![]() Mortimer et al., 2012 conducted a small randomized controlled trial (RCT) with older adults and found increased total brain volumes and cognitive function in participants after a social interaction intervention compared to a non-intervention control group. Furthermore, it suggested that white matter changes mediated the positive association between social activities and perceptual speed ( Köhncke et al., 2016). In a longitudinal study using a small sample of 70 participants (37 at follow-up) > 80 years old, microstructural deteriorations and a larger total white matter hyperintensity volume correlated with decreases in predominantly social activities ( Köhncke et al., 2016). Some studies have linked low social connection to an elevated ‘brain age’ gap estimate ( de Lange et al., 2021), changes in microstructural ( Molesworth et al., 2015 Spreng et al., 2020 Tian et al., 2014), and volumetric measures in brain regions including the hippocampus and the prefrontal cortex ( Blumen and Verghese, 2019 Cotton et al., 2020 Düzel et al., 2019 James et al., 2012 Schurz et al., 2021 Shen et al., 2022 Spreng et al., 2020 Taebi et al., 2020) however, these cross-sectional designs render conclusions about causality difficult. Still, the link between brain structure and social connection, the umbrella term encompassing social isolation, social support, and loneliness, has not received much attention ( Wassenaar et al., 2019). Thus, brain magnetic resonance imaging (MRI) can be a potent dementia-risk indicator ( Wang et al., 2019), might offer pivotal guidance to identify patients for intensive dementia prevention ( Ten Kate et al., 2018), and serve as secondary outcome for intervention trials ( Stephen et al., 2019). Neuroimaging correlates of these brain changes have been observed multiple years prior to symptom onset in autosomal-dominant dementia ( Gordon et al., 2018) and can already be detected in cognitively healthy persons using neuroimaging ( Ewers et al., 2011 Jack et al., 2013). Risk factors of later dementia development often affect the structural brain changes dementia is characterized by: vascular degeneration, amyloid plaques, tau fibrillary tangles, neural degeneration, and grey matter loss. This is almost as many as to obesity, hypertension, and diabetes combined ( Livingston et al., 2020). calculated population-attributable fractions for risk factors for dementia and concluded that 3.5% of cases could be attributed to social isolation. Assuming causal relationships, Livingston et al. Systematic reviews and meta-analyses have concluded that social isolation, the objective lack of social contact, is such a risk factor for dementia ( Kuiper et al., 2015 Penninkilampi et al., 2018) and its main feature cognitive decline ( Evans et al., 2019 Kuiper et al., 2016). ![]() Henceforth, prevention is of cardinal importance and potentially modifiable risk factors are our most promising target ( Livingston et al., 2020). ![]() Research on pharmacological interventions targeting dementia pathogenesis has not yielded any result with a clear clinical benefit yet ( Knopman et al., 2021), and available drugs targeting cognitive symptoms offer at most a minor alleviation ( Knight et al., 2018). Already now, dementia’s global annual costs exceed one trillion US dollars ( Prince et al., 2015), and its detrimental effects on the lives of the afflicted make it a major contributor to the world’s burden of disease ( Vos et al., 2020). In just 20 years, this number will likely double. ![]() Over 50 million humans suffer from dementia today. ![]()
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