Facets of Personality and Risk of Cognitive Impairment: Longitudinal Findings in a Rural Community from Sardinia.

BACKGROUND: Few studies have examined the associations between personality facets and dementia risk and rarely included individuals from rural settings or with low education. OBJECTIVE: To examine the association between personality and the risk of cognitive impairment. METHODS: Participants (N = 1,668; age 50 to 94 at baseline; 56.4% women; 86.5% less than high school diploma) were from a rural region of Sardinia (Italy) who completed the Revised NEO Personality Inventory (NEO-PI-R) during the first wave (2001-2004) and the Mini-Mental State Examination (MMSE) at waves two to five (2005-2021). Cox regression was used to test personality and covariates as predictors of cognitive impairment based on MMSE education-adjusted cutoffs. RESULTS: During the up to 18-year follow-up (M = 10.38; SD = 4.76), 187 individuals (11.2%) scored as cognitively impaired. Participants with higher neuroticism (particularly the depression facet [HR = 1.22, 95% CI = 1.06-1.40]), and lower agreeableness (particularly the modesty facet [HR = 0.83, 95% CI = 0.71-0.97]) and lower conscientiousness (particularly the dutifulness facet [HR = 0.78, 95% CI = 0.67-0.92]) were at higher risk of cognitive impairment. Lower warmth ([HR = 0.75, 95% CI = 0.65-0.87], facet of extraversion) and ideas ([HR = 0.76, 95% CI = 0.65-0.89], facet of openness) were also associated with increased risk of impairment. These associations were virtually unchanged in models that accounted for other risk factors, including smoking, depression, obesity, hypertension, diabetes, and apolipoprotein E (APOE) ɛ4 carrier status. Across the five domains, sex and the APOE variant did not moderate the associations. CONCLUSION: In a sample with demographic characteristics underrepresented in dementia research, this study identifies personality domains and facets most relevant to the risk of cognitive impairment.

Prevalence of unknown thyroid disorders in a Sardinian cohort.

OBJECTIVE: To assess thyroid function, the presence of thyroid antibodies, as well as the presence of goiter and/or nodules in subjects without a prior diagnosis of thyroid disorders, in a region with mild to moderate iodine deficiency. DESIGN AND METHODS: This cross-sectional study is based on data obtained from first and third visits of participants in the Sardinian survey. We performed two different analyses. In one, we assessed the prevalence of unknown thyroid dysfunctions among 6252 subjects who had a medical examination and blood collection for assays of thyrotropin, free thyroxine, and antibodies against thyroperoxidase (AbTPO) and against thyroglobulin (AbTG). In a second analysis, we evaluated the frequency of undiagnosed goiter and nodules among 3377 subjects who had a thyroid ultrasound scan. Subjects were excluded if they had a previous history of thyroid disorders or presence of goiter and/or nodules, or thyroid surgery, or if they were taking drugs that could impair thyroid function. RESULTS: We found a low prevalence of overt thyroid dysfunction (hyperthyroidism 0.4% and hypothyroidism 0.7%). The rates of subclinical hypothyroidism and hyperthyroidism were 4.7 and 2.4% respectively. Almost 16% of participants were positive for at least one antibody and 5.2% for both AbTG and AbTPO. Nodules were detected in 17.4% of subjects and the prevalence of goiter was 22.1%. CONCLUSIONS: Undiagnosed biochemical thyroid dysfunctions, unknown nodules, and goiter were common in subjects living in a mild to moderate iodine-deficient area. In this community, thyroid disorders often go undetected and screening could be reasonable in subjects at a higher risk.

Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function.

Thyroid-stimulating hormone (TSH) controls thyroid growth and hormone secretion through binding to its G protein-coupled receptor (TSHR) and production of cyclic AMP (cAMP). Serum TSH is a sensitive indicator of thyroid function, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over a life span. By genotyping 362,129 SNPs in 4,300 Sardinians, we identified a strong association (p = 1.3 x 10(-11)) between alleles of rs4704397 and circulating TSH levels; each additional copy of the minor A allele was associated with an increase of 0.13 muIU/ml in TSH. The single-nucleotide polymorphism (SNP) is located in intron 1 of PDE8B, encoding a high-affinity cAMP-specific phosphodiesterase. The association was replicated in 4,158 individuals, including additional Sardinians and two genetically distant cohorts from Tuscany and the Old Order Amish (overall p value = 1.9 x 10(-20)). In addition to association of TSH levels with SNPs in PDE8B, our genome scan provided evidence for association with PDE10A and several biologically interesting candidates in a focused analysis of 24 genes. In particular, we found evidence for association of TSH levels with SNPs in the THRB (rs1505287, p = 7.3 x 10(-5)), GNAQ (rs10512065, p = 2.0 x 10(-4)), TG (rs2252696, p = 2.2 x 10(-3)), POU1F1 (rs1976324, p = 3.9 x 10(-3)), PDE4D (rs27178, p = 8.3 x 10(-3)), and TSHR (rs4903957, p = 8.6 x 10(-3)) loci. Overall, the results suggest a primary effect of PDE8B variants on cAMP levels in the thyroid. This would affect production of T4 and T3 and feedback to alter TSH release by the pituitary. PDE8B may thus provide a candidate target for the treatment of thyroid dysfunction.