Early-Onset Vascular Dementia in a 43-Year-Old Man with Accelerated Atherosclerotic Disease, Elevated Lipoprotein (a), and a Missense DNAJC5 Variant with Potential Association to Adult-Onset Ceroid Lipofuscinosis

Early-onset dementia is defined as dementia occurring prior to the age of 65. Given its impact on physical, mental, and socioeconomic well-being, it is crucial to identify modifiable risk factors. Here, we report a 43-year-old man with early-onset dementia associated with elevated lipoprotein (a) and a missense variant in the DNAJC5 gene. He presented to the hospital with memory loss and multiple cerebrovascular infarcts. Eight months prior, an MRI revealed small acute and subacute infarcts involving the left PCA for which he was treated with antiplatelet agents and a statin. Three months later, he was readmitted for progressive memory loss. CT imaging showed evolving and new infarcts compared to prior scans. A cardiac echocardiogram excluded thrombus and PFO, and he was diagnosed with early vascular dementia. He was readmitted again 5 months later with additional evaluation revealing multifocal moderate to severe stenosis and irregularities involving the bilateral ICA and bilateral PCAs. MRI showed more pronounced infarcts compared to a previous MRI as well as new infarcts. CSF studies, VDRL, RF, ANA, ANCA, homocysteine, and MMA levels were normal. Lipoprotein (a) was found to be markedly elevated, and genetic testing revealed a missense variant of the DNAJC5 gene, the mutation of which is associated with ceroid lipofuscinosis. In conclusion, in patients with early-onset dementia and evidence of accelerated atherosclerosis, it is reasonable to measure Lp(a) and consider testing for variants in genes such as DNAJC5 and others, particularly when disease severity appears unexplained by known risk factors or circumstances.