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. 2023 Jan 10;24(2):1371.
doi: 10.3390/ijms24021371.

The Synergic Effect of AT(N) Profiles and Depression on the Risk of Conversion to Dementia in Patients with Mild Cognitive Impairment

Marta Marquié  1   2 , Fernando García-Gutiérrez  1 , Adelina Orellana  1   2 , Laura Montrreal  1 , Itziar de Rojas  1   2 , Pablo García-González  1 , Raquel Puerta  1 , Clàudia Olivé  1 , Amanda Cano  1   2 , Isabel Hernández  1 , Maitée Rosende-Roca  1 , Liliana Vargas  1 , Juan Pablo Tartari  1 , Ester Esteban-De Antonio  1 , Urszula Bojaryn  1 , Mario Ricciardi  1 , Diana M Ariton  1 , Vanesa Pytel  1 , Montserrat Alegret  1   2 , Gemma Ortega  1   2 , Ana Espinosa  1   2 , Alba Pérez-Cordón  1 , Ángela Sanabria  1   2 , Nathalia Muñoz  1 , Núria Lleonart  1 , Núria Aguilera  1 , Ainhoa García-Sánchez  1 , Emilio Alarcón-Martín  1 , Lluís Tárraga  1   2 , Agustín Ruiz  1   2 , Mercè Boada  1   2 , Sergi Valero  1   2
Affiliations

The Synergic Effect of AT(N) Profiles and Depression on the Risk of Conversion to Dementia in Patients with Mild Cognitive Impairment

Marta Marquié et al. Int J Mol Sci. .

Abstract

Few studies have addressed the impact of the association between Alzheimer's disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of these two risk factors. AT(N) profiles were created using AD-core biomarkers quantified in cerebrospinal fluid (CSF) (normal, brain amyloidosis, suspected non-Alzheimer pathology (SNAP) and prodromal AD). NPSs were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). A total of 500 individuals with MCI were followed-up yearly in a memory unit. Cox regression analysis was used to determine risk of conversion, considering additive and multiplicative interactions between AT(N) profile and NPSs on the conversion to dementia. A total of 224 participants (44.8%) converted to dementia during the 2-year follow-up study. Pathologic AT(N) groups (brain amyloidosis, prodromal AD and SNAP) and the presence of depression and apathy were associated with a higher risk of conversion to dementia. The additive combination of the AT(N) profile with depression exacerbates the risk of conversion to dementia. A synergic effect of prodromal AD profile with depressive symptoms is evidenced, identifying the most exposed individuals to conversion among MCI patients.

Keywords: CSF; NPSs; dementia; interaction; mild cognitive impairment (MCI); synergic.

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Conflict of interest statement

M.B. has consulted for Araclon, Avid, Grifols, Lilly, Nutricia, Roche, Eisai and Servier. She received fees from lectures and funds for research from Araclon, Biogen, Grifols, Nutricia, Roche and Servier. She reports grants/research funding from Abbvie, Araclon, Biogen Research Limited, Bioiberica, Grifols, Lilly, S.A., Merck Sharp & Dohme, Kyowa Hakko Kirin, Laboratorios Servier, Nutricia S.R.L., Oryzon Genomics, Piramal Imaging Limited, Roche Pharma S.A. and Schwabe Farma Iberica S.L.U., all outside the submitted work. She has not received personal compensations from these organizations. A.R. is member of the scientific advisory board of Landsteiner Genmed and Grifols S.A. A.R. has stocks of Landsteiner Genmed. The rest of the authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Survival curves of conversion to dementia for each AT(N) profile. Note: survival curves of conversion to dementia for each AT(N) profile obtained in the model presented in Table 5. AD: Alzheimer’s Disease; SNAP: Suspected Non-Alzheimer’s Pathology.
Figure 2
Figure 2
Estimated marginal means of cumulative hazard function when combining effects of AT(N) profiles and depression on conversion to dementia. Note: cumulative hazard function adjusted by age, sex, years of formal education, amnestic profile (yes/no), probable MCI (yes/no) APOE ε4 carrier (yes/no) and MMSE at baseline a MMSE: Mini-Mental State Examination; SNAP: Suspected Non-Alzheimer’s Pathology.
See this image and copyright information in PMC

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