, 2005, Pannacciulli et al , 2006, Taki et al , 2008 and Raji et

, 2005, Pannacciulli et al., 2006, Taki et al., 2008 and Raji et al., 2010). Greater BMI is also found to correlate with Trametinib in vivo decreased neuronal viability of grey matter in temporal lobes of middle-aged adults, and neuronal and/or myelin metabolic abnormalities in grey and white matter (Gazdzinski et al., 2008, Gazdzinski et al., 2010 and Mueller et al., 2011). Thus, the reduction in regional brain volumes in obese individuals could reflect loss of neurons. It is well known that large hippocampal size is closely linked with good cognitive

function and memory (Stewart et al., 2005), and frontal brain regions are necessary for intact executive functions (Alvarez and Emory, 2006). Thus, whilst direct evidence is lacking, it is conceivable

that atrophy of these brain regions contributes to poor cognitive performance in obese individuals. The majority of studies examining associations between obesity and cognitive health/brain structure either do not include females or study males or females in isolation. Furthermore, findings from studies where potential sex-dependent differences have been examined are mixed. For example, in the Framingham Heart Study it was found that higher BMI was associated with poorer cognitive performance in middle-aged men but not women, with a significant interaction between obesity and sex (Elias et al., 2003 and Elias et al., 2005). Similarly, Kanaya et al. reported higher Lumacaftor chemical structure total fat mass, abdominal fat, BMI, and waist circumference, are associated with worsening of cognitive function in elderly men at follow up seven years later, whereas women of similar age have a trend towards inverse Coproporphyrinogen III oxidase associations between these obesity indices and cognitive function (Kanaya et al., 2009). In contrast, Cournot et al. found no sex-dependent differences in the adverse effects of obesity (BMI) on cognitive performance in either young or middle-aged individuals (Cournot et al., 2006). There is also controversy in the literature about whether sex influences the association between obesity and alterations in brain structure. For example, a study found

an association between BMI and cerebral volume loss in men but not in women (Taki et al., 2008), whereas two separate studies showed an association between BMI and brain atrophy in women (Gustafson et al., 2004 and Raji et al., 2010). Gazdzinski et al. found virtually identical relationships between BMI and markers of myelin metabolic abnormalities in males and females (Gazdzinski et al., 2008). In contrast, another study found an association between BMI and markers of myelin degeneration only in women (Mueller et al., 2011). It is clear therefore that more research is required to fully determine whether sex influences obesity-related function and structural brain changes. The hypothalamic–pituitary-adrenal (HPA) axis plays an important role in many brain functions including cognitive function. Moreover, as discussed in Section 6.

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