a general population of elderly men.