Hippocampal and striatal volumes correlate with spatial memory impairment in Huntington's disease.

Spatial memory impairments are observed in people with Huntington's disease (HD), however, the domain of spatial memory has received little focus when characterizing the cognitive phenotype of HD. Spatial memory is traditionally thought to be a hippocampal-dependent function, while the neuropathology of HD centers on the striatum. Alongside spatial memory deficits in HD, recent neurocognitive theories suggest that a larger brain network is involved, including the striatum. We examined the relationship between hippocampal and striatal volumes and spatial memory in 36 HD gene expansion carriers, including premanifest (n = 24) and early manifest HD (n = 12), and 32 matched healthy controls. We assessed spatial memory with Paired Associates Learning, Rey-Osterrieth Complex Figure Test, and the Virtual House task, which assesses three components of spatial memory: navigation, object location, and plan drawing. Caudate nucleus, putamen, and hippocampal volumes were manually segmented on T1-weighted MR images. As expected, caudate nucleus and putamen volumes were significantly smaller in the HD group compared to controls, with manifest HD having more severe atrophy than the premanifest HD group. Hippocampal volumes did not differ significantly between HD and control groups. Nonetheless, on average, the HD group performed significantly worse than controls across all spatial memory tasks. The spatial memory components of object location and recall of figural and topographical drawings were associated with striatal and hippocampal volumes in the HD cohort. We provide a case to include spatial memory impairments in the cognitive phenotype of HD, and extend the neurocognitive picture of HD beyond its primary pathology within the striatum.

Discrete changes in the frequency and functions of autobiographical reminiscence in Huntington's disease.

Autobiographical memory is widely posited to serve self, social and directive functions. Recent evidence suggests marked autobiographical memory impairments in Huntington's disease (HD), however, no study to date has determined how the perceived functions of autobiographical reminiscence may be altered in HD. The current study aimed to assess the self-reported frequency and function of autobiographical reminiscence in HD. We assessed autobiographical reminiscence in late premanifest (n = 16) and early stage HD (n = 14), relative to healthy controls (n = 30). Participants completed the Thinking About Life Experiences Scale Revised (TALE-R), which measures three putative functions of autobiographical memory (self, social, directive). People with manifest HD reported talking less frequently about the past compared to controls. In contrast, no group differences were found in terms of thinking about the past. Manifest HD participants further reported using their autobiographical memories for social functions less frequently compared to controls. No other group differences were evident in terms of self or directive functions of autobiographical memory. These self-report findings complement recent reports of autobiographical memory disruption on performance-based tasks in HD. Future studies exploring how changes in autobiographical reminiscence impact a sense of self continuity in HD will be important in this regard.

'Real-life' hippocampal-dependent spatial memory impairments in Huntington's disease.

Hippocampal-dependent spatial memory impairments are seen in Huntington's disease animal models. Similar impairments were recently reported in Huntington's disease participants on analogous spatial memory tasks (e.g., virtual Morris Water Maze), however, these tasks do not translate well to the range of functions involved in day-to-day spatial cognition. In this study we examined 'real-life' hippocampal-dependent spatial memory in Huntington's disease participants. We studied premanifest Huntington's disease (N = 24), early manifest Huntington's disease (N = 14), and matched healthy controls (N = 33) with a virtual environment, which demanded spatial memory function on three levels: navigation, object location, and plan drawing. To examine the case for hippocampal-dependent spatial memory more closely, we compared the performance of our Huntington's disease participants to that of a group of temporal lobe epilepsy patients (N = 30) who were previously tested on the virtual environment. Spatial memory performance was also compared to two common neuropsychological tests of spatial cognition, the Paired Associates Learning from the Cambridge Neuropsychological Automated Test Battery, and the Rey-Osterrieth Complex Figure Test. People with early manifest Huntington's disease were impaired across all spatial memory tasks. Premanifest Huntington's disease participants were most notably impaired on the object location measure of the virtual environment, which is heavily dependent on hippocampal function, but showed no such impairments on the Paired Associates Learning or the Rey-Osterrieth Complex Figure Test. Object location memory and navigation performance did not differ between people with Huntington's disease and temporal lobe epilepsy. Aligned with studies in Huntington's disease animal models, 'real-life' spatial memory is impaired in people with Huntington's disease prior to clinical diagnosis. This alignment has important implications for testing treatments for Huntington's disease. From the standpoint of neurodegeneration, the dependence of our spatial memory measures on hippocampal function extends the focus of cognitive assessment research in Huntington's disease beyond its primary pathology within the striato-frontal circuit.

Pervasive autobiographical memory impairments in Huntington's disease.

Autobiographical memory dysfunction is a pervasive feature of neurodegenerative disorders, but less is known about the integrity of autobiographical memory in Huntington's disease (HD). Deficits in anterograde verbal episodic memory on traditional neuropsychological tests have been detected in HD, however, whether personally-relevant autobiographical retrieval is also affected is unknown. We examined autobiographical memory performance in 26 participants genetically confirmed to have HD who were in the peri-manifest stage of the disease (including 12 in the late premanifest stage and 14 who were early diagnosed), and 24 matched controls using the Autobiographical Interview (AI), a semi-structured interview assessing retrieval of autobiographical details from discrete epochs across the lifetime. Relative to controls, people with HD exhibited global episodic autobiographical memory impairments, regardless of recency or remoteness of the memory being retrieved. While specific cues bolstered the retrieval of episodic (internal) details in HD participants, their performance remained significantly below that of controls. Moreover, following probing, people with HD retrieved more extraneous (external) details not directly related to the autobiographical event they originally retrieved, including semantic details, repetitions, and metacognitive statements. Our results reveal marked autobiographical memory dysfunction in HD, not directly attributable to strategic retrieval deficits, and suggest that autobiographical memory impairment may represent an overlooked feature of the cognitive phenotype of HD.

Using warnings to reduce categorical false memories in younger and older adults.

Warnings about memory errors can reduce their incidence, although past work has largely focused on associative memory errors. The current study sought to explore whether warnings could be tailored to specifically reduce false recall of categorical information in both younger and older populations. Before encoding word pairs designed to induce categorical false memories, half of the younger and older participants were warned to avoid committing these types of memory errors. Older adults who received a warning committed fewer categorical memory errors, as well as other types of semantic memory errors, than those who did not receive a warning. In contrast, young adults' memory errors did not differ for the warning versus no-warning groups. Our findings provide evidence for the effectiveness of warnings at reducing categorical memory errors in older adults, perhaps by supporting source monitoring, reduction in reliance on gist traces, or through effective metacognitive strategies.