COGNITIVE IMPAIRMENT IN FAMILIES WITH PURE AUTOSOMAL-DOMINANT HEREDITARY SPASTIC PARAPARESIS

In the course of a study of a large family with pure autosomal dominan t hereditary spastic paraparesis (AD-HSP), mild cognitive impairment w as found in older family members. In order to determine if cognitive i mpairment occurred more frequently in families with pure AD-HSP than n ormally expected, a case control study of cognitive function in HSP wa s undertaken. Thirty-one patients, from 12 kindreds with pure AD-HSP, matched with 31 healthy control subjects for age, sex and years of edu cation, were assessed for evidence of cognitive impairment using the C ambridge Cognitive Examination (CAMCOG), Twenty unaffected siblings ma tched with twenty healthy control subjects were similarly assessed. Th e 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 (m ean 96.52/107, SD 5.52, 95% confidence interval 94.49-98.54) was signi ficantly reduced (P = 0.0003), There were also significant abnormaliti es in three out of the nine subsets including memory (P = 0.0002), lan guage comprehension (P = 0.0166) and language expression (P = 0.0025), The differences between the groups were due to cognitive impairment a ppearing after the age of 50 years in patients with AD-HSP; CAMCOG sco res before this age were similiar to control scores. There was also a minor nonsignificant difference in total CAMCOG score for the unaffect ed siblings (mean 93.7/107, SD 8.54, 95% cofidence interval 89.70-97.7 0) compared with the control group (mean 97.9/107, SD 4.61, 95% confid ence interval 95.7-100.1) (P < 0.02), This study demonstrates that mil d cognitive impairment develops after the age of 50 years in patients with pure AD-HSP and is further evidence of degeneration in other syst ems in this disorder.