Cognitive Improvement After Multi-Domain Lifestyle Interventions in an APOE ɛ4 Homozygous Carrier with Mild Cognitive Impairment: A Case Report and Literature Review

Abstract

Alzheimer's disease (AD) is a degenerative disease of the central nervous system with insidious onset and chronic progression. The pathogenesis of AD is complex, which is currently considered to be the result of the interaction between genetic and environmental factors. The APOE ɛ4 is the strongest genetic risk factor for sporadic AD and a risk factor for progression from mild cognitive impairment (MCI) to AD. So far, no effective drugs have been found for the progression of MCI. However, the effects of nonpharmacological interventions such as nutrition, cognitive, and physical exercises on early AD have received increasing attention. We followed up cognitive assessment scales, Aβ-PET and MRI examination of a patient with MCI for 4 years, who carried APOE ɛ4 homozygous with a clear family history. After 4 years of multi-domain lifestyle interventions including nutrition, socialization, and physical exercises, the patient's cognitive function, especially memory function, improved significantly. Intracerebral amyloid deposition was decreased, and hippocampal atrophy improved. Based on this case, this study reviewed and discussed the interaction of APOE ɛ4 with the environment in AD research in recent years, as well as the impact and mechanisms of non-pharmaceutical multi-domain lifestyle interventions on MCI or early AD. Both the literature review and this case showed that multi-domain lifestyle interventions may reduce the risk of disease progression by reducing Aβ deposition in the brain and other different pathologic mechanisms, which offers promise in brain amyloid-positivity or APOE ɛ4 carriers.

Keywords: APOE; Alzheimer’s disease; diet; genetic risk effect; mild cognitive impairment; nutrition; physical activities; social contacts.