Psychosocial Risk Factors for Alzheimer’s Disease in Patients with Down Syndrome and Their Association with Brain Changes: A Narrative Review

Abstract

Several recent epidemiological studies attempted to identify risk factors for Alzheimer’s disease. Age, family history, genetic factors (APOE genotype, trisomy 21), physical activity, and a low level of schooling are significant risk factors. In this review, we summarize the known psychosocial risk factors for the development of Alzheimer’s disease in patients with Down syndrome and their association with neuroanatomical changes in the brains of people with Down syndrome. We completed a comprehensive review of the literature on PubMed, Google Scholar, and Web of Science about psychosocial risk factors for Alzheimer’s disease, for Alzheimer’s disease in Down syndrome, and Alzheimer’s disease in Down syndrome and their association with neuroanatomical changes in the brains of people with Down syndrome. Alzheimer’s disease causes early pathological changes in individuals with Down syndrome, especially in the hippocampus and corpus callosum. People with Down syndrome living with dementia showed reduced volumes of brain areas affected by Alzheimer’s disease as the hippocampus and corpus callosum in association with cognitive decline. These changes occur with increasing age, and the presence or absence of psychosocial risk factors impacts the degree of cognitive function. Correlating Alzheimer’s disease biomarkers in Down syndrome and cognitive function scores while considering the effect of psychosocial risk factors helps us identify the mechanisms leading to Alzheimer’s disease at an early age. Also, this approach enables us to create more sensitive and relevant clinical, memory, and reasoning assessments for people with Down syndrome.

Correlating MRI-Based Brain Volumetry and Cognitive Assessment in People with Down Syndrome

“…Our study confirmed the link between hippocampal volume reduction and deficits in language functions and working memory (see figure 20), which has been reported widely by previous studies (Raz, Torres et al 1995, Krasuski, Alexander et al 2002, Pennington, Moon et al 2003. These findings reflect the role of the hippocampus as an essential biomarker for AD and one of the regions severely affected by the neuropathological changes of AD (Aylward, Li et al 1999, Hamadelseed, Elkhidir et al 2022. We found no significant correlation between age and hippocampal volume.…”

“…Our study results confirmed the association between temporal lobe volume reduction and deficits in working memory (see figure 20). This finding ensures the temporal lobe's role in memory function (Galaburda and Schmitt 2003, Pennington, Moon et al 2003, Vicari 2006, Menghini, Costanzo et al 2011, Mullins, Daly et al 2013, Hamadelseed, Elkhidir et al 2022) (see figure 9). Our results could not confirm the involvement of the temporal lobe in language deficits.…”

“…By studying these areas of interest and comparing their volumes with the psychological results, we can approach language and memory problems in people with DS and provide a basis for further research, including early interventions. Furthermore, studying the early stage of AD as DS can provide a suitable pattern for understanding AD pathology and clinical features at an early age (Mann 1988, Delabar, Blouin et al 1990, Hartley, Blumenthal et al 2015, Lott and Head 2019, Hamadelseed, Elkhidir et al 2022. In general, we will compare the imaging data on brain areas between DS participants and normal controls.…”

Quality of life in adults with Down syndrome: A mixed methods systematic review

“…Down syndrome (DS) is the most common genetic cause of intellectual and developmental disability (IDD) resulting from the presence of an extra copy of chromosome 21 [ 1 , 2 ]. Globally, there are approximately 1:1000 to 1:1100 live births of people with DS [ 3 ].…”

Correlating MRI‐based brain volumetry and cognitive assessment in people with Down syndrome

“…Using a developmental approach, a better understanding of the developing brain with DS will illuminate important neurological principles of DS in children and shed light on the foundations of adult phenotypes, particularly the increased risk of early Alzheimer's disease (AD) (Lee et al., 2015; Zigman & Lott, 2007). Furthermore, investigating DS helps us study the early stage of AD, as DS can provide a suitable pattern for understanding AD pathology and clinical features at an early age (Delabar et al., 1990; Hamadelseed et al., 2022; Hartley et al., 2015; Lott & Head, 2019; Mann, 1988).…”