Luciana M Fonseca1,2,3, Concepcion Padilla2, Elizabeth Jones2, Natalie Neale4, Glenda G Haddad1, Guilherme P Mattar1, Eriton Barros5, Isabel C H Clare2,6,7, Geraldo F Busatto1,8, Cassio M C Bottino1, Marcelo Q Hoexter9, Anthony J Holland2, Shahid Zaman2,6. 1. Programa Terceira Idade (PROTER, Old Age Research Group), Department and Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil. 2. Department of Psychiatry, University of Cambridge, Cambridge, UK. 3. Department of Medical Education and Clinical Science, Washington State University, Spokane, Washington, USA. 4. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 5. Institute of Mathematics and Statistics, University of São Paulo, São Paulo, Brazil. 6. Cambridgeshire & Peterborough NHS Foundation Trust, Cambridge, UK. 7. NIHR Applied Research Collaboration East of England, Cambridge, UK. 8. Laboratorio de Neuroimagem em Psiquiatria (LIM21, Laboratory of Psychiatric Neuroimaging), Department and Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil. 9. Projeto Transtornos do Espectro Obsessivo-Compulsivo (PROTOC, Obsessive-Compulsive Spectrum Disorders Program), Department and Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil.
Abstract
The presence of age-related neuropathology characteristic of Alzheimer's disease (AD) in people with Down syndrome (DS) is well-established. However, the early symptoms of dementia may be atypical and appear related to dysfunction of prefrontal circuitry. OBJECTIVE: To characterize the initial informant reported age-related neuropsychiatric symptoms of dementia in people with DS, and their relationship to AD and frontal lobe function. METHODS: Non-amnestic informant reported symptoms (disinhibition, apathy, and executive dysfunction) and amnestic symptoms from the CAMDEX-DS informant interview were analyzed in a cross-sectional cohort of 162 participants with DS over 30 years of age, divided into three groups: stable cognition, prodromal dementia, and AD. To investigate age-related symptoms prior to evidence of prodromal dementia we stratified the stable cognition group by age. RESULTS: Amnestic and non-amnestic symptoms were present before evidence of informant-reported cognitive decline. In those who received the diagnosis of AD, symptoms tended to be more marked. Memory impairments were more marked in the prodromal dementia than the stable cognition group (OR = 35.07; P < .001), as was executive dysfunction (OR = 7.16; P < .001). Disinhibition was greater in the AD than in the prodromal dementia group (OR = 3.54; P = .04). Apathy was more pronounced in the AD than in the stable cognition group (OR = 34.18; P < .001). CONCLUSION: Premorbid amnestic and non-amnestic symptoms as reported by informants increase with the progression to AD. For the formal diagnosis of AD in DS this progression of symptoms needs to be taken into account. An understanding of the unique clinical presentation of DS in AD should inform treatment options.
The presence of age-related neuropathology characteristic of Alzheimer's disease (AD) in people with Down syndrome (DS) is well-established. However, the early symptoms of dementia may be atypical and appear related to dysfunction of prefrontal circuitry. OBJECTIVE: To characterize the initial informant reported age-related neuropsychiatric symptoms of dementia in people with DS, and their relationship to AD and frontal lobe function. METHODS: Non-amnestic informant reported symptoms (disinhibition, apathy, and executive dysfunction) and amnestic symptoms from the CAMDEX-DS informant interview were analyzed in a cross-sectional cohort of 162 participants with DS over 30 years of age, divided into three groups: stable cognition, prodromal dementia, and AD. To investigate age-related symptoms prior to evidence of prodromal dementia we stratified the stable cognition group by age. RESULTS: Amnestic and non-amnestic symptoms were present before evidence of informant-reported cognitive decline. In those who received the diagnosis of AD, symptoms tended to be more marked. Memory impairments were more marked in the prodromal dementia than the stable cognition group (OR = 35.07; P < .001), as was executive dysfunction (OR = 7.16; P < .001). Disinhibition was greater in the AD than in the prodromal dementia group (OR = 3.54; P = .04). Apathy was more pronounced in the AD than in the stable cognition group (OR = 34.18; P < .001). CONCLUSION: Premorbid amnestic and non-amnestic symptoms as reported by informants increase with the progression to AD. For the formal diagnosis of AD in DS this progression of symptoms needs to be taken into account. An understanding of the unique clinical presentation of DS in AD should inform treatment options.
Authors: Kari Knox; Justin Stanley; James A Hendrix; Hampus Hillerstrom; Taylor Dunn; Jillian Achenbach; Brian A Chicoine; Florence Lai; Ira Lott; Sanja Stanojevic; Susan E Howlett; Kenneth Rockwood Journal: J Patient Rep Outcomes Date: 2021-01-11
Authors: Emili Rodríguez-Hidalgo; Javier García-Alba; Maria Buxó; Ramon Novell; Susana Esteba-Castillo Journal: Int J Environ Res Public Health Date: 2022-08-30 Impact factor: 4.614