Centrally Acting ACE Inhibitor Use and Physical Performance in Older Adults.

BACKGROUND: There is conflicting evidence regarding the role of angiotensin-converting enzyme inhibitors and physical function. While some studies show improvements in muscle strength and physical function, others show no significant difference or decreased performance. This ambiguity could be due to differential effects of angiotensin-converting enzyme inhibitor subtypes which can be categorized as centrally or peripherally-acting based upon their ability to cross the blood-brain barrier. OBJECTIVE: The objective of this study is to compare physical performance measures among angiotensin-converting enzyme inhibitor subtype users. METHODS: Design: Cross-sectional Setting: Ambulatory Participants: Performed in 364 participants in the Health and Retirement Study cohort who were ≥ 65 years (median age (IQR) 74.00 (69-80) years. MEASUREMENTS: Average difference in hand grip (kg), gait speed(m/s) and peak expiratory flow (L/min). RESULTS: Compared to participants on a peripherally-acting angiotensin-converting enzyme inhibitor (113 (31%)), those on a centrally-acting agent (251(69%)) had stronger grip strength 28.9 ±1.0 vs 26.3±1.0, p=.011 and higher peak expiratory flow rates 316.8±130.4 vs. 280.0±118.5, p= .011 in unadjusted analysis. After multiple adjustments the difference in PEF remained statistically significant (Estimate(CI) 26.5, 95% CI 2.24, 50.5, p = 0.032). CONCLUSION: Our results suggest that in older adults the use of centrally-acting angiotensin-converting enzyme inhibitors compared to a peripherally acting angiotensin-converting enzyme inhibitors was associated with better lung function in older individuals.

World Trade Center exposure, post-traumatic stress disorder, and subjective cognitive concerns in a cohort of rescue/recovery workers.

OBJECTIVE: To determine whether World Trade Center (WTC)-exposure intensity and post-traumatic stress disorder (PTSD) are associated with subjective cognitive change in rescue/recovery workers. METHOD: The population included 7875 rescue/recovery workers who completed a subjective cognition measure, the Cognitive Function Instrument (CFI), between 3/1/2018 and 2/28/2019 during routine monitoring, indicating whether they had experienced cognitive and functional difficulties in the past year. Higher scores indicated greater self-perceived cognitive change. Probable PTSD, depression, and alcohol abuse were evaluated by validated mental health screeners. Logistic regression assessed the associations of WTC exposure and current PTSD with top-quartile (≥2) CFI score, and of early post-9/11 PTSD with top-quartile CFI in a subpopulation (N = 6440). Models included demographics, smoking, depression, and alcohol abuse as covariates. RESULTS: Mean age at CFI completion was 56.7 ± 7.7 (range: 36-81). Participants with high-intensity WTC exposure had an increased likelihood of top-quartile CFI score (odds ratio[OR] vs. low exposure: 1.32, 95%CI: 1.07-1.64), controlling for covariates. Current and early PTSD were both associated with top-quartile CFI (OR: 3.25, 95%CI: 2.53-4.19 and OR: 1.56, 95%CI: 1.26-1.93) respectively. CONCLUSIONS: High-intensity WTC exposure was associated with self-reported cognitive change 17 years later in rescue/recovery workers, as was PTSD. Highly WTC-exposed subgroups may benefit from additional cognitive evaluation and monitoring of cognition over time.

Cognitive activities delay onset of memory decline in persons who develop dementia.

BACKGROUND: Persons destined to develop dementia experience an accelerated rate of decline in cognitive ability, particularly in memory. Early life education and participation in cognitively stimulating leisure activities later in life are 2 factors thought to reflect cognitive reserve, which may delay the onset of the memory decline in the preclinical stages of dementia. METHODS: We followed 488 initially cognitively intact community residing individuals with epidemiologic, clinical, and cognitive assessments every 12 to 18 months in the Bronx Aging Study. We assessed the influence of self-reported participation in cognitively stimulating leisure activities on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. RESULTS: Each additional self-reported day of cognitive activity at baseline delayed the onset of accelerated memory decline by 0.18 years. Higher baseline levels of cognitive activity were associated with more rapid memory decline after that onset. Inclusion of education did not significantly add to the fit of the model beyond the effect of cognitive activities. CONCLUSIONS: Our findings show that late life cognitive activities influence cognitive reserve independently of education. The effect of early life education on cognitive reserve may be mediated by cognitive activity later in life. Alternatively, early life education may be a determinant of cognitive reserve, and individuals with more education may choose to participate in cognitive activities without influencing reserve. Future studies should examine the efficacy of increasing participation in cognitive activities to prevent or delay dementia.

Education delays accelerated decline on a memory test in persons who develop dementia.

OBJECTIVE: To test the cognitive reserve hypothesis by examining the effect of education on memory decline during the preclinical course of dementia. BACKGROUND: Low education is a well known risk factor for Alzheimer disease (AD). Persons destined to develop AD experience an accelerated rate of decline in cognitive ability, particularly in memory. The cognitive reserve hypothesis predicts that persons with greater education begin to experience acceleration in cognitive decline closer to the time of diagnosis than persons with lower reserve, but that their rate of decline is more rapid after the time of acceleration due to increased disease burden. METHODS: We studied the influence of education on rates of memory decline as measured by the Buschke Selective Reminding Test in 117 participants with incident dementia in the Bronx Aging Study. Subjects had detailed cognitive assessments at entry and at annual follow-up visits. We estimated the time at which the rate of decline begins to accelerate (the change point), and the pre- and post-acceleration rates of decline, from the longitudinal data using a change point model. RESULTS: Each additional year of formal education delayed the time of accelerated decline on the Buschke Selective Reminding Test by 0.21 years. Post-acceleration, the rate of memory decline was increased by 0.10 points per year for each year of additional formal education. CONCLUSIONS: As predicted by the cognitive reserve hypothesis, higher education delays the onset of accelerated cognitive decline; once it begins it is more rapid in persons with more education.

Identifying seizure clusters in patients with epilepsy.

Clinicians often encounter patients whose neurologic attacks appear to cluster. In a daily diary study, the authors explored whether clustering is a true phenomenon in epilepsy and can be identified in the clinical setting. Nearly half the subjects experienced at least one episode of three or more seizures in 24 hours; 20% also met a statistical clustering criterion. Utilizing the clinical definition of clustering should identify all seizure clusterers, and false positives can be determined with diary data.

Dementia incidence may increase more slowly after age 90: results from the Bronx Aging Study.

BACKGROUND: Dementia incidence increases dramatically from age 65 to age 85, with many studies reporting a doubling every 5 years. The incidence beyond age 85 is not established. OBJECTIVE: To estimate the incidence of dementia as a function of age, with a particular focus on persons aged 85 and over. METHODS: The Bronx Aging Study began in 1980 with 488 healthy, nondemented community-dwelling individuals, age 75 to 85. Persons in the study received clinical examinations and cognitive testing approximately every 12 months until death or loss to follow-up. The diagnosis of dementia was made using Diagnostic and Statistical Manual of Mental Disorders-III-R at diagnostic case conferences. Dementia incidence rates were calculated for 5-year age bands using person-time of follow-up as the denominator. RESULTS: The relative incidence rate ratios of dementia for age 80 to 84 vs 75 to 79 was 2.32 (95% CI 1.23 to 4.37), the relative rate for age 85 to 89 vs 80 to 84 was 1.89 (95% CI 1.26 to 2.83), the relative rate for age 90 to 94 vs 85 to 89 was 1.49 (95% CI 0.86 to 2.58), while the relative rate for age 95 to 99 vs 90 to 94 was 1.31 (95% CI 0.38 to 4.46). Similar results were seen for men and women considered separately. Had the rate of increase from age 75 to 89 continued into the 90s, the study would have had 73% power to detect a significant difference between the rates for age 90 to 94 and 85 to 89 given the amount of observed follow-up time. CONCLUSIONS: Whereas dementia incidence continues to increase beyond age 85, the rate of increase appears to slow relative to that of 65- to 85-year-olds. These results suggest that dementia in the oldest old might be related not to the aging process itself but with age-associated risk factors.

Low blood pressure and the risk of dementia in very old individuals.

BACKGROUND: The role of blood pressure (BP) as a risk factor for dementia is complex and may be age dependent. In very old individuals, low BP might increase risk for dementia, perhaps by reducing cerebral perfusion pressure. METHODS: The association between BP and dementia was examined in the Bronx Aging Study, a prospective study of 488 community-dwelling elderly individuals over age 75, dementia-free at baseline (1980 to 1983) and followed at 12- to 18-month intervals. Subjects with baseline BP and with at least one follow-up visit were included (n = 406). Incident dementia was diagnosed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders (3rd rev. ed.). RESULTS: Over 21 years (median 6.7 years), 122 subjects developed dementia (65 Alzheimer's disease [AD], 28 vascular dementia, 29 other dementias). Relative risk of dementia increased for each 10-mm Hg decrement in diastolic (hazard ratio [HR] 1.20, 95% CI 1.03 to 1.40) and mean arterial (HR 1.16, 95% CI 1.02 to 1.32) pressure, adjusted for age, sex, and education. Low diastolic BP significantly influenced risk of developing AD but not vascular dementia. Upon examination of groups defined by BP, mildly to moderately raised systolic BP (140 to 179 mm Hg) was associated with reduced risk for AD (HR vs normal systolic BP group 0.55, 95% CI 0.32 to 0.96), whereas low diastolic BP (

Respiratory syncytial virus infections in previously healthy working adults.

During 1975-1995, a total of 2960 healthy adults, 18-60 years of age, were prospectively evaluated for respiratory virus infections. Of these subjects, 211 (7%) acquired respiratory syncytial virus (RSV) infection. The infections were symptomatic in 84% of subjects, involved only the upper respiratory tract in 74%, and included lower respiratory tract symptoms in 26%. Overall, 40% of the subjects were febrile. Lower respiratory tract signs developed in 26%. RSV illnesses were more prolonged than non-RSV respiratory illnesses. Compared with influenza, RSV infections were less frequently associated with fever and headache, but were associated significantly more often with nasal congestion, ear and sinus involvement, and productive cough. Absence from work during the acute phase of the illness resulted from 38% of RSV infections and 66% of influenza cases. The mean duration of RSV illness (9.5 days), however, was significantly longer than that of influenza (6.8 days). The occurrence of annual epidemics of RSV, the virus' potential to reinfect all age groups, and the morbidity associated with these reinfections suggest that RSV infections in working adults may result in appreciable costs for medical visits and absence from work.

Diagnosing pediatric asthma: validating the Easy Breathing Survey.

OBJECTIVE: To determine the sensitivity, specificity, and predictive value of a simple, self-administered questionnaire for the diagnosis of asthma in children. STUDY DESIGN: A questionnaire specifically designed to assist primary care providers in making a diagnosis of asthma in children was developed and administered in 4 different primary care and subspecialty clinics, validated, and then used as part of an asthma management program called Easy Breathing. Asthma diagnoses were made according to recommended National Asthma Expert Panel Guidelines. RESULTS: Four questions on the survey were shown to be sensitive and specific for asthma. The sensitivity was greater for all levels (mild, moderate, and severe) of persistent asthma than for mild, intermittent asthma. A positive response to any 1 of the 4 questions was over 94% sensitive for asthma; a negative response to all 4 questions was 55% specific for ruling out asthma. CONCLUSIONS: Patient responses to 4 specific respiratory symptom questions can assist primary care providers in diagnosing asthma in children. Primary care providers serving pediatric populations at high risk for asthma should consider asking patients or their parents these 4 questions regarding asthma symptoms on a regular basis.

Validation of dual x-ray absorptiometry for body-composition assessment of rats exposed to dietary stressors.

Evidence of the validity and accuracy of dual x-ray absorptiometry (DXA) to measure soft-tissue composition of laboratory rats with altered body composition associated with nutritional perturbations is lacking. We compared DXA determinations made in prone and supine positions with measurements of chemical composition of 49 male, weanling Sprague-Dawley rats that were fed the basal AIN-93 growth diet, were fed the basal diet modified to contain 30% fat, were fasted for 2 d, were limit fed 6 g of the basal diet daily for 1 wk, or were treated with furosemide (10 mg/kg intraperitoneally 2 h before DXA). DXA produced similar estimates of body mass and soft-tissue composition in the prone and supine positions. DXA estimates of body composition were significantly correlated with reference composition values (R(2) = 0.371-0.999). DXA discriminated treatment effects on body mass, fat-free and bone-free mass, fat mass, and body fatness; it significantly underestimated body mass (1% to 2%) and fat-free and bone-free mass (3%) and significantly overestimated fat mass and body fatness (3% to 25%). The greatest errors occurred in treatment groups in which body mass was diminished and body hydration was decreased. These findings suggest that DXA can determine small changes in fat-free, bone-free mass in response to obesity and weight loss. Errors in DXA determination of fat mass and body fatness associated with extra corporeal fluid and dehydration indicate the need for revision of calculation algorithms for soft-tissue determination.

Estimation of bivariate measurements having different change points, with application to cognitive ageing.

Longitudinal studies of ageing make repeated observations of multiple measurements on each subject. Change point models are often used to model longitudinal data. We demonstrate the use of Bayesian and profile likelihood methods to simultaneously estimate different change points in the longitudinal course of two different measurements of cognitive function in subjects in the Bronx Aging Study who developed Alzheimer's disease (AD). Analyses show that accelerated memory decline, as measured by Buschke Selective Reminding, begins between seven and eight years before diagnosis of AD, while decline in performance on speeded tasks as measured by WAIS Performance IQ begins slightly more than two years before diagnosis, significantly after the decline in memory.

Nosocomial respiratory syncytial virus infections: the "Cold War" has not ended.

Respiratory syncytial virus (RSV) is a major nosocomial hazard on pediatric wards during its annual outbreaks. It produces significant morbidity in young children and is most severe in those with underlying conditions, especially cardiopulmonary and immunosuppressive diseases. In older patients, RSV may exacerbate an underlying condition or pulmonary and cardiac manifestations. On transplant units, of RSV may be occult and is associated with high mortality rates. The manifestations of nosocomial RSV infections may be atypical, especially in neonates and immunosuppressed patients, resulting in delayed or missed diagnosis and adding appreciably to the costs of hospitalization. RSV is primarily spread by close contact with infectious secretions, either by large-particle aerosols or by fomites and subsequent self-inoculation, and medical staff are often instrumental in its transmission. Thus, integral to any infection control program is the education of personnel about the modes of transmission, the manifestations, and the importance of RSV nosocomial infections. Hand washing is probably the most important infection control procedure. The choice of barrier controls should be decided by individual institutions depending on the patients, the type of ward, and the benefit relative to cost.

Circulation patterns of group A and B human respiratory syncytial virus genotypes in 5 communities in North America.

Human respiratory syncytial virus (HRSV) is a major cause of serious lower respiratory tract illness in infants, young children, and the elderly. To characterize the circulation patterns of HRSV strains, nucleotide sequencing of the C-terminal region of the G protein gene was performed on 34-53 isolates obtained from 5 communities during 1 epidemic year, representing distinct geographical locations in North America. Phylogenetic analysis revealed that 5-7 HRSV genotypes, including 1 or 2 predominant strains, circulated in each community. The patterns of genotypes were distinct between communities, and less diversity was seen between strains of the same genotype within than between communities. These findings are consistent with HRSV outbreaks' being community based in nature, although transmission of viruses between communities may occur. Several strains are probably introduced or circulate endemically in communities each year, and local factors-possibly immunity induced by previous years' strains-determine which strains predominate during an HRSV season.

A change point model for estimating the onset of cognitive decline in preclinical Alzheimer's disease.

Dementia is characterized by accelerated cognitive decline before and after diagnosis as compared to normal ageing. Determining the time at which that rate of decline begins to accelerate in persons who will develop dementia is important both in describing the natural history of the disease process and in identifying the optimal time window for which treatments might be useful. We model that time at which the rate of decline begins to accelerate in persons who develop dementia relative to those who do not by using a change point in a mixed linear model. A profile likelihood method is proposed to draw inferences about the change point. The method is applied to data from the Bronx Ageing Study, a cohort study of 488 initially non-demented community-dwelling elderly individuals who have been examined at approximately 12-month intervals over 15 years. Cognitive function was measured using the Buschke Selective Reminding test, a memory test with high reliability and known discriminative validity for detecting dementia. We found that the rate of cognitive decline as measured by this test in this cohort increases on average 5.1 years before the diagnosis of dementia.

White matter abnormalities in mobility-impaired older persons.

OBJECTIVE: To investigate the relationship between white matter abnormalities and impairment of gait and balance in older persons. METHODS: Quantitative MRI was used to evaluate the brain tissue compartments of 28 older individuals separated into normal and impaired groups on the basis of mobility performance testing using the Short Physical Performance Battery. In addition, individuals were tested on six indices of gait and balance. For imaging data, segmentation of intracranial volume into four tissue classes was performed using template-driven segmentation, in which signal-intensity-based statistical tissue classification is refined using a digital brain atlas as anatomic template. RESULTS: Both decreased white matter volume, which was age-related, and increased white matter signal abnormalities, which were not age-related, were observed in the mobility-impaired group compared with the control subjects. The average volume of white matter signal abnormalities for impaired individuals was nearly double that of control subjects. CONCLUSIONS: This cross-sectional study suggests that decreased white matter volume is age-related, whereas increased white matter signal abnormalities are most likely to occur as a result of disease. Both of these changes are independently associated with impaired mobility in older persons and therefore likely to be additive factors of motor disability.

Respiratory syncytial virus and premature infants born at 32 weeks' gestation or earlier: hospitalization and economic implications of prophylaxis.

OBJECTIVES: To assess the risk of hospitalization associated with respiratory syncytial virus (RSV) and to estimate the economic impact of RSV prophylaxis with either RSV immune globulin (RSV-Ig) or RSV monoclonal antibody (palivizumab) on a cohort of preterm infants born at 32 weeks' gestation or earlier. DESIGN: Historical cohort study. SETTING: A 12-county neonatal network served by the regional center in Rochester, NY. PARTICIPANTS: One thousand twenty-nine infants born at 32 weeks' gestation or earlier followed up until 1 year of corrected age. MAIN OUTCOME MEASURES: Rate of hospitalization with an RSV-associated illness; cost per hospitalization prevented resulting from either form of RSV prophylaxis. RESULTS: The probability of hospitalization with an RSV-associated illness for infants born at 32 weeks' gestation or earlier was estimated at 11.2%. The incidence of RSV hospitalization increased with decreasing gestational age (13.9% vs 4.4% for infants born at < or =26 weeks' gestation vs those born at 30-32 weeks' gestation). Infants requiring respiratory support at 36 weeks of postconceptual age (PCA) or older had a higher hospitalization rate (16.8% vs 6.2%), longer hospital stays, and higher hospital charges than infants requiring respiratory support at less than 36 weeks of PCA. For infants requiring respiratory support at less than 36 weeks of PCA, the incidence of RSV hospitalization still increased with decreasing gestational age (10.2% vs 4.3% for infants < or =26 weeks' gestation vs those 30-32 weeks' gestation). Analysis indicated that both forms of RSV prophylaxis would increase the net cost of care for all groups. Palivizumab was more cost-effective than RSV-Ig for preventing RSV hospitalization among infants who required respiratory support at less than 36 weeks of PCA, especially those born at 26 weeks' gestation or earlier. Overall, RSV-Ig was more cost-effective than palivizumab for infants requiring respiratory support at 36 weeks of PCA or older. CONCLUSIONS: This analysis suggests that available forms of RSV prophylaxis would increase the net cost of care not only for the entire cohort but for each of the subgroups studied. However, the RSV hospitalization rate and the cost-effectiveness of prophylaxis varied markedly by subgroup.

Timing of vaccinations in premature infants.

Preterm infants have immunological immaturities that may impact on vaccine responses. Larger premature infants mount immune responses to vaccines that are similar to those of full term infants, but very premature infants (<30 weeks' gestation at birth) have specific defects in vaccine responsiveness. The immunogenicity of diphtheria, tetanus and pertussis antigens is similar in full term and premature infants. Poliovirus vaccines, however, do not always stimulate adequate antibody responses in premature infants. The immunogenicity of Haemophilus influenzae type b conjugate vaccines varies widely in studies of premature infants, and may be affected both by choice of conjugate protein and by the infant's overall health. Hepatitis B vaccine given at birth appears poorly immunogenic in infants with birthweights <1750g, with delay in the administration of the first dose yielding improved immunogenicity. Sick premature infants may suffer increased episodes of apnoea following vaccine administration. Persistence of immunity, the quality of the immune response, and evaluation of the specific tolerability and immunogenicity of new vaccines in premature infants are topics needing further research. Although it is generally true that recommendations for vaccination of term infants are applicable to premature infants, it is not always specifically true. Optimal care of preterm infants requires attention to the exceptions to this generalisation.

Detection of human herpesvirus 6 by reverse transcription-PCR.

The role of human herpesvirus 6 (HHV-6) in disease beyond primary infection remains unclear. We have developed and validated a new reverse transcription-PCR (RT-PCR) assay for HHV-6 that can determine the presence of HHV-6 in clinical specimens and differentiate between latent and replicating virus. Peripheral blood mononuclear cells from 109 children were evaluated for HHV-6 by RT-PCR, DNA PCR, and viral culture. Of these samples, 106 were suitable for analysis. A total of 20 samples were positive for HHV-6 by culture and DNA PCR, of which 19 were positive by RT-PCR (sensitivity, 95%). All 28 samples from children that were negative by viral culture, but positive by DNA PCR, were negative for viral transcripts by our RT-PCR assay. One positive RT-PCR result was observed in 56 samples that were negative by tissue culture and DNA PCR. This indicates a low rate of false-positive results (1.2%) and a specificity of 98.8%. This RT-PCR assay can reliably differentiate between latent and actively replicating HHV-6 and should allow insight into the pathogenesis of this ubiquitous virus.