Identification of Subtle Verbal Memory Deficits in Premanifest Huntington Disease Using the California Verbal Learning Test

Abstract

Background: Verbal memory impairment in individuals with Huntington disease (HD) is well-documented; however, the nature and extent of verbal memory impairment in individuals with premanifest HD (pre-HD) are less understood. Objective: To evaluate verbal memory function in individuals with pre-HD by comparing their performance on the California Verbal Learning Test to that of individuals with a clinical diagnosis of HD and that of a demographically similar group of adults with no family history of, or genetic risk for, HD, thereby reducing possible complications of psychiatric difficulties commonly experienced by individuals who are at risk for HD but are gene negative. Methods: Participant groups included 77 adults with a diagnosis of HD, 23 premanifest gene carriers for HD (pre-HD), and 54 demographically similar, healthy adults. The California Verbal Learning Test—Second Edition (CVLT–II) was used to evaluate the participants’ immediate and delayed recall, recognition, learning characteristics, errors, and memory retention. Results: The pre-HD group performed significantly worse than the healthy group, yet significantly better than the HD group, on Short and Long Delay Recall (Free and Cued) and Recognition Discriminability. On Total Immediate Recall, Learning Slope, Semantic Clustering, and Intrusions, the pre-HD group performed similarly to the healthy group and significantly better than the HD group. None of the groups differed in their performance on Repetitions and a measure of retention. Conclusions: Subtle memory deficits can be observed during the premanifest stage of HD with use of a subset of indices from the CVLT–II.

Using the LASSI-L to Detect Robust Interference Effects in Premanifest Huntington Disease

“…However, our results suggest that by allowing for the recall of any item from either learned list (A or B), the LASSI-L paradigm enhanced the combined effects of both proactive and retroactive interference on the final Delayed Recall section. This overall effect may have contributed to the larger effect size that was recorded on the Delayed Free Recall section in our study (d = 1.652, P ≤ 0.001) compared with the effect that was reported for Long Delay Free Recall on the CVLT-II in a similar preHD population (d = 0.40, P = 0.05) (Holden et al, 2020). Performance on the Interference sections (PSI and RSI) of the LASSI-L was not significantly correlated with performance on the Stroop Word Reading subtest (the only other neuropsychological test that survived multiple comparisons in our battery) (r = 0.257, P = 0.397).…”

“…Each test has relative advantages: The CVLT allows measures of learning strategies (eg, semantic clustering and serial order); the LASSI–L has robust measures of interference. Regardless, our results provide further evidence that verbal learning tests are sensitive to early cognitive changes in individuals with preHD, and they should be incorporated with greater frequency in the assessment and monitoring of this specific population (Holden et al, 2020).…”

“…Deficits in source memory in individuals with manifest HD have been detected by the Rey Auditory Verbal Learning Test (Butters et al, 1985) and the California Verbal Learning Test I (CVLT-I; Delis et al, 1991), and intrusion errors have been detected by the CVLT-3 (Graves et al, 2019) and CVLT-II (Holden et al, 2020). Difficulties with the rate of improvement across trials, increased perseveration, and semantic clustering in individuals with manifest HD have also been detected by the CVLT-I and II (Graves et al, 2017;Kramer et al, 1988;Massman et al, 1990Massman et al, , 1992Massman et al, , 1993.…”

Central Cognitive Processing Speed Is an Early Marker of Huntington's Disease Onset

“…By the time individuals are diagnosed with manifest HD, many will demonstrate measurable cognitive impairment on standardized neuropsychological assessments. [3][4][5][6][7][8] Therefore, it is crucial to examine the nature of neurocognitive changes that occur during the premanifest stages of HD, thereby improving the predictability of disease progression and possibly providing earlier opportunities for cognitive intervention. 9 Several studies have suggested that measures of executive function and processing speed-such as the Symbol Digits Modality Test (SDMT), Trail Making Test Part B, and Stroop-are particularly sensitive to early impairment in HD gene carriers.…”

“…In view of the potentially prolonged nature of the premanifest stage, Ross and colleagues 2 proposed that premanifest HD be composed of the following 2 stages: presymptomatic HD (pre‐HD; furthest from HD diagnosis) and prodromal HD (pro‐HD; closest to HD diagnosis). By the time individuals are diagnosed with manifest HD, many will demonstrate measurable cognitive impairment on standardized neuropsychological assessments 3–8 . Therefore, it is crucial to examine the nature of neurocognitive changes that occur during the premanifest stages of HD, thereby improving the predictability of disease progression and possibly providing earlier opportunities for cognitive intervention 9 …”