Cognitive and functional decline in Huntington's disease: Dementia criteria revisited

Abstract

The importance of designating criteria for diagnosing dementia lies in its implications for clinical treatment, research, caregiving, and decision-making. Dementia diagnosis in Huntington's disease (HD) is often based on criteria developed for Alzheimer's disease requiring memory loss. However, it is likely that other cognitive deficits contribute to functional impairment in HD before memory declines. The goal is to identify cognitive deficits that contribute to functional impairment to support dementia criteria that reflect HD neuropathology. Eighty-four HD mutation-positive subjects completed neuropsychological tests and the Unified Huntington's Disease Rating Scale Functional Independence Scale (FIS). Functional impairment was defined as 80 or below on the FIS. Speed of processing, initiation, and attention measures accounted for 70.0% of the variance in FIS ratings (linear regression) and correctly classified 91.7% of subjects as functionally impaired or intact (logistic regression). Measures of memory, motor impairment except dysarthria, neuroleptic use, and depressed mood did not improve prediction. A definition of HD dementia that includes cognitive impairment in at least two areas of cognition but does not require a memory deficit, in the context of impaired functional abilities and a deteriorating course, more accurately reflects HD neuropathology and could lead to improved research methods and patient care.

Dysfunction of the Ubiquitin Ligase Ube3a May Be Associated with Synaptic Pathophysiology in a Mouse Model of Huntington Disease

“…Interestingly, many of the altered signaling pathways are linked with the disruption of synaptic function (11,12). In fact, several studies demonstrate cognitive disturbances in HD patients long before onset of classic motor symptoms like chorea (13)(14)(15). Similarly, transgenic mouse models of HD also show that the onset of symptoms is associated with synaptic and neuronal dysfunction and that neurodegeneration takes place at a much later stage (16 -19).…”

HDQLIFE: development and assessment of health-related quality of life in Huntington disease (HD)

“…Therefore, a measure of motor functioning developed for PD may not be meaningful for HD. Similarly, although cognitive dysfunction in HD overlaps with cognitive dysfunction in Alzheimer disease (AD), individuals with HD typically have ‘‘subcortical’’ deficits (in attention, processing speed, and executive dysfunction), whereas individuals with AD also have prominent ‘‘cortical’’ deficits (in memory, language, and executive dys-function) [12]. Furthermore, generic measures of HRQOL cannot detect subtle differences in function for prodromal HD symptoms [13], and single-item ratings [14, 15] have inadequate sensitivity and reliability to detect change over time [15].…”

Drug or disease - Differentiating and managing motor symptoms associated with late onset Huntington’s disease from extrapyramidal side-effects of antipsychotics

“…Patients generally present with impaired cognition, attention deficits, impaired problem solving, visuospatial problems and constructional abilities [18]. However as the disease progresses, patients have been noted to have cortical features as well such as prominent memory impairment, language difficulties and impairment in executive functions [19]. The patient's marked cognitive problems were most likely indicative of the severity of his Huntington's disease.…”