Subclinical atherosclerotic calcification and cognitive functioning in middle-aged adults: The CARDIA study

Objective

Cardiovascular risk factors in middle-age are associated with cognitive impairment and dementia in older age. Less is known about the burden of calcified subclinical atherosclerosis and cognition, especially in midlife. We examined the association of coronary artery and abdominal aortic calcified plaque (CAC and AAC, respectively) with cognitive functioning in middle-aged adults.

Methods

This cross-sectional study included 2510 black and white adults (age: 43–55 years) without heart disease or stroke who completed a year 25 follow-up exam (2010–11) as part of the Coronary Artery Risk Development in Young Adults Study. CAC and AAC were measured with non-contrast computed tomography. Cognition was assessed with the Digit Symbol Substitution Test (DSST) (psychomotor speed), Stroop Test (executive function), and Rey Auditory Verbal Learning Test (RAVLT) (verbal memory).

Results

A greater amount of CAC and AAC was associated with worse performance on each test of cognitive function after adjustment for age, sex, race, education, and study center. Associations were attenuated, but remained significant for the DSST and RAVLT following additional adjustment for vascular risk factors, including adiposity, smoking, alcohol use, dyslipidemia, hypertension, and diabetes. Compared to participants without CAC or AAC, those with both CAC and AAC, but not CAC or AAC alone was associated with lower DSST scores (p < 0.05).

Conclusions

In this community-based sample, greater subclinical atherosclerotic calcification was associated with worse psychomotor speed and memory in midlife. These findings underscore the importance of a life course approach to the study of cognitive impairment with aging.     

Older adults discharged from the hospital with delirium: 1-year outcomes

OBJECTIVES: To compare 1-year institutionalization and mortality rates of patients who were delirious at discharge, patients whose delirium resolved by discharge, and patients who were never delirious in the hospital. DESIGN: Secondary analysis of prospective cohort data from the Delirium Prevention Trial. SETTING: General medicine service at Yale New Haven Hospital, March 25, 1995, through March 18, 1998, with follow-up interviews completed in 2000. PARTICIPANTS: Four hundred thirty-three patients aged 70 and older who were not delirious at admission. MEASUREMENTS: Patients underwent daily assessments of delirium from admission to discharge using the Confusion Assessment Method. Nursing home placement and mortality were determined at 1-year follow up. RESULTS: Of the 433 study patients, 24 (5.5%) had delirium at discharge, 31 (7.2%) had delirium that resolved during hospitalization, and 378 (87.3%) were never delirious. After 1 year of follow-up, 20 of 24 (83.3%) patients discharged with delirium, 21 of 31 (67.7%) patients whose delirium resolved, and 157 of 378 (41.5%) patients who were never delirious were admitted to a nursing home or died. Compared with patients who were never delirious, patients with delirium at discharge had a multivariable adjusted hazard ratio (HR) of 2.64 (95% confidence interval (CI)=1.60-4.35) for nursing home placement or mortality, whereas resolved cases had a HR of 1.53 (95% CI=0.96-2.43). CONCLUSION: Delirium at discharge is associated with a high rate of nursing home placement and mortality over a 1-year follow-up period. Interventions to increase detection of delirium and improvements in transitional care may help reduce these negative outcomes.     

ERP correlates of error monitoring in 10-year olds are related to socialization

Research suggests that the anterior cingulate cortex (ACC) generates the error-related negativity (ERN or Ne), an event-related potential component that reflects response monitoring and is influenced by individual differences in personality. The present study examined the relation between personality as indexed by the Junior Eysenck Personality Questionnaire (Extraversion, Neuroticism, Psychoticism, and Lie scale) and the ERN in 10-year-old children. High scores on the Psychoticism and low scores on the Lie scale, which are taken to reflect low socialization in children, were associated with smaller ERNs. Results lend support to previous studies finding this association in adults. We argue that the ERN may be an indirect measure of ACC activity and is affected by one's concern with task performance. The results of the present study extend findings previously reported in adults to a population of normally developing children and show that similar mechanisms of performance monitoring may underlie individual differences in personality across development.     

Increased alpha suppression with age during involuntary memory retrieval

Recent work suggests that while voluntary episodic memory declines with age, involuntary episodic memory, which comes to mind spontaneously without intention, remains relatively intact. However, the neurophysiology underlying these differences has yet to be established. The current study used electroencephalography (EEG) to investigate voluntary and involuntary retrieval in older and younger adults. Participants first encoded sounds, half of which were paired with pictures, the other half unpaired. EEG was then recorded as they listened to the sounds, with participants in the involuntary group performing a sound localization cover task, and those in the voluntary group additionally attempting to recall the associated pictures. Participants later reported which sounds brought the paired picture to mind during the localization task. Reaction times on the localization task were slower for voluntary than involuntary retrieval and for paired than unpaired sounds, possibly reflecting increased attentional demands of voluntary retrieval and interference from reactivation of the associated pictures respectively. For the EEG analyses, young adults showed greater alpha event-related desynchronization (ERD) during voluntary than involuntary retrieval at frontal and occipital sites, while older adults showed pronounced alpha ERD regardless of intention. Additionally, older adults showed greater ERD for paired than unpaired sounds at occipital sites, likely reflecting visual reactivation of the associated pictures. Young adults did not show this alpha ERD memory effect. Taken together, these data suggest that involuntary memory is largely preserved with age, but this may be due to older adults' greater recruitment of top-down control even when demand for such control is limited.     

Nicotine activates TRPM5-dependent and independent taste pathways

The orosensory responses elicited by nicotine are relevant for the development and maintenance of addiction to tobacco products. However, although nicotine is described as bitter tasting, the molecular and neural substrates encoding the taste of nicotine are unclear. Here, rats and mice were used to determine whether nicotine activates peripheral and central taste pathways via TRPM5-dependent mechanisms, which are essential for responses to other bitter tastants such as quinine, and/or via nicotinic acetylcholine receptors (nAChRs). When compared with wild-type mice, Trpm5^−/− mice had reduced, but not abolished, chorda tympani (CT) responses to nicotine. In both genotypes, lingual application of mecamylamine, a nAChR-antagonist, inhibited CT nerve responses to nicotine and reduced behavioral responses of aversion to this stimulus. In accordance with these findings, rats were shown to discriminate between nicotine and quinine presented at intensity-paired concentrations. Moreover, rat gustatory cortex (GC) neural ensemble activity could also discriminate between these two bitter tastants. Mecamylamine reduced both behavioral and GC neural discrimination between nicotine and quinine. In summary, nicotine elicits taste responses through peripheral TRPM5-dependent pathways, common to other bitter tastants, and nAChR-dependent and TRPM5-independent pathways, thus creating a unique sensory representation that contributes to the sensory experience of tobacco products.     

Interrelationship of micromechanics and morphology of fibroblasts adhered on different polymeric surfaces

The membrane stiffness (ε) of rat lung fibroblasts (RLFs) adhered on different polymeric surfaces was probed by atomic force microscopy. The corresponding cell morphology was also analyzed to probe its interrelationship with ε. Two tyrosine-derived polymer families, poly(DTR glutarate)s and poly(DTE-co-PEG₁₀₀₀ carbonate)s with systematic variations in the chemical composition and physical properties, notably surface hydrophilicity, were used. The cell membrane of adhered RLFs was indented by a probe tip. ε was obtained by best-fitting the relationship of applied tip forces and the indentation depth with the Hertz model. Excluding tissue culture polystyrene, non-PEG-containing polymers are generally hydrophobic and the changes in chemical composition do not elicit significant changes in ε. In contrast, polymers containing as little as 2 mol.% PEG display a major increase in surface hydrophilicity and invoke a substantial decrease in ε. Additionally, RLFs show a high degree of spreading and fibroblastic appearance on non-PEG-containing polymers, but much less spreading and axial morphology when PEG is present. A mechanism is proposed to explain how a cell maintains its structural integrity on different polymeric surfaces: the degree of cell spreading is higher on non-PEG-containing surfaces than on PEG-containing ones, resulting in more extended cytoskeletal filaments and hence a stiffer cell membrane. Our studies shed light on the use of cellular micromechanics, and in particular membrane stiffness, to characterize cell response as a function of the chemical composition of the underlying substrata.     

X-linked insertion/deletion polymorphisms: forensic applications of a 33-markers panel

Insertion/deletion (INDEL) polymorphisms are diallelic markers with potential characteristics for use in forensics and biological anthropology, including: the simplicity of laboratory analysis, the possibility of genotyping many markers in a single PCR multiplex reaction, as well as analyzing markers with special inheritance types, such as those linked to the X chromosome (X-INDEL). In this work we developed a laboratory analysis methodology using a 33-INDEL marker panel for the X chromosome in a single PCR multiplex reaction, followed by a capillary electrophoresis run. We employed the panel to genotype a sample of 351 individuals of a mixed population from the Brazilian Amazon. The results demonstrate that the measurement of biostatistical parameters for forensic use in this population is compatible with prior estimates from other populations using current X-STR panels.