Biopsychosocial risk factors for Alzheimer's disease and related dementias in UK immigrants from the Middle East and North Africa (MENA)

Abstract

The Middle East and North Africa (MENA) region represents the area of greatest projected growth in instances of Alzheimer's disease and related dementias (ADRDs) globally, yet, it remains virtually uncharacterized in health studies of aging and ADRDs. The UK Biobank is one of the largest and well characterized datasets of aging immigrants in the UK, offering an unprecedented opportunity to identify risk factors for ADRDs in individuals from MENA regions. Here we used the UK Biobank to compare sociodemographic, disease, lifestyle, genetic, and neuroimaging risk factors for ADRDs among UK immigrants from MENA countries (N=3,552) with two other large immigrant populations from Germany (N=1,097) and India (N=2,935), as well as a genetically British white control group born outside the UK (N=1,925). MENA immigrants exhibited a distinct and adverse risk profile characterized by greater socioeconomic deprivation, higher exposure to air pollution, poorer diet quality, lower physical activity, worse sleep, and higher smoking prevalence compared to European immigrant groups. The same trends were observed when comparing MENA to Indian immigrants, though these differences were less pronounced. These behavioral and environmental risk factors were accompanied by markedly higher rates of obesity, diabetes, hypertension, and other cardiometabolic conditions. Despite this substantial phenotypic burden, MENA participants carried a lower frequency of established AD genetic risk variants, including ApoE4, highlighting a discordance between genetic risk and observed disease related vulnerability. Neuroimaging analyses revealed lower hippocampal volume in MENA and Indian participants relative to European groups despite younger average age, consistent with early limbic vulnerability associated with metabolic and inflammatory stress. Overall, our results indicate that dementia risk in MENA populations is driven by a multidimensional framework of metabolic, systemic, and social environmental exposures that may shape vulnerability independently of canonical European-derived genetic risk factors. These findings highlight the urgent need for ancestry- and context-specific frameworks to support equitable dementia prevention and avoid under-predicting risk in underrepresented populations.