LoHD is defined as HD diagnosed in individuals showing the first motor symptoms at ≥60 years of age. LoHD represents 4?11% of individuals with HD, yet the prognosis and natural history of LoHD remain unclear.

Demographics, motor function, comorbidities and longitudinal disease progression were summarized for North American participants in the Enroll-HD (NCT01574053) study with clinically manifest LoHD and a documented cytosine adenine guanine (CAG) repeat size (n=431). Data from North American participants with adult-onset HD (diagnosed with manifest HD between 21 and 59 years of age [n=1,708]) and North American age-matched participants who did not carry the HD expansion mutation (controls [n=361]) were included.

The prevalence of LoHD was 19.2%; 93.5% were Caucasian. Mean age at enrollment was 69.0 years and mean CAG repeat size was 40.9; 85.6% had 40–42 CAG repeats. Incidences of comorbidities, including psychiatric, ophthalmologic and neurologic, were statistically higher in the LoHD group than in controls. The most common cancers reported in LoHD group were skin, breast and prostate cancer. In individuals with ≥1 year of follow-up in the LoHD group (n=241), scores on the composite Unified HD Rating Scale (cUHDRS) worsened by 0.84 points versus 0.82 points in the adult-onset group. LoHD participants had a decline in gait (28.1%) and walking ability (17.5%) as measured by the UHDRS Motor Assessment and UHDRS Functional Assessment Independence Scale, respectively. Large CAG-age product (CAP) score, tetrabenazine use, antipsychotics use, presence of care provider at enrollment visit and cognitive impairment were associated with an increased rate of progression over 1 year in people with LoHD.