Evidence of presymptomatic cognitive decline in Huntington's disease

Abstract

Asymptomatic persons at risk for Huntington's disease (HD) (N = 28) were assessed with neuropsychological, psychiatric, and neurologic tests while undergoing genetic linkage studies to determine their probability of carrying the HD gene. Those participants who were subsequently identified as probable gene carriers did not differ on neurologic or psychiatric examination from those subsequently identified as probable noncarriers. Neuropsychological data are presented for a subset of participants free of other conditions (such as alcoholism) putting them at risk for cognitive deficits. Among these subjects, probable gene carriers were inferior to probable noncarriers on the neuropsychological battery as a whole and on several individual tests involving learning and memory. The results suggest the presence of cognitive decline prior to identifiable motor impairments in HD.

Presymptomatic Signs in Healthy CJD Mutation Carriers

“…At-risk subjects may respond with anxiety to the experience of subtle cognitive deterioration (although they do not report it). A similar explanation has recently been offered for clinically healthy subjects at risk for HD [10,14] . The fi rst suggestion, therefore, is that in CJD, the cognitive defi cits are the primary consequences of the genetic mutation, while stress and anxiety are secondary responses.…”

“…Subjects' demographic information (age and education) and general cognitive potential (MMSE and WAIS-R) (a, for the subject population generally; b, separating between young and elder subjects). There were no signifi cant statistical differences between groups in any of the demographic parameters a Controls (14) Carriers (13) (16) controls (5) carriers (6) t-test sig. controls (9) carriers (7) cantly lower in all cognitive parameters (post-hoc Scheffé, p !…”

“…The most noticeable cognitive defi cits in our at-risk subjects were in the tasks of object naming and recognition. The very fact of presymptomatic defi cits is not surprising since presymptomatic cognitive defi cits were shown in other dementias, e.g., HD and AD [1,10,14,18,25,56,61] . Our results, however, are theoretically problematic, for if the observed defi cits originate in extended arousal levels, which is the more likely explanation, then they should be diffuse and span a wide range of cognitive functions and perhaps even be of a psychiatric nature [41] .…”

“…Recent studies demonstrated neuropsychological presymptoms in other kinds of dementia such as AD and HD [1,10,14,16,18,19,25,51,56,61] but, thus far, no research has evaluated either subjects at * Signifi cance is related to the Mann-Whitney t-test for non-parametric independent samples, comparing between the two elder groups (carriers and controls). 1 The Auditory Verbal Learning Test (AVLT) included 15 words that were auditory presented at 5 times (each named a trial), and subjects were asked (at each trial) to recall as many words as they could remember.…”

WAIS-R Features of Preclinical Huntington’s Disease: Implications for Early Detection

“…Several earlier investigations have used portions of the Wechsler scales [40] to measure cognitive functioning in asymptomatic carriers [12,18,19,23,43,48,51] . A very early study by Lyle and Gottesman [37] reported a followup of 88 at-risk subjects who had been examined 15-20 years previously, where large differences in Wechsler IQs were observed between 28 persons who developed HD and 60 persons who did not.…”