Obesity has reached epidemic proportions, motivating research into the underlying mechanisms. Olfaction is a powerful mediator of food consumption, and obesity has been associated with altered olfactory sensitivity. The current study used an event-related functional magnetic resonance imaging (fMRI) to examine the central processing of odor in humans to gain insight into the effect of the body mass index (BMI) on the neural processes involved in rating the pleasantness of a food odor during a hunger state and in a satiety state. We hypothesized that, during the hedonic evaluation of food odor, BMI would be associated with differences in brain activation within olfactory and higher order processing areas important for perception, reward, and memory. We report novel findings of a dissociation between the relationship between BMI and activation in reward areas and in olfactory and odor memory areas, i.e., activation in reward areas decreased as BMI increased, whereas activation in primary olfactory and memory regions increased as BMI increased. A greater BMI is associated with decreased activation in the reward and frontal regions, supporting a blunted reward response in obesity. These findings have important potential implications for decision making, response inhibition, and reward-based behaviors that may play key roles as causal and maintenance factors in obesity. In contrast, a greater BMI is associated with an increased activation in the primary olfactory and memory areas, which was observed during a hunger state. These results raise the speculative hypothesis that high BMI may be associated with hyperactivation in the olfactory and memory areas, and that over time, the resulting excitotoxic effects may contribute to neurodegenerative changes in these areas.

Background: Early biomarkers of prodromal Alzheimer’s disease (AD) are critical both to initiate interventions and to choose participants for clinical trials. Odor threshold, odor identification and odor familiarity are impaired in AD. Methods: We investigated the relative abilities of standard screening (MMSE) and olfactory measures to predict transitions from cognitively normal (CN) to mild cognitive impairment (MCI), from CN to AD, and MCI to AD. The archival sample of 497, from the UCSD ADRC, included participants who were CN, MCI, AD and converters to MCI or AD. Apoe ε4 status, a genetic risk factor, was available for 256 participants, 132 were ε4 carriers. A receiver operating characteristic curve (ROC) curve plots the trade-off between sensitivity and specificity. Area under the ROC curve (AUC) was used to determine diagnostic accuracy. Results: Different measures were better predictors at specific stages of disease risk; e.g., odor familiarity, odor identification and the combination showed higher predictive value for converting from MCI to AD in ε4 carriers than the MMSE. Combining odor familiarity and odor identification produced an AUC of 1.0 in ε4 carriers, MMSE alone was 0.58. Conclusions: Olfactory biomarkers show real promise as non-invasive indicators of prodromal AD. The results support the value of combining olfactory measures in assessment of risk for conversion to MCI and to AD.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory impairment and the presence of amyloid plaques and neurofibrillary tangles. The associated neuropathology originates in brain areas responsible for olfaction

Metabolic Syndrome (MetS) is associated with increased rates of mortality and increased risk for developing dementia. Changes in brain structure and cognitive functioning have been reported within the literature. However, research examining cognitive performance in individuals with MetS is limited, inconclusive, and focuses primarily on older cohorts. As such, the effect of MetS on cognitive functioning earlier in the lifespan is unclear. This study aimed to investigate cognitive performance in young, middle-aged, and older adults with multiple metabolic and vascular risk factors in a sample of community dwelling participants (N = 128). Participants were administered a comprehensive neuropsychological battery and self-report measures. As expected, older adults performed more poorly than young and middle-aged adults across most assessments. Relative to controls, individuals with MetS reported greater hunger and disinhibited eating. MetS participants performed more poorly on Color-Word Interference: Inhibition. Additionally, when weight was accounted for, there was a significant relationship between MetS and select executive functioning tasks in middle-aged adults. These findings suggest that aspects of executive functioning may be impaired in MetS and could be further impacted by excess weight in middle-age. Future studies aimed at investigating potential causal relationships between metabolic and vascular risk factors, disinhibited eating, and executive dysfunction may provide insight into effective intervention targets to prevent MetS.