. Risk Factors for Young-Onset Dementia in the UK Biobank. JAMA Neurol. 2024 Feb 1;81(2):134-142. PubMed.

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  1. This study identified risk factors for young-onset dementia, including: lower formal education, lower socioeconomic status, carrying two apolipoprotein e4 alleles, no alcohol use, alcohol use disorder, social isolation, vitamin D deficiency, high C-reactive protein levels (women only), lower handgrip strength, hearing impairment, orthostatic hypotension, stroke, diabetes (men only), heart disease, and depression.

    The take-home message is that risk factors for young-onset dementia identified from the U.K. Biobank include many, but not all, of the same risk factors as those identified for older-onset, aka late-onset dementia. I can summarize in two words the most important thing to do to reduce your risk of dementia, whether you are young or old: Stay healthy!

    The biggest thing that surprised me were the risk factors that were missing: physical activity, diet, high blood pressure.

    To understand the risk factors, I think it is helpful to think about them in categories.

    There are risk factors that we know, or suspect, to actually cause dementia, either directly or indirectly. These include carrying two apolipoprotein e4 alleles, alcohol use disorder, social isolation, vitamin D deficiency, hearing impairment, stroke, diabetes, and heart disease.

    Other risk factors may not cause dementia but may be associated with less cognitive reserve, leading dementia symptoms to show up earlier. These include lower formal education and lower socioeconomic status.

    Some apparent risk factors may be attributable to “reverse causation.” In other words, the impending dementia may cause symptoms that, because they present before overt dementia, appear to be risk factors. These include: lower handgrip strength (a sign of frailty), no alcohol use (because once people develop memory loss they may stop drinking, also known as the “healthy drinker effect”), and depression (because many people get sad when they have trouble remembering or when they are worried about having dementia).

    Lastly, there are risk factors that could be either a contributing cause or a result of the impending dementia. These include high C-reactive protein (a sign of inflammation) and orthostatic hypotension (which can lead to brain damage and dementia but can also be a result of some types of dementia).

    Prior studies also found the following risk factors associated with young-onset dementia: stroke, depression, alcohol use disorder, vitamin D deficiency, and social isolation. There were also some risk factors found in prior studies not found in this study: height, hypertension, dementia in the father, overall cognitive function, drug use disorder, and neuroleptic use (medication used to treat agitation or psychosis).

    View all comments by Andrew E. Budson

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Mutations

  1. APOE C130R (ApoE4)