Sukupuolierot kognitiivisissa toiminnoissa : tutkimus kaksosilla

Studies concerning cognitive sex differences have indicated that, on average, females outperform males in some verbal abilities, whereas males outperform females in some visual-spatial abilities. Prenatal hormones play important role in sexual differentiation. Presence of androgens is believed to cause male brain differentiation. According to animal studies prenatal exposure to testosterone in females can result in masculinized behaviour or physiological traits. Human studies of possible masculinization of females from opposite-sex twin pairs are controversial. Some studies have indicated that female members of opposite-sex twins may be masculinized in some traits, while other studies show no evidence of masculinization. Hence the aim of the present study is to investigate sex differences and possible masculinization of cognitive functions in young adult twins. Subjects (N=336) were recruited from the ongoing longitudinal FinnTwin16 study of Finnish twins born in 1974-1979. Results indicate female superiority in verbal and executive functions and male superiority in visual and working memory functions. Further, in female members of opposite-sex twin pairs the visual abilities were enhanced to the male level. However, they still outperformed males in verbal and executive functions. In male members of opposite-sex twin pairs there were no signs of better performance in functions that favored females. Nor there were evidence of reduced performance in functions that favored males. This study suggests that there occurs masculinization of cognitive functions in females who have a male co-twin. In contrast, males with female co-twins are not feminized in their cognitive functions. These results indicate some benefits of twinship in female members of opposite-sex twin pairs in cognitive abilities. Whether the masculinization is a result of organizational effects of prenatal testosterone or postnatal environmental influences could not be resolved. Future research, with control over environmental influences, is needed to determine the origin of masculinization of cognitive abilities.Kognitiivisten toimintojen sukupuolieroja koskevat tutkimukset osoittavat naisten olevan keskimäärin miehiä parempia joissakin verbaalisissa kyvyissä, kun taas miehet ovat keskimäärin naisia parempia joissakin visuaalis-spatiaalisissa toiminnoissa. Raskauden aikaiset hormonit ovat tärkeitä sukupuolien erilaistumisessa. Eläintutkimusten mukaan naaraiden altistuminen mieshormoneille raskauden aikana saattaa johtaa fyysisten ominaisuuksien tai käyttäytymisen muuttumisen sellaiseksi, joka on enemmän koiraalle ominaista (maskulinisaatio). Ihmisillä voidaan mahdollista maskulinisaatiota tutkia kaksosilla. On olemassa tutkimuksia, jotka osoittavat maskulinisaatiota naisilla, joilla on kaksosveli. Toisaalta osassa tutkimuksissa ei ole merkkiä siitä, että naiset joilla on kaksosveli, poikkeaisivat muista naisista. Tämän tutkimuksen tarkoitus on selvittää eroavatko naiset, joilla on kaksosveli, niistä naisista joilla on kaksossisko kognitiivisissa toiminnoissa. Tämän tutkimuksen koehenkilöt (N=336) olivat nuoria aikuisia kaksosia käynnissä olevasta suomalaisesta Nuorten Kaksosten Terveystutkimuksesta (FinnTwin16). Koehenkilöt olivat syntyneet 1974-1979. Tulosten mukaan naiset olivat keskimäärin miehiä parempia verbaalisissa tehtävissä ja toiminnan ohjauksessa. Miehet taas olivat keskimäärin naisia parempia visuaalisissa tehtävissä ja kuulonvaraisessa työmuistissa. Eri sukupuolta olevien kaksosparien naisten visuaalinen suoritus oli parantunut samalle tasolle kuin miesten suoritus. Samalla he olivat miehiä parempia verbaalisissa tehtävissä ja toiminnan ohjauksessa. Eri sukupuolta olevien kaksosparien miesten suoritus naisia suosivissa tehtävissä ei ollut parantunut. Eikä heidän suorituksensa miehiä suosivissa tehtävissä ollut huonontunut. Tutkimus osoittaa, että naiset joilla on kaksosveli saattavat olla maskuliinistuneita kognitiivisissa toiminnoissa. Sen sijaan miehet, joilla on kaksossisko, eivät näyttäisi olevan alttiita kognitiivisten toimintojen feminisaatiolle. Tutkimus tuo esiin kaksosuuden hyödyn kognitiivisissa kyvyissä naisilla, joilla on kaksosveli. Vaikka tulokset tukevat hypoteesia, että raskauden aikaisen testosteronille altistumisella on maskulinisoivaa vaikutusta, ei tämän tutkimuksen perusteella voida sanoa johtuuko tämä sittenkään raskauden aikaisesta hormoniympäristöstä vai syntymän jälkeisistä kokemuksista. Tulevissa tutkimuksissa tulisi ottaa huomioon ympäristötekijöitä, jotta voitaisiin selvittää kognitiivisten toimintojen maskuliinistumisen alkuperää

Origins of the sex differences in handedness and mental rotation ability : genetic, environmental and hormonal effects

In humans, well-replicated and robust sex differences in cognitive functions exist for handedness and mental rotation ability. A common characteristic in human cognitive functions is the lateralization of language functions. Handedness is a common measure of laterality and is related to language lateralization. The prevalence of left-handedness is higher in males than in females, the male to female ratio being about 1.2. Among cognitive abilities, the largest sex difference is evident in the Vandenberg and Kuse Mental Rotation Test (MRT), which requires the ability to rotate objects in mental space. On average, males achieve scores one standard deviation higher than females in the MRT. The present thesis investigated the origins of the sex differences in laterality and spatial ability as represented by handedness and mental rotation ability, respectively. Two population-based Finnish twin cohorts were utilized in this study. Handedness was studied in 25 810 twins and 4068 singletons born before 1958 from the Older Finnish Twin Cohort, and in 4736 twins born in 1983-87 from the FinnTwin12. MRT was studied in a sub-sample of 804 young adult participants from the FinnTwin12 sample. The main findings of this study were: 1) the prevalence of left-handedness was higher among males than among females in both singletons and in twins; 2) males had significantly higher scores than females in MRT; 3) about one quarter of the variance in handedness and about half of the variance in MRT was explained by genetic effects, whereas the remainder of the variance in these traits was explained by environmental effects unique to each individual. The magnitude of the genetic effects was similar in both sexes; 4) left-handedness was significantly less common in female co-twins of a male than in female co-twins of a female, and female co-twins of a male scored significantly higher than did female co-twins of a female in the Mental Rotation Test. This dissertation discusses whether these differences between females from opposite- and same-sex twin pairs are due to the prenatal transfer of testosterone from the male fetus in females with male co-twins or whether they arise from postnatal socialization effects.Kognitiivisten toimintojen alueella kaksi selkeää sukupuolieroa ilmenevät kätisyydessä ja avaruudellisen hahmottamisen kyvyssä pyörittää (rotatoida) mielensisäisesti kappaleita. Vasenkätisyys on noin 1,2 kertaa yleisempää miehillä kuin naisilla. Miesten keskimääräinen tulos avaruudellista hahmottamista mittaavassa Mental Rotation Testissä (MRT) on noin yhden keskihajonnan parempi kuin naisilla. Tässä väitöskirjassa tutkittiin sukupuolierojen alkuperää lateraalisuudessa ja avaruudellisessa hahmottamisessa, joita tässä tutkimuksessa edustivat kätisyys ja MRT. Tutkimuksessa käytettiin kahta suomalaista väestöpohjaista kaksosaineistoa: kätisyyttä tutkittiin aineistolla, jossa oli mukana 25 810 ennen vuotta 1958 syntynyttä kaksosta ja 4068 ei-kaksosta sekä kaksosten kehitys ja terveys tutkimus aineistolla, jossa oli mukana 4736 vuosina 1983-87 syntynyttä kaksosta. Avaruudellista hahmottamista käsittäviin tutkimuksiin osallistui 804 nuorta aikuista kaksosten kehitys ja terveys tutkimuksesta. Tärkeimmät tulokset olivat: 1) vasenkätisyys oli miehillä yleisempää kuin naisilla, niin kaksosilla kuin ei-kaksosillakin; 2) mieskaksoset suoriutuivat naiskaksosia paremmin avaruudellista hahmottamista vaativassa tehtävässä; 3) sekä naisilla että miehillä noin neljännes kätisyydessä esiintyvästä vaihtelusta ja noin puolet avaruudellisen hahmottamisen kyvyssä esiintyvästä vaihtelusta selittyivät geneettisillä tekijöillä, yksilöille erilaisten ympäristötekijöiden selittäessä loput näissä ominaisuuksissa esiintyvästä vaihtelusta; 4) vasenkätisyys oli harvinaisempaa naisilla joilla on kaksosveli kuin naisilla joilla on kaksossisar ja lisäksi naiset joilla on kaksosveli suoriutuivat avaruudellista hahmottamista vaativassa tehtävässä merkitsevästi paremmin kuin naiset joilla on kaksossisar. Tämän tutkimuksen perusteella ei voida varmasti sanoa, että johtuvatko viimeksi mainitut erot siitä, että naiskaksoset joilla on veli saattavat altistua kohdussa kaksosveljen tuottamalle testosteronille vai siitä, että syntymän jälkeinen kasvuympäristö on erilainen naisilla joilla on kaksosveli kuin naisilla joilla on kaksossisar

Kognitiivisten toimintojen muutokset - mikä on ikääntymistä, mikä sairautta?

Teema : vanhuuden vallankumous. English summaryPeer reviewe

Immediate verbal recall and familial dementia risk: population-based study of over 4000 twins

Objective To investigate the effect of familial risk for dementia on verbal learning by comparing cognitively healthy twins who had demented co-twins with cognitively healthy twins who had cognitively healthy co-twins. Methods 4367 twins aged >= 65 years including 1375 twin pairs (533 monozygotic (MZ), 823 dizygotic (DZ) and 19 unknown zygosity pairs) from a population-based Finnish Twin Cohort participated in a cross-sectional telephone assessment for dementia and in a single free recall trial of a 10-item word list. Results Cognitively healthy twins with demented co-twins (n=101 pairs) recalled less words than cognitively healthy twins with cognitively healthy co-twins (n=770 pairs) after adjusting for age, sex and education, B=-0.44, 95% C I (-0.73 to -0.14), p=0.003. The effect size was similar in MZ (n=31) twins (3.88 vs 4.29 words, B=-0.41, 95% C I (-0.96 to 0.13)) and DZ (n=66) twins (3.70 vs 4.17 words, B=-0.47, 95% C I (-0.84 to -0.10)). The heritability estimate of immediate recall (IR) was 0.37, 95% C I (0.21 to 0.43). Conclusions The results demonstrate that familial risk for dementia is reflected in the IR performance of cognitively healthy older persons. The finding of poorer IR performance in non-affected siblings compared with the general population, together with substantial heritability of IR, supports IR as a useful endophenotype for molecular genetic studies of dementia.Peer reviewe

Association of protein phosphatase PPM1G with alcohol use disorder and brain activity during behavioral control in a genome-wide methylation analysis

OBJECTIVE: The genetic component of alcohol use disorder is substantial, but monozygotic twin discordance indicates a role for nonheritable differences that could be mediated by epigenetics. Despite growing evidence associating epigenetics and psychiatric disorders, it is unclear how epigenetics, particularly DNA methylation, relate to brain function and behavior, including drinking behavior. METHOD: The authors carried out a genome-wide analysis of DNA methylation of 18 monozygotic twin pairs discordant for alcohol use disorder and validated differentially methylated regions. After validation, the authors characterized these differentially methylated regions using personality trait assessment and functional MRI in a sample of 499 adolescents. RESULTS: Hypermethylation in the 3'-protein-phosphatase-1G (PPM1G) gene locus was associated with alcohol use disorder. The authors found association of PPM1G hypermethylation with early escalation of alcohol use and increased impulsiveness. They also observed association of PPM1G hypermethylation with increased blood-oxygen-level-dependent response in the right subthalamic nucleus during an impulsiveness task. CONCLUSIONS: Overall, the authors provide first evidence for an epigenetic marker associated with alcohol consumption and its underlying neurobehavioral phenotype

Prevalence and correlates of dementia and mild cognitive impairment classified with different versions of the modified Telephone Interview for Cognitive Status (TICS-m)

Objectives The modified Telephone Interview for Cognitive Status (TICS-m) is an efficient and cost-effective screening instrument of dementia, but there is less support for its utility in the detection of mild cognitive impairment (MCI). We undertook a comprehensive evaluation of the utility of different TICS-m versions with or without an education-adjusted scoring method to classify dementia and MCI in a large population-based sample. Methods Cross-sectional assessment of cognition (TICS-m), depressive symptoms (CES-D), and apolipoprotein E (APOE) epsilon 4 status was performed on 1772 older adults (aged 71-78 y, education 5-16 y, 50% female) from the population-based older Finnish Twin Cohort. TICS-m classification methods with and without education adjustment were used to classify individuals with normal cognition, MCI, or dementia. Results The prevalence of dementia and MCI varied between education-adjusted (dementia = 3.7%, MCI = 9.3%) and unadjusted classifications (dementia = 8.5%-11%, MCI = 22.3%-41.3%). APOE epsilon 4 status was associated with dementia irrespective of education adjustment, but with MCI only when education adjustment was used. Regardless of the version, poorer continuous TICS-m scores were associated with higher age, lower education, more depressive symptoms, male sex, and being an APOE epsilon 4 carrier. Conclusions We showed that demographic factors, APOE epsilon 4 status, and depressive symptoms were similarly related to continuous TICS-m scores and dementia classifications with different versions. However, education-adjusted classification resulted in a lower prevalence of dementia and MCI and in a higher proportion of APOE epsilon 4 allele carriers among those identified as having MCI. Our results support the use of education-adjusted classification especially in the context of MCI.Peer reviewe

Accuracy of Imputation for Apolipoprotein E epsilon Alleles in Genome-Wide Genotyping Data

This diagnostic study evaluates the association of reference panels with imputation quality for 2 single-nucleotide polymorphisms located on the apolipoprotein E (APOE) gene.Non peer reviewe

Education as a moderator of middle-age cardiovascular risk factor-old-age cognition relationships : testing cognitive reserve hypothesis in epidemiological study

Background higher educational attainment and less midlife cardiovascular risk factors are related to better old-age cognition. Whether education moderates the association between cardiovascular risk factors and late-life cognition is not known. We studied if higher education provides resilience against the deteriorative effects of higher middle-age body mass index (BMI) and a combination of midlife cardiovascular risk factors on old-age cognition. Methods the study population is the older Finnish Twin Cohort (n = 4,051, mean age [standard deviation, SD] = 45.5 years [6.5]). Cardiovascular risk factors and education were studied at baseline with questionnaires in 1975, 1981 and/or 1990 (participation rates of 89, 84 and 77%, respectively). Cognition was evaluated with telephone interviews (participation rate 67%, mean age [SD] =73.4 [2.9] years, mean follow-up [SD] = 27.8 [6.0] years) in 1999-2017. We studied the main and interactive effects of education and BMI/dementia risk score on late-life cognition with linear regression analysis. The study design was formulated before the pre-defined analyses. Results years of education moderated the association between BMI with old-age cognition (among less educated persons, BMI-cognition association was stronger [B = -0.24 points per BMI unit, 95% CI -0.31, -0.18] than among more educated persons [B = -0.06 points per BMI unit, 95% CI -0.16, 0.03], P-interaction < 0.01). There was a similar moderating effect of education on dementia risk score consisting of cardiovascular risk factors (P < 0.001). Conclusions our results support the cognitive reserve hypothesis. Those with higher education may tolerate the deteriorative effects of midlife cardiovascular risk factors on old-age cognition better than those with lower education.Peer reviewe

Middle-age dementia risk scores and old-age cognition : a quasi-experimental population-based twin study with over 20-year follow-up

Background Middle-age risk scores predict cognitive impairment, but it is not known if these associations are evident when controlling for shared genetic and environmental factors. Using two risk scores, self-report educational-occupational score and Cardiovascular Risk Factors, Aging and Dementia (CAIDE), we investigated if twins with higher middle-age dementia risk have poorer old-age cognition compared with their co-twins with lower risk. Methods We used a population-based older Finnish Twin Cohort study with middle-age questionnaire data (n=15 169, mean age=52.0 years, SD=11.8) and old-age cognition measured via telephone interview (mean age=74.1, SD=4.1, n=4302). Between-family and within-family linear regression analyses were performed. Results In between-family analyses (N=2359), higher educational-occupational score was related to better cognition (B=0.76, 95% CI 0.69 to 0.83) and higher CAIDE score was associated with poorer cognition (B=-0.73, 95% CI -0.82 to -0.65). Within twin-pair differences in educational-occupational score were significantly related to within twin-pair differences in cognition in dizygotic (DZ) pairs (B=0.78, 95% CI 0.25 to 1.31; N=338) but not in monozygotic (MZ) pairs (B=0.12, 95% CI -0.44 to 0.68; N=221). Within twin-pair differences in CAIDE score were not related to within twin-pair differences in cognition: DZ B=-0.38 (95% CI -0.90 to 0.14, N=343) and MZ B=-0.05 (95% CI -0.59 to 0.49; N=226). Conclusion Middle-age dementia risk scores predicted old-age cognition, but within twin-pair analyses gave little support for associations independent of shared environmental and genetic factors. Understanding genetic underpinnings of risk score-cognition associations is important for early detection of dementia and designing intervention trials.Peer reviewe

Modifying the minimum criteria for diagnosing amnestic MCI to improve prediction of brain atrophy and progression to Alzheimer’s disease

Mild cognitive impairment (MCI) is a heterogeneous condition with variable outcomes. Improving diagnosis to increase the likelihood that MCI reliably reflects prodromal Alzheimer's Disease (AD) would be of great benefit for clinical practice and intervention trials. In 230 cognitively normal (CN) and 394 MCI individuals from the Alzheimer's Disease Neuroimaging Initiative, we studied whether an MCI diagnostic requirement of impairment on at least two episodic memory tests improves 3-year prediction of medial temporal lobe atrophy and progression to AD. Based on external age-adjusted norms for delayed free recall on the Rey Auditory Verbal Learning Test (AVLT), MCI participants were further classified as having normal (AVLT+, above -1 SD, n = 121) or impaired (AVLT -, -1 SD or below, n = 273) AVLT performance. CN, AVLT+, and AVLT- groups differed significantly on baseline brain (hippocampus, entorhinal cortex) and cerebrospinal fluid (amyloid, tau, p-tau) biomarkers, with the AVLT- group being most abnormal. The AVLT- group had significantly more medial temporal atrophy and a substantially higher AD progression rate than the AVLT+ group (51% vs. 16%, p <0.001). The AVLT+ group had similar medial temporal trajectories compared to CN individuals. Results were similar even when restricted to individuals with above average (based on the CN group mean) baseline medial temporal volume/thickness. Requiring impairment on at least two memory tests for MCI diagnosis can markedly improve prediction of medial temporal atrophy and conversion to AD, even in the absence of baseline medial temporal atrophy. This modification constitutes a practical and cost-effective approach for clinical and research settings.Peer reviewe