Cognitive reserve and mortality in dementia: the role of cognition, functional ability and depression

OBJECTIVE: This study examined whether dementia patients with greater cognitive reserve had increased mortality rates, and whether this association was different across strata of cognition, functional ability and depression. METHODS: In the community-based Amsterdam Study of the Elderly, 261 non-institutionalized dementia patients, identified using the Geriatric Mental State Schedule (GMS), were followed for an average of 55.5 months after which mortality data were obtained. Cognitive reserve was indicated by years of education and pre-morbid intelligence (measured using the Dutch Adult Reading Test). Cognition, functional ability and depression were indicated by Mini-Mental State scores, ADL and IADL measurements and GMS depressive syndrome, respectively. RESULTS: During the follow-up 146 persons (55.9%) died. Cox regression analyses showed that more highly educated dementia patients had higher mortality rates, only if they had low MMSE scores or if they had a concurrent depression. Pre-morbid intelligence was associated with a higher mortality rate, independent of cognition, but this association was much stronger among patients with depression. The positive association between education or intelligence and mortality was not modified by functional disabilities. CONCLUSIONS: The results suggest that dementia patients with greater cognitive reserve have increased mortality rates, only if the disease has progressed to such an extent that clinical symptoms are more severe. In this respect, the reserve hypothesis needs a modification. Depression in dementia patients with greater cognitive reserve may reflect a subgroup of patients with poor prognosis.     

Association of ambient air‐pollution levels with acute asthma exacerbation among children in Singapore

BACKGROUND: Air-pollution levels have been shown to be associated with increased morbidity of respiratory diseases. METHODS: Data for ambient air-pollutant levels, meteorologic factors, and hospitalization or emergency room (ER) visits for acute asthma in Singapore children over a 5-year period (1990-4) were obtained and analyzed for associations by time-series methods. RESULTS: Throughout this period, the annual mean and 24-h mean levels for sulfur dioxide (SO2), nitrogen dioxide (NO2), and total suspended particles (TSP) and maximum 1-h daily average for ozone were generally within the air-quality guidelines established by the World Health Organization (WHO). However, positive correlation between levels of each of these pollutants and daily ER visits for asthma was observed in children aged 3-12 years, but not among adolescents and young adults (13-21 years old). The association with SO2 and TSP persisted after standardization for meteorologic and temporal variables. An adjusted increase in 2.9 ER visits for every 20 microg/m3 increase in atmospheric SO2 levels, lagged by 1 day, was observed on days when levels were above 68 microg/m3. With TSP, an adjusted increase of 5.80 ER visits for every 20 microg/m3 increase in its daily atmospheric levels, lagged by 1 day, was observed on days with levels above 73 microg/m3. Similar results were also obtained after controlling for autocorrelation by time-series analysis. CONCLUSIONS: These associations were observed even though the overall levels of all pollutants were generally within the air-quality guidelines established by the WHO. These findings suggest that asthmatic children are susceptible to increased levels of air pollutants, particularly SO2 and TSP, although the ambient levels are generally within "acceptable" ranges.     

Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.     

Piccolo genotype modulates neural correlates of emotion processing but not executive functioning

Major depressive disorder (MDD) is characterized by affective symptoms and cognitive impairments, which have been associated with changes in limbic and prefrontal activity as well as with monoaminergic neurotransmission. A genome-wide association study implicated the polymorphism rs2522833 in the piccolo (PCLO) gene—involved in monoaminergic neurotransmission—as a risk factor for MDD. However, the role of the PCLO risk allele in emotion processing and executive function or its effect on their neural substrate has never been studied. We used functional magnetic resonance imaging (fMRI) to investigate PCLO risk allele carriers vs noncarriers during an emotional face processing task and a visuospatial planning task in 159 current MDD patients and healthy controls. In PCLO risk allele carriers, we found increased activity in the left amygdala during processing of angry and sad faces compared with noncarriers, independent of psychopathological status. During processing of fearful faces, the PCLO risk allele was associated with increased amygdala activation in MDD patients only. During the visuospatial planning task, we found no genotype effect on performance or on BOLD signal in our predefined areas as a function of increasing task load. The PCLO risk allele was found to be specifically associated with altered emotion processing, but not with executive dysfunction. Moreover, the PCLO risk allele appears to modulate amygdala function during fearful facial processing in MDD and may constitute a possible link between genotype and susceptibility for depression via altered processing of fearful stimuli. The current results may therefore aid in better understanding underlying neurobiological mechanisms in MDD.     

Measures of physical performance and risk for progressive and catastrophic disability: results from the Women's Health and Aging Study

BACKGROUND: Physical performance measures can predict incident disability, but little research has assessed and compared how these measures predict progressive and rapid-onset (catastrophic) disability. The authors evaluated the ability of upper and lower extremity performance measures to predict progressive and catastrophic disability in activities of daily living (ADL), mobility, and upper extremity function. METHODS: The incidence of progressive and catastrophic disability was assessed semiannually during a 3-year period in 884 women participating in the Women's Health and Aging Study I. Four-meter walking speed, balance, and chair stands tests were used to evaluate lower extremity function. The putting-on-blouse test, the Purdue pegboard test, and grip strength were used to assess upper extremity function. Summary performance scores (SPS) for the lower and upper extremities were calculated. Among participants in whom disability developed, those who reported no difficulty in the previous year were defined as cases of catastrophic disability, and those who previously reported little or some difficulty were considered to be cases of progressive disability. Cox proportional hazard regression analyses were used to evaluate the association of performance measures and time to incident disability. The predictive ability of performance measures was compared using receiver-operator characteristic curves. RESULTS: All lower and upper extremity measures, with the exception of grip strength, significantly predicted the onset of progressive ADL disability, but only walking speed was significantly associated with the onset of catastrophic ADL disability. The chair stands test, walking speed, and the lower extremity SPS were significantly associated with the onset of both progressive and catastrophic mobility disability. Only lower extremity individual tests and SPS significantly predicted the onset of both progressive and catastrophic upper extremity disability. The receiver-operator characteristic curves for ADL and mobility disability showed that all performance measures evaluated had a greater predictive ability for progressive than for catastrophic incident disability. This finding was not consistent for upper extremity disability. The areas under the curve for walking speed and lower extremity SPS were very similar, ranging from 0.58 to 0.81 and from 0.57 to 0.85, and the predictive ability of these two measures was the greatest for all disability outcomes assessed. CONCLUSION: Physical performance measures of lower extremity and, in particular, walking speed and lower extremity SPS are valuable tools to predict different forms of disability, especially those with a progressive onset.     

Brief Report: Educational attainment does not influence brain aging

Education has been related to various advantageous lifetime outcomes. Here, using longitudinal structural MRI data (4,422 observations), we tested the influential hypothesis that higher education translates into slower rates of brain aging. Cross-sectionally, education was modestly associated with regional cortical volume. However, despite marked mean atrophy in the cortex and hippocampus, education did not influence rates of change. The results were replicated across two independent samples. Our findings challenge the view that higher education slows brain aging.