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

Abstract

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.

Striatal insights: a cellular and molecular perspective on repetitive behaviors in pathology

“…Loss of striatal gray and white matter ( Tabrizi et al, 2011 ; McColgan et al, 2015 ) have been described, along with connectivity alterations. PreHD patients display reduced striatal volume ( Glikmann-Johnston et al, 2021 ), reduction in functional connectivity between the striatum and the motor cortex, and increased connectivity between the striatum and the PFC. Indeed, alterations of the dorsolateral PFC are associated with excessive doubt and repetitive actions in OCD ( Mataix-Cols et al, 2003 ; Abramowitz et al, 2009 ).…”

Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington’s Disease: Mechanisms and Potential Therapeutics

“…For example, volumetric magnetic resonance imaging reports involving HD populations and rodent models consistently detect the loss of gray matter in the hippocampus and other limbic structures [ 29 , 30 , 31 ]. These atrophic changes are frequently correlated with poorer performance on spatial memory tasks in HD individuals and on hippocampal-dependent behavioral assays in rodent models [ 32 , 33 , 34 ]. The psychiatric burden in the HD population is substantially higher than for most neurodegenerative disease patient populations, with some observational reports and meta-analyses suggesting lifetime prevalence of psychiatric disorders to exist between 33 and 76% [ 35 , 36 , 37 ].…”

Cognitive Reserve in Early Manifest Huntington Disease Patients: Leisure Time Is Associated with Lower Cognitive and Functional Impairment

“…Usually, the genetic test is associated with specific psychological and genetic counselling [2]. Neurological features include movement disorders, among which chorea is the landmark, and progressive cognitive decline starting with early emotion recognition deficit [3], spatial memory problems [4], impaired attention functions [5], and finally overt dementia in the later stage of the disease.…”

“…The former hypothesizes that each individual disposes of a certain amount of brain capacity (determined by brain volume, number of neurons, etc.) to withstand the development of neurologic diseases [4]. In contrast, the latter speculates that the nervous system might actively cope with brain damage by using more efficient pre-existing neural networks or recruiting additional brain regions [6][7][8].…”