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Mild behavioral impairment in prodromal Alzheimer´s disease and its association with APOE and BDNF risk genetic polymorphisms

Published online by Cambridge University Press:  02 February 2024

Veronika Matuskova
Affiliation:
Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic
Katerina Veverova
Affiliation:
Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic
Dylan Jester
Affiliation:
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA, USA
Vaclav Matoska
Affiliation:
Department of Clinical Biochemistry, Hematology and Immunology, Homolka Hospital, Prague, Czech Republic.
Zahinoor Ismail
Affiliation:
Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
Katerina Sheardova
Affiliation:
First Department of Neurology, St. Anne’s University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
Hana Horakova
Affiliation:
Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic
Jan Laczó
Affiliation:
Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic
Jakub Hort
Affiliation:
Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic
Martin Vyhnalek*
Affiliation:
Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic
*
Corresponding author: Martin Vyhnalek, Department of Neurology, Charles University, Second Faculty of Medicine, and Motol University Hospital, V Uvalu 84, 150 06 Prague, Czech Republic. Tel.: +420 224 436 800; E-mail: martin.vyhnalek@fnmotol.cz.

Abstract

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Objective:

We aimed to examine the profile and severity of mild behavioral impairment (MBI) in a sample of β-amyloid positive individuals with amnestic mild cognitive impairment (aMCI)compared to cognitively normal older adults (CN). Within aMCI, we further examined the potential influence of APOE and BDN Frisk genetic polymorphisms on MBI severity.

Methods:

We included 64 β-amyloid positive aMCI participants and 50 CN older adults from the Czech Brain Aging Study. The participants underwent neurological, comprehensive neuropsychological examination, APOE and BDNF genotyping, and magnetic resonance imaging.MBI was diagnosed with the Mild behavioral impairment checklist (MBI-C) developed for MBI case detection, and the diagnosis was based on the MBI-C total score ≥7. Additionally, self-report instruments for anxiety (the Beck Anxiety Inventory) and depressive symptoms (the Geriatric Depression Scale-15) were administered. The participants were stratified based on the presence of at least one risk allele in genes for APOE (i.e., e4 carriers and non-carriers) and BDNF (i.e., Met carriers and non-carriers). We used linear regressions to examine the between-group differences.

Results:

MBI symptoms (MBI-C total score ≥1) were present in 28% CN and 83% aMCI. Almost half (48.4%) of the aMCI individuals met the criteria for the MBI syndrome. Compared to the CN, the aMCI group displayed more affective, apathy, and impulse dyscontrol symptoms (p<0.001) but not social inappropriateness or psychotic symptoms. Furthermore, aMCI participants reported more depressive (p<0.01) but similar anxiety symptoms to CN on self-report measures. Within the aMCI group, APOE e4 and BDNF Met carriers did not differ from non-carriers in the severity of NPS in either instrument. However, the results suggested that an interaction between these polymorphisms influenced self-reported anxiety (p=0.034), with Met carriers/e4 non-carriers reporting the highest anxiety levels.

Conclusion:

MBI is frequent in prodromal Alzheimer´s disease and characterized by affective, apathy, and impulse dyscontrol symptoms. APOE and BDNF risk genetic polymorphisms did not influence the NPS severity when considered separately; however, their interaction might influence anxiety, which warrants further investigation.

The research has received funding from the EEA/ Norway Grants 2014-2021 and the Technology Agency of the Czech Republic – project number TO01000215, Ministry of Health of the Czech Republic, grant no. 19-04-00560, National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107) - funded by the European Union – Next Generation EU and GAČR 22-33968S.

Type
Symposia
Copyright
© International Psychogeriatric Association 2024