Elsevier

Neurobiology of Aging

Volume 32, Issue 6, June 2011, Pages 1159.e1-1159.e5
Neurobiology of Aging

The fat mass and obesity gene is linked to reduced verbal fluency in overweight and obese elderly men

https://doi.org/10.1016/j.neurobiolaging.2011.02.006Get rights and content

Abstract

Humans carrying the prevalent rs9939609 A allele of the fat mass and obesity-associated (FTO) gene are more susceptible to developing obesity than noncarries. Recently, polymorphisms in the FTO gene of elderly subjects have also been linked to a reduced volume in the frontal lobe as well as increased risk for incident Alzheimer disease. However, so far there is no evidence directly linking the FTO gene to functional cognitive processes. Here we examined whether the FTO rs9939609 A allele is associated with verbal fluency performance in 355 elderly men at the age of 82 years who have no clinically apparent cognitive impairment. Retrieval of verbal memory is a good surrogate measure reflecting frontal lobe functioning. Here we found that obese and overweight but not normal weight FTO A allele carriers showed a lower performance on verbal fluency than non-carriers (homozygous for rs9939609 T allele). This effect was not observed for a measure of general cognitive performance (i.e., Mini-Mental State Examination score), thereby indicating that the FTO gene primarily affects frontal lobe-dependent cognitive processes in elderly men.

Introduction

Population-based studies have shown that subjects carrying at least 1 copy of the fat mass and obesity-associated (FTO) rs9939609 A allele have a higher risk for being overweight and obese than homozygous FTO rs9939609 T allele subjects (Dina et al., 2010). Furthermore, recent neuroimaging studies revealed that FTO polymorphisms are associated with a reduction in frontal lobe volume (Ho et al., 2010) and increased risk for incident Alzheimer disease (Keller et al., 2010). This has prompted some clinical researchers to conjecture whether one of the most important obesity genes is linked to central nervous system processes (Bertram and Heekeren, 2010). Verbal fluency represents a distinct dimension of memory which crucially relies on an intact frontal lobe function (Martin et al., 1994). From this premise we examined the influence of the FTO gene on the Mini-Mental State Examination (MMSE) score, a cognitive measure reflecting global rather than brain region-specific cognitive functioning in humans (Folstein et al., 1975). Furthermore, we tested the hypothesis that the FTO A allele is associated with impaired verbal fluency in a large data set involving 355 old men at the age of 82 years from the Uppsala Longitudinal Study of Adult Men (ULSAM).

Section snippets

Study population and data recording

Descriptive data of the study population are shown in Table 1. Data derived from the ULSAM project, a population-based prospective cohort study that initially included 2322 Caucasian men who were born between 1920 and 1924 and lived in Uppsala, Sweden (www.pubcare.uu.se/ULSAM). After their inclusion between 1970 and 1974, subjects were followed up at intervals of 5 to 10 years. Assessment of verbal fluency, results of which are reported here, took place at the age of 82 years and performed in a

Verbal fluency but not general cognitive performance is reduced in overweight/obese carriers of the FTO A allele

The FTO A allele frequency was 39% in our cohort, which corresponds to the prevalence found in comparable population based studies (e.g., Dina et al., 2010). Overall, the FTO A allele was not significantly associated with altered performance on the verbal fluency performance (β = −0.034, standard error [SE] = 0.030; 95% confidence interval [CI], −0.091 to 0.022; p = 0.235, adjusted for BMI, age, educational status, hypertension status, T2DM status, and apolipoprotein E genotype; Fig. 1A).

Discussion

Our data indicate that the FTO rs9939609 A allele is associated with diminished performance on a verbal fluency task in overweight and obese but not in lean elderly men. This finding suggests that the FTO gene exerts a modulating influence on human cognition that is dependent on an individual's body weight.

Previous epidemiological studies have consistently shown an association between increased body weight and mild to moderate impairments of cognitive functions in nondemented subjects (Cohen,

Disclosure statement

All authors had full access to all data in the study and take responsibility for the integrity and accuracy of the data analysis. The authors have no conflicts to disclose.

The study was approved by the Ethics committee of Uppsala University, Faculty of Medicine. All participants gave their written informed consent.

Acknowledgements

The study was funded by Swedish Research Council, Novo Nordisk Foundation, Wallenberg Consortium North, Swedish Brain Fund, Alzheimerfonden, APOPIS, Stiftelsen Gamla Tjänarinnor, Capios Forskningsstiftelse, Erik, Karin och Gösta Selanders stiftelse, and Swedish Lions Research Foundation. The funding sources had no input in the design and conduct of this study; in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.

References (19)

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