How is the brain affected by metabolically healthy or unhealthy obesity in adulthood and elderly? A narrative review of neuroimaging and neurocognitive findings

Antonietta Pepe¹Asieh Soltani^2,3Francesca Bracone²Augusto Di Castelnuovo²Maria Loreto Munoz Venegas²Chiara Cerletti²Donati Maria Benedetta²Giovanni De Gaetano²Licia Iacoviello^1,2*Alessandro Gialluisi^1,2*

• ¹Department of Medicine and Surgery, LUM University "Giuseppe Degennaro", Casamassima, Italy
• ²Research Unit of Epidemiology and Prevention, IRCCS NEUROMED, Pozzilli, Italy
• ³Ozhan pharm &tech co, Technology incubator of drug manufacturing, Tehran University of Medical Sciences, Teheran, Iran

The global aging of the population, coupled with an increasing prevalence of sedentary lifestyle and overnutrition, is fueling an alarming rise in the worldwide obesity rates. Besides its well-known bodily consequences, obesity is increasingly recognized emerging as an important risk factor for cognitive impairment, dementia, mood disorders, and emotional distress, suggesting a possible involvement role of excessive body fatadiposity in the pathogenesis of both neurodegeneration and neuropsychiatric diseases. Despite the growing research interest, the pathophysiological mechanisms linking obesity to brain health are stillremain poorly understood. Specifically,More particularly, it is unclear whether the neuroanatomical, neurofunctional, and neurocognitive correlates of late-life obesity are directly imputable to either the excessive body fat accumulation or physiological age-related neurodegeneration, or if they are mediated by possible cardio-metabolic comorbidities which are common chronic conditions among the elderlyies. We collectedThis narrative review synthesizes evidence on structural neuroimaging (MRI) and neurocognitive findings in both the adult life span and elderlyacross adulthood and late life, with a focusfocusing on the metabolically healthy obese individuals, a sub-group of the obese population maintaining a favorable cardio-metabolic health profile. Direct studies comparing on metabolically healthy obesity often show report inconclusive evidence for the effect of obesity on neuroanatomical This is a provisional file, not the final typeset article impairments or cognitive functions, and when the effects are present, they are much less pronounced compared to those observed in metabolically unhealthy individuals. Yet, many indirect studies reporting the effects of obesity after controlling for cardio-metabolic conditions point to thesuggest that obesity per se is associated with impact of obesity on brain atrophy, and loss ofreduced white matter integrity, and alterations in reward-homeostatic-control networks. In conclusion, current evidence indicates that metabolically healthy obesity might not be entirely benign for brain health. More longitudinal multimodal imaging studies, with better characterization of both obesity and metabolic phenotypes, areand therefore warranted their to clarify trajectories and causal pathwaysy over time are warranted.