Saul Martinez-Horta1, Jesus Perez-Perez2, Erik van Duijn3, Ramon Fernandez-Bobadilla1, Mar Carceller4, Javier Pagonabarraga2, Berta Pascual-Sedano2, Antonia Campolongo2, Jesus Ruiz-Idiago5, Frederic Sampedro6, G Bernhard Landwehrmeyer7, Jaime Kulisevsky8. 1. Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain; Universitat Oberta de Catalunya (UOC), Barcelona, Spain. 2. Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain. 3. Department of Psychiatry, Leiden University Medical Centre, Leiden, and Centre for Mental Health Care Delfland, Delft, The Netherlands. 4. Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. 5. Hospital Mare de Déu de la Mercé, Barcelona, Spain. 6. Faculty of Medicine, Autonomous University of Barcelona, Spain. 7. Department of Neurology, University of Ulm, Ulm, Germany. 8. Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain; Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain; Universitat Oberta de Catalunya (UOC), Barcelona, Spain. Electronic address: jkulisevsky@santpau.cat.
Abstract
BACKGROUND: Neuropsychiatric symptoms are common features of Huntington's disease (HD). Whereas most studies have focused on cognitive and neuroimaging markers of disease progression, little is known about the prevalence of neuropsychiatric symptoms in premanifest mutation carriers far-from and close-to disease onset. METHODS: We obtained neurological, cognitive and behavioral data from 230 participants classified as premanifest far-from (preHD-A) and close-to (preHD-B) motor-based disease onset, early-symptomatic (early-HD), and healthy controls. Frequency and severity of neuropsychiatric symptoms were assessed with the short Problem Behaviors Assessment for HD (PBA-s). The odds-ratio (OR) to present symptoms in the clinical range was calculated using the control group as reference. Logistic regression analysis was used to explore relationships between neuropsychiatric symptoms and medication use. RESULTS: Prevalence of depression was similar in all groups. Apathy was already present in 32% of preHD-A increasing to 62% of early-HD patients. The probability of presenting apathetic symptoms was 15-88 times higher in preHD-A and preHD-B respectively than in healthy controls. Irritability and executive dysfunction were present in both preHD-B and early-HD. CONCLUSION: Neuropsychiatric symptoms are highly prevalent in HD, already in the premanifest stage, with increasing prevalence of irritability, apathy and executive dysfunction closer to onset. Compared to controls, HD mutation carriers have the highest probability to develop apathy, with an increasing prevalence along disease stages. Our findings confirm the high prevalence of neuropsychiatric symptoms in HD, already many years before the onset of motor symptoms, with apathy as an early manifestation and core neuropsychiatric feature of the disease.
BACKGROUND:Neuropsychiatric symptoms are common features of Huntington's disease (HD). Whereas most studies have focused on cognitive and neuroimaging markers of disease progression, little is known about the prevalence of neuropsychiatric symptoms in premanifest mutation carriers far-from and close-to disease onset. METHODS: We obtained neurological, cognitive and behavioral data from 230 participants classified as premanifest far-from (preHD-A) and close-to (preHD-B) motor-based disease onset, early-symptomatic (early-HD), and healthy controls. Frequency and severity of neuropsychiatric symptoms were assessed with the short Problem Behaviors Assessment for HD (PBA-s). The odds-ratio (OR) to present symptoms in the clinical range was calculated using the control group as reference. Logistic regression analysis was used to explore relationships between neuropsychiatric symptoms and medication use. RESULTS: Prevalence of depression was similar in all groups. Apathy was already present in 32% of preHD-A increasing to 62% of early-HDpatients. The probability of presenting apathetic symptoms was 15-88 times higher in preHD-A and preHD-B respectively than in healthy controls. Irritability and executive dysfunction were present in both preHD-B and early-HD. CONCLUSION:Neuropsychiatric symptoms are highly prevalent in HD, already in the premanifest stage, with increasing prevalence of irritability, apathy and executive dysfunction closer to onset. Compared to controls, HD mutation carriers have the highest probability to develop apathy, with an increasing prevalence along disease stages. Our findings confirm the high prevalence of neuropsychiatric symptoms in HD, already many years before the onset of motor symptoms, with apathy as an early manifestation and core neuropsychiatric feature of the disease.
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