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New findings indicate that genetics may not be the only underlying cause of young-onset dementia. Risk factors and risk markers for the disease, many of which are modifiable through lifestyle, were identified in a recent prospective UK Biobank study published in JAMA Neurology, including vitamin D deficiency, high C-reactive protein (CRP) levels, living with hearing loss, and social isolation.¹

While dementia is often perceived as a condition affecting older adults, rates of young-onset dementia, in which symptoms of dementia start before the age of 65 years, have been increasing globally.² A 2021 systematic review and meta-analysis estimates that nearly four million people age 30 to 64 are living with young-onset dementia globally. Subgroup analyses showed prevalence between men and women to be similar, whereas prevalence was lower in high-income countries compared with upper-middle-income and lower-middle income countries.² Although the prevalence of young-onset dementia is lower compared to the late-onset equivalent, the impact is particularly high, with symptoms affecting employment, social life, and familial responsibilities.¹

The 2023 observational study included 356,000 primarily white men and women (enrolled at age 40) without dementia diagnosis at baseline; baseline assessment occurred from 2006-2010, and participants were followed until 2021 or until they reached age 65.¹ Blood, urine, and saliva levels were measured along with weight and other health-related factors, and researchers compared these levels between groups who did and who did not develop early dementia.¹

Researchers evaluated a list of 39 potential risk factors, ranging from genetic predispositions to lifestyle and environmental influences, and identified 15 factors robustly associated with young-onset dementia.¹ Many similarities between the risk of late-onset and young-onset dementia were found, including alcohol abuse disorder (HR 2.39), carrying two APOE4 alleles (HR 1.87), diabetes (HR 1.65), depression (HR 3.25), heart disease (HR 1.61), and stroke (HR 2.07). Newly identified risk factors include social isolation (HR 1.53), hearing impairment (HR 1.56), orthostatic hypotension (HR 4.20), and low vitamin D levels HR (1.59). Having higher levels of C-reactive protein (HR 1.54) was also associated with a higher risk of young-onset dementia in women.¹

During eight years of follow up, the incidence rate of young-onset dementia was 16.8 per 100,000 person-years; 485 new cases of young-onset dementia were seen.¹ Incidence increased in five-year bands from ages 40 to 64 and was higher in men compared with women.¹

Multiple risk factors and risk markers for young-onset dementia have been investigated in two previous case-control studies and one retrospective cohort study.^1,3-5 Similar to the 2023 study results, stroke, depression, and alcohol use disorder were found to be associated with incident young-onset dementia. Additionally, these studies found associations with height, hypertension, dementia in the father, overall cognitive function, other drug use disorder, and neuroleptic use.¹

Further research is necessary to identify the underlying mechanisms of young-onset dementia, as scientists begin developing effective prevention strategies. Meanwhile, the clinical understanding of how nutrition and other lifestyle factors like intellectual challenge and exercise support cognition and optimal brain function continues to evolve.

Functional medicine is ideally suited to work with patients struggling with cognitive decline, especially in the early stages. Using the GOTOIT framework, clinicians identify unhealthy patterns and propose lifestyle modifications that are most beneficial to the patient’s current conditions and concerns. Treatments for patients with cognitive issues and those concerned about brain aging may include support of mitochondrial health and concurrent consideration of multiple lifestyle factors, including exercise, nutrition, intellectual challenge, sleep, and relationships.

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A Multimodal Lifestyle Approach for Cognitive Decline 

Inflammatory Bowel Disease & Dementia Risk 

Mediterranean Diet and Dementia – Is Diet the Path to Prevention? 

References

1. Hendriks S, Ranson JM, Peetoom K, et al. Risk factors for young-onset dementia in the UK Biobank. JAMA Neurol. Published online December 26, 2023. doi:10.1001/jamaneurol.2023.4929
2. Hendriks S, Peetoom K, Bakker C, et al. Global prevalence of young-onset dementia: a systematic review and meta-analysis. JAMA Neurol. 2021;78(9):1080-1090. doi:10.1001/jamaneurol.2021.2161
3. Cations M, Draper B, Low LF, et al. Non-genetic risk factors for degenerative and vascular young onset dementia: results from the INSPIRED and KGOW studies. J Alzheimers Dis. 2018;62(4):1747-1758. doi:10.3233/JAD-171027
4. Chen Y, Sillaire AR, Dallongeville J, et al. Low prevalence and clinical effect of vascular risk factors in early-onset Alzheimer’s disease. J Alzheimers Dis. 2017;60(3):1045-1054. doi:10.3233/JAD-170367
5. Nordström P, Nordström A, Eriksson M, Wahlund LO, Gustafson Y. Risk factors in late adolescence for young-onset dementia in men: a nationwide cohort study. JAMA Intern Med. 2013;173(17):1612-1618. doi:10.1001/jamainternmed.2013.9079