Demographic and Lifestyle Characteristics, but Not Apolipoprotein E Genotype, Are Associated with Intelligence among Young Chinese College Students

<div><p>Background</p><p>Intelligence is an important human feature that strongly affects many life outcomes, including health, life-span, income, educational and occupational attainments. People at all ages differ in their intelligence but the origins of these differences are much debated. A variety of environmental and genetic factors have been reported to be associated with individual intelligence, yet their nature and contribution to intelligence differences have been controversial.</p><p>Objective</p><p>To investigate the contribution of apolipoprotein E (<i>APOE</i>) genotype, which is associated with the risk for Alzheimer’s disease, as well as demographic and lifestyle characteristics, to the variation in intelligence.</p><p>Methods</p><p>A total of 607 Chinese college students aged 18 to 25 years old were included in this prospective observational study. The Chinese revision of Wechsler Adult Intelligence Scale (the fourth edition, short version) was used to determine the intelligence level of participants. Demographic and lifestyle characteristics data were obtained from self-administered questionnaires.</p><p>Results</p><p>No significant association was found between <i>APOE</i> polymorphic alleles and different intelligence quotient (IQ) measures. Interestingly, a portion of demographic and lifestyle characteristics, including age, smoking and sleep quality were significantly associated with different IQ measures.</p><p>Conclusions</p><p>Our findings indicate that demographic features and lifestyle characteristics, but not <i>APOE</i> genotype, are associated with intelligence measures among young Chinese college students. Thus, although <i>APOE</i> ε4 allele is a strong genetic risk factor for Alzheimer’s disease, it does not seem to impact intelligence at young ages.</p></div

Linkage disequilibrium between SNPs in controls as measured by pairwise r² values.

<p>Values are given as percentages out of a maximum of 100. Solid black boxes indicate an r² value of 100.</p

Single SNP associations with PD.

<p>PD = Parkinson's disease. SNP = single nucleotide polymorphism. MA = minor allele. OR = odds ratio. CI = confidence interval. *Chromosomal positions based on the February 2009 (GRCH37/hg19) genome assembly [<i>SNCA</i> is located at Chr4;90,645,251–90,759,447]. ORs, 95% CIs, and p-values result from logistic regression models adjusted for age and gender. ORs correspond to presence vs. absence of the minor allele.</p

Associations of subject demographic and lifestyle characteristics with IQ score measures (PSI and PRI) from multivariable analysis.

<p>Regression coefficients, 95% CIs, and p values were calculated from multivariable linear regression models. Regression coefficients are interpreted as the change in the mean IQ measure corresponding to the increase specified in parenthesis (continuous variables) or presence of the given characteristic (categorical variables). For all variables except height, weight, and BMI, models were adjusted for age, gender, height, weight, BMI, personality, smoking, alcohol consumption, physical exercise, and sleep quality. For height, weight, and BMI, models were adjusted for age, gender, personality, smoking, alcohol consumption, physical exercise, and sleep quality. P values of 0.005 or lower were considered as statistically significant after applying a Bonferroni correction for multiple testing. CI = confidence interval.</p><p>Associations of subject demographic and lifestyle characteristics with IQ score measures (PSI and PRI) from multivariable analysis.</p

Associations between <i>APOE</i> ε4 and IQ score measures.

<p>Regression coefficients, 95% CIs, and p values were calculated from linear regression models. Regression coefficients are interpreted as the difference in means of the given IQ measure between carriers and non-carriers of the ε4 allele (i.e. ε4 allele present vs. ε4 allele not present). A regression coefficient greater than “0” indicates a higher value of the given measure for ε4 carriers, and a regression coefficient less than “0” indicates a lower value of the given measure for ε4 carriers. Multivariable models were adjusted for school (Xiamen University or AnFang College), age, gender, height, weight, BMI, personality, smoking, drinking alcohol, physical exercise, and sleep quality. P values of 0.01 or lower were considered as statistically significant after applying a Bonferroni correction for multiple testing. Min = Minimum; Q1 = first quartile; Q3 = third quartile; Max = Maximum; CI = confidence interval.</p><p>Associations between <i>APOE</i> ε4 and IQ score measures.</p

Associations between <i>APOE</i> ε2 and IQ score measures.

<p>Regression coefficients, 95% CIs, and p values were calculated from linear regression models. Regression coefficients are interpreted as the difference in means of the given IQ measure between carriers and non-carriers of the ε2 allele (i.e. ε2 allele present vs. ε2 allele not present). A regression coefficient greater than “0” indicates a higher value of the given measure for ε2 carriers, and a regression coefficient less than “0” indicates a lower value of the given measure for ε2 carriers. Multivariable models were adjusted for school (Xiamen University or AnFang College), age, gender, height, weight, BMI, personality, smoking, drinking alcohol, physical exercise, and sleep quality. P values of 0.01 or lower were considered as statistically significant after applying a Bonferroni correction for multiple testing. Min = Minimum; Q1 = first quartile; Q3 = third quartile; Max = Maximum; CI = confidence interval.</p><p>Associations between <i>APOE</i> ε2 and IQ score measures.</p

Associations of subject demographic and lifestyle characteristics with IQ score measures (Full Scale IQ Score, VCI, and WMI) from multivariable analysis.

<p>Regression coefficients, 95% CIs, and p values were calculated from multivariable linear regression models. Regression coefficients are interpreted as the change in the mean IQ measure corresponding to the increase specified in parenthesis (continuous variables) or presence of the given characteristic (categorical variables). For all variables except height, weight, and BMI, models were adjusted for age, gender, height, weight, BMI, personality, smoking, alcohol consumption, physical exercise, and sleep quality. For height, weight, and BMI, models were adjusted for age, gender, personality, smoking, alcohol consumption, physical exercise, and sleep quality. P values of 0.005 or lower were considered as statistically significant after applying a Bonferroni correction for multiple testing. CI = confidence interval.</p><p>Associations of subject demographic and lifestyle characteristics with IQ score measures (Full Scale IQ Score, VCI, and WMI) from multivariable analysis.</p

Age- and disease-dependent increase of the mitophagy marker phospho-ubiquitin in normal aging and Lewy body disease

<p>Although exact causes of Parkinson disease (PD) remain enigmatic, mitochondrial dysfunction is increasingly appreciated as a key determinant of dopaminergic neuron susceptibility in both familial and sporadic PD. Two genes associated with recessive, early-onset PD encode the ubiquitin (Ub) kinase PINK1 and the E3 Ub ligase PRKN/PARK2/Parkin, which together orchestrate a protective mitochondrial quality control (mitoQC) pathway. Upon stress, both enzymes cooperatively identify and decorate damaged mitochondria with phosphorylated poly-Ub (p-S65-Ub) chains. This specific label is subsequently recognized by autophagy receptors that further facilitate mitochondrial degradation in lysosomes (mitophagy). Here, we analyzed human post-mortem brain specimens and identified distinct pools of p-S65-Ub-positive structures that partially colocalized with markers of mitochondria, autophagy, lysosomes and/or granulovacuolar degeneration bodies. We further quantified levels and distribution of the ‘mitophagy tag’ in 2 large cohorts of brain samples from normal aging and Lewy body disease (LBD) cases using unbiased digital pathology. Somatic p-S65-Ub structures independently increased with age and disease in distinct brain regions and enhanced levels in LBD brain were age- and Braak tangle stage-dependent. Additionally, we observed significant correlations of p-S65-Ub with LBs and neurofibrillary tangle levels in disease. The degree of co-existing p-S65-Ub signals and pathological PD hallmarks increased in the pre-mature stage, but decreased in the late stage of LB or tangle aggregation. Altogether, our study provides further evidence for a potential pathogenic overlap among different forms of PD and suggests that p-S65-Ub can serve as a biomarker for mitochondrial damage in aging and disease.</p> <p><b>Abbreviations:</b> BLBD: brainstem predominant Lewy body disease; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; DLB: dementia with Lewy bodies; DLBD: diffuse neocortical Lewy body disease; EOPD: early-onset Parkinson disease; GVB: granulovacuolar degeneration body; LB: Lewy body; LBD: Lewy body disease; mitoQC: mitochondrial quality control; nbM: nucleus basalis of Meynert; PD: Parkinson disease; PDD: Parkinson disease with dementia; p-S65-Ub: PINK1-phosphorylated serine 65 ubiquitin; SN: substantia nigra; TLBD: transitional Lewy body disease; Ub: ubiquitin </p