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

• 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
• Journal Title: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
• Volume: Volume 94, Number 5
• Publisher: BMJ PUBLISHING GROUP | 2022-12-15, Pages 403-405
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1136/jnnp-2022-329843
• Subjects: Biology, Neuroscience; Health Sciences, Medicine and Surgery; Psychology, Cognitive
• Keywords: Science & Technology; Life Sciences & Biomedicine; Clinical Neurology; Psychiatry; Surgery; Neurosciences & Neurology; ALZHEIMER'S DISEASE; BEHAVIOURAL DISORDER; COGNITION; NEUROPSYCHIATRY

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.