First presentation with neuropsychiatric symptoms in autosomal dominant Alzheimer's disease: the Dominantly Inherited Alzheimer's Network Study

• Type of Material: Article
• Authors: Antoinette O'Connor, University College London; Helen Rice, University College London; Josephine Barnes, University College London; Natalie S. Ryan, University College London; Kathy Y. Liu, University College London; Ricardo Francisco Allegri, Neurological Research Institute FLENI; Sarah Berman, University of Pittsburgh; Allan Levey, Emory University
• Language: English
• Date: 2022-12-15
• Publisher: BMJ PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2023.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/jnnp-2022-329843
• Title of Journal or Parent Work: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
• Volume: 94
• Issue: 5
• Start Page: 403
• End Page: 405
• Grant/Funding Information: Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer Network (DIAN, U19AG032438) funded by the National Institute on Ageing (NIA), the Alzheimer’s Association (SG-20–6 90 363-DIAN), the German Centre for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI), Partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, AMED, and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), Spanish Institute of Health Carlos III (ISCIII), Canadian Institutes of Health Research (CIHR), Canadian Consortium of Neurodegeneration and Ageing, Brain Canada Foundation, and Fonds de Recherche du Québec – Santé. This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. We acknowledge the altruism of the participants and their families and contributions of the DIAN research and support staff at each of the participating sites for their contributions to this study. AO'C acknowledges support from an Alzheimer’s Society clinical research training fellowship (AS-CTF18-001) and from the Rosetrees Trust (M668). NSR is supported by a University of London Chadburn Academic Clinical Lectureship. KYL is supported by the UK Medical Research Council (MRC) (MR/S021418/1). This work was supported by the NIHR UCLH/UCL Biomedical Research Centre, the Rosetrees Trust, the MRC Dementia Platform UK and the UK Dementia Research Institute at UCL which receives its funding from UK DRI (UKDRI-1001), funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. NCF has served on advisory boards or as a consultant for Biogen, Ionis, Lilly, and Roche (all payments to UCL) and has served on a data safety monitoring board for Biogen.
• Keywords: BEHAVIOURAL DISORDER; Clinical Neurology; Neurosciences & Neurology; NEUROPSYCHIATRY; Life Sciences & Biomedicine; ALZHEIMER'S DISEASE; Surgery; COGNITION; Science & Technology; Psychiatry
• Research Categories: Health Sciences, Medicine and Surgery; Psychology, Cognitive; Biology, Neuroscience

Abstract

Behavioural changes and neuropsychiatric symptoms (NPS) commonly occur in Alzheimer’s disease (AD) but may not be recognised as AD-related when they are the presenting feature. NPS are important as they are associated with greater functional impairment, poorer quality of life, accelerated cognitive decline and worsened caregiver burden.1 Autosomal dominant AD (ADAD), although <1% of total AD cases, provides a valuable opportunity to study the clinical heterogeneity of AD. The young age at onset reduces the prevalence of age-related comorbid pathologies and the near 100% penetrance of pathogenic mutations reduces the likelihood of misdiagnosis.2 Anxiety and depression commonly occur in ADAD family members, with increased levels of depression having been found among predementia female mutation carriers.3 Subsequent studies, however, have shown that anxiety and/or depression are common regardless of mutation status, occurring in almost one in three at-risk individuals, with one study reporting a higher rate of depression in non-carriers (17%) than asymptomatic carriers (5%).4 5 Despite the high frequency of NPS in ADAD families, relatively little is known about the proportion of ADAD cases who present with predominantly behavioural symptoms. Our aims were to assess the first reported clinical change in symptomatic ADAD, to compare presentations across genotypes, and to compare cognitive performance between behavioural and cognitive-led presentations.