Cognitive impairment in families with pure autosomal dominant hereditary spastic paraparesis

In the course of a study of a large family with pure autosomal dominant hereditary spastic paraparesis (AD-HSP), mild cognitive impairment was found in older family members. In order to determine if cognitive impairment occurred more frequently in families with pure AD-HSP than normally expected, a case control study of cognitive function in HSP was undertaken. Thirty-one patients, from 12 kindreds with pure AD-HSP, matched with 31 healthy control subjects for age, sex and years of education, were assessed for evidence of cognitive impairment using the Cambridge Cognitive Examination (CAMCOG). Twenty unaffected siblings matched with twenty healthy control subjects were similarly assessed. The total CAMCOG score in the affected group (mean 89.26/107, SD 11.08, 95% confidence interval 85.2-94.49) compared with the control group (mean 96.52/107, SD 5.52, 95% confidence interval 94.49-98.54) was significantly reduced (P = 0.0003). There were also significant abnormalities in three out of the nine subsets including memory (P = 0.0002), language comprehension (P = 0.0166) and language expression (P = 0.0025). The differences between the groups were due to cognitive impairment appearing after the age of 50 years in patients with AD-HSP; CAMCOG scores before this age were similar to control scores. There was also a minor non-significant difference in total CAMCOG score for the unaffected siblings (mean 93.7/107, SD 8.54, 95% confidence interval 89.70-97.70) compared with the control group (mean 97.9/107, SD 4.61, 95% confidence interval 95.7-100.1) (P < 0.02). This study demonstrates that mild cognitive impairment develops after the age of 50 years in patients with pure AD-HSP and is further evidence of degeneration in other systems in this disorder.