Measuring Executive Dysfunction Longitudinally and in Relation to Genetic Burden, Brain Volumetrics, and Depression in Prodromal Huntington Disease

• Published in: Archives of clinical neuropsychology Vol. 28; no. 2; pp. 156 - 168
• Main Authors: PAPP, Kathryn V, SNYDER, Peter J, MILLS, James A, DUFF, Kevin, WESTERVELT, Holly J, LONG, Jeffrey D, LOURENS, Spencer, PAULSEN, Jane S
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2013
• Subjects: Adult; Adult and adolescent clinical studies; Biological and medical sciences; Brain - pathology; Corpus Striatum - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Depression; Depression - genetics; Depression - pathology; Depression - psychology; Depressive Disorder - genetics; Depressive Disorder - pathology; Depressive Disorder - psychology; Disease Progression; Executive Function; Female; Follow-Up Studies; Humans; Huntington Disease - genetics; Huntington Disease - pathology; Huntington Disease - psychology; Longitudinal Studies; Male; Medical sciences; Memory, Short-Term; Middle Aged; Mood disorders; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neuropsychological Tests; Organic mental disorders. Neuropsychology; Original Empirical; Problem Solving; Prodromal Symptoms; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Severity of Illness Index; Trinucleotide Repeat Expansion; Neuroimaging; Volumetric analysis; Executive function; Cognitive disorder; Central nervous system; Practice; Prodrome; Cognition; Practice effects/reliable change; Encephalon; Genetics; Norms/normative studies; Degenerative disease; Mood disorder; Human; Nervous system diseases; Genetic disorders; Huntington disease; Depression; Executive functions; Neuroimaging (structural); Huntington's disease; Cerebral disorder; Genetic disease; longitudinal change; Follow up study; Central nervous system disease; Extrapyramidal syndrome
• ISSN: 0887-6177; 1873-5843
• DOI: 10.1093/arclin/acs105

Executive dysfunction (ED) is a characteristic of Huntington disease (HD), but its severity and progression is less understood in the prodromal phase, e.g., before gross motor abnormalities. We examined planning and problem-solving abilities using the Towers Task in HD mutation-positive individuals without motor symptoms (n = 781) and controls (n = 212). Participants with greater disease progression (determined using mutation size and current age) performed more slowly and with less accuracy on the Towers Task. Performance accuracy was negatively related to striatal volume while both accuracy and working memory were negatively related to frontal white matter volume. Disease progression at baseline was not associated with longitudinal performance over 4 years. Whereas the baseline findings indicate that ED becomes more prevalent with greater disease progression in prodromal HD and can be quantified using the Towers task, the absence of notable longitudinal findings indicates that the Towers Task exhibits limited sensitivity to cognitive decline in this population.