Cortisol awakening response and negative emotionality linked to asymmetry in major limbic fibre bundle architecture.

The limbic system plays an important role in regulating the hypothalamic-pituitary-adrenal (HPA) axis as well as aspects of emotion, and both neuroendocrine disturbance and increased negative emotionality are associated with risk for developing affective disorders. However, the extent to which the architecture of connections between limbic structures may be linked to individual differences in basal HPA-axis reactivity and negative emotionality is unknown. Here we tested the hypotheses that microstructural asymmetry of the major limbic fibre bundles would be associated with cortisol awakening response (CAR) and neuroticism, a personality trait associated with the tendency to experience negative emotions. Sixty-nine healthy adults were studied with diffusion-weighted imaging, and fractional anisotropy (FA) was extracted from the cingulum and uncinate fasciculus. Higher neuroticism scores, which were associated with higher CAR, were also correlated with higher right relative to left cingulum FA. Elevated CAR was associated with the degree of FA asymmetry within both the cingulum and the uncinate fasciculus, but in opposing directions. These results suggest that the balance between left- and right-sided limbic circuits may bear an important relationship to hypothalamic-pituitary-adrenal axis reactivity, and to the tendency to experience negative emotions, and they raise important questions about the significance of limbic system architecture.

Midlife Cognitive Ability, Education, and Tooth Loss in Older Danes.

OBJECTIVE: To examine the possible influence of cognitive ability and education at age 50 or 60 on number of teeth at age 70. SETTING: Community-dwelling population in Copenhagen, Denmark. PARTICIPANTS: Men and women born in 1914 (N = 302). MEASUREMENTS: Cognitive ability was assessed using the Wechsler Adult Intelligence Scale at age 50 or 60. A global cognitive ability measure was used as a continuous measure and according to tertile. Information on education was gathered using a questionnaire at age 50 or 60. A clinical oral examination took place at age 70, and oral health was measured according to number of teeth (<6 vs ≥6). Baseline covariates were smoking, alcohol, sex, and income. RESULTS: Logistic regression analyses revealed that greater cognitive ability and educational attainment had a protective effect against risk of tooth loss. The associations were significant and persisted after adjusting for confounders and a two-way interaction between cognitive ability and education. CONCLUSION: Higher education level and cognitive ability measured at age 50 or 60 were associated with having more teeth at age 70. Whether these findings are due to the interaction of these factors with oral health, related socioeconomic factors, or other factors remains to be studied.

Elevated p16ink4a Expression in Human Labial Salivary Glands as a Potential Correlate of Cognitive Aging in Late Midlife.

BACKGROUND: The cell-cycle inhibitor and tumor suppressor cyclin dependent kinase inhibitor, p16ink4a, is one of the two gene products of the ink4a/ARF (cdkn2a) locus on chromosome 9q21. Up-regulation of p16ink4a has been linked to cellular senescence, and findings from studies on different mammalian tissues suggest that p16ink4a may be a biomarker of organismal versus chronological age. OBJECTIVE: The aim of this study was to examine the immunolocalization pattern of p16ink4a in human labial salivary gland (LSG) tissue, and to analyze whether its expression level in LSGs is a peripheral correlate of cognitive decline in late midlife. METHODS: The present study was a part of a study of causes and predictors of cognitive decline in middle-aged men in a Danish birth cohort. It is based on data from 181 male participants from the Danish Metropolit birth cohort, born in 1953, who were examined for age-associated alterations in cognition, dental health, and morphological and autonomic innervation characteristics of the LSGs. The participants were allocated to two groups based on the relative change in cognitive performance from young adulthood to late midlife. LSG biopsies were analyzed by qRT-PCR for the expression level of p16ink4a. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of LSGs. RESULTS: p16ink4a immunoreactivity was observed in LSG ductal, myoepithelial, and stromal cells, but not in acinar cells. The mean relative expression of p16ink4a in LSGs was higher in the group of participants with decline in cognitive performance. A logistic regression analysis revealed that the relative p16 expression was predictive of the participant's group assignment. A negative correlation was found between relative p16ink4a expression and the participant's standardized regression residuals from early adulthood to late midlife cognitive performance scores. CONCLUSIONS: p16ink4a expression in human LSGs may constitute a potential peripheral correlate of cognitive decline. Human labial salivary glands seem suitable for studies on organismal as opposed to chronological age.

Smoking and drinking as risk indicators for tooth loss in middle-aged Danes.

OBJECTIVES: To investigate tobacco and alcohol consumption as risk indicators for missing teeth in late middle-aged Danes. METHOD: In all, 1,517 Copenhagen Aging and Midlife Biobank (CAMB) participants received a clinical oral examination that included number of teeth. Information on smoking, drinking, and various covariates was obtained using self-administered, structured questionnaires. Descriptive statistics and logistic regression (dependent variable: 6+ vs. <6 missing teeth) were used to investigate smoking and drinking in relation to missing teeth. RESULTS: Current smokers, persons who currently or previously smoked >15 tobacco units/day, and persons who had smoked for 27+ years had elevated mean scores of missing teeth and associated odds ratios (OR) compared with never smokers. Relative to nondrinkers, alcohol consumption was associated with reduced odds of missing 6+ teeth. DISCUSSION: Our findings suggest that smoking is positively associated, while alcoholic beverage consumption is inversely related to tooth loss in middle-aged Danes.

Associations between xerostomia, histopathological alterations, and autonomic innervation of labial salivary glands in men in late midlife.

OBJECTIVE: One aim of the present study was to investigate whether symptoms of oral dryness (xerostomia) during daytime, assessed in a study group of middle-aged male positive and negative outliers in cognition scores, were associated with age-related degenerative changes in human labial salivary glands and with quantitative measures of the glandular autonomic innervation. Another aim was to study the relation between the autonomic innervation and loss of secretory acinar cells in these glands. METHODS: Labial salivary gland biopsies were taken from the lower lip from 190 men, born in 1953 and members of the Danish Metropolit birth cohort, who were examined for age-related changes in cognitive function and dental health as part of the Copenhagen University Center for Healthy Aging clinical neuroscience project. The glands were routinely processed and semi-quantitatively analyzed for inflammation, acinar atrophy, fibrosis, and adipocyte infiltration. Sections of labial salivary gland tissue were stained with the panneuronal marker PGP 9.5. In a subsample of 51 participants, the autonomic innervation of the glands was analyzed quantitatively by use of stereology. RESULTS: Labial salivary gland tissue samples from 33% of all participants displayed moderate to severe acinar atrophy and fibrosis (31%). Xerostomia was not significantly associated with structural changes of labial salivary glands, but in the subsample it was inversely related to the total nerve length in the glandular connective tissue. Acinar atrophy and fibrosis were negatively correlated with the parenchymal innervation and positively related to diffuse inflammation. CONCLUSIONS: The results from the present study indicate that aspects of the autonomic innervation of labial salivary glands may play a role in the occurrence of xerostomia which in the present study group was not significantly associated with degenerative changes in these glands. The findings further indicate that the integrity of labial salivary gland acini is related to the parenchymal autonomic innervation, whereas inflammatory processes may compromise it by alternative mechanisms.

Dental status and dental caries in 85-year-old Danes.

OBJECTIVES: This study reports findings on the dental status and the prevalence of dental caries among a group of 85-year-old Danes from the Glostrup 1914 Cohort, Denmark. The purpose of the study was to analyse whether caries experience was related to number of teeth and to indicators of functional ability and cognitive function. METHODS: A total of 191 individuals (78 men and 113 women) participated in a cross-sectional population study conducted in 2000. Using mobile dental equipment, a clinical oral examination and an interview were administered to all participants in their homes. Functional ability was measured by the Mob-H scale and cognitive function was assessed by the Mini-Mental State Examination. RESULTS: Fifty-nine per cent of the participants had their own natural teeth and for the dentate participants, the mean number of teeth was 13 (range 1-27). A high prevalence of active caries on coronal and root surfaces was observed. Older adults with few natural teeth had a higher prevalence of active coronal and root caries and a higher unmet treatment need than older adults with many teeth. Further, the study showed that 85-year-old persons with reduced functional ability and cognitive impairment tended to have more active caries than 85-year-olds with no impairment. CONCLUSIONS: A substantial proportion of 85-year-old individuals had retained a natural dentition; however, active dental caries is a problem of concern among the most elderly.