Brain connectivity and metacognition in persons with subjective cognitive decline (COSCODE): rationale and study design

Federica Ribaldi; Christian Chicherio; Daniele Altomare; Marta Martins; Szymon Tomczyk; Ileana Jelescu; Enrique Maturana; Max Scheffler; Sven Haller; Karl-Olof Lövblad; Michela Pievani; Valentina Garibotto; Matthias Kliegel; Giovanni B Frisoni

doi:10.1186/s13195-021-00846-z

Brain connectivity and metacognition in persons with subjective cognitive decline (COSCODE): rationale and study design

Alzheimers Res Ther. 2021 May 25;13(1):105. doi: 10.1186/s13195-021-00846-z.

Authors

Federica Ribaldi^{1

2}, Christian Chicherio^{3

4}, Daniele Altomare^{5

3}, Marta Martins⁵, Szymon Tomczyk⁵, Ileana Jelescu^{6

7}, Enrique Maturana⁸, Max Scheffler⁹, Sven Haller^{10

11

12

13}, Karl-Olof Lövblad¹⁴, Michela Pievani¹⁵, Valentina Garibotto^{16

17}, Matthias Kliegel^{4

18}, Giovanni B Frisoni^{5

3}

Affiliations

¹ Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland. [email protected].
² Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland. [email protected].
³ Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland.
⁴ Center for Interdisciplinary Study of Gerontology and Vulnerability (CIGEV), University of Geneva, Geneva, Switzerland.
⁵ Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland.
⁶ CIBM Center for Biomedical Imaging, Lausanne, Switzerland.
⁷ Animal Imaging and Technology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
⁸ Department of Radiology, Geneva University Hospitals, Geneva, Switzerland.
⁹ Division of Radiology, Geneva University Hospitals, Geneva, Switzerland.
¹⁰ CIMC - Centre d'Imagerie Médicale de Cornavin, Geneva, Switzerland.
¹¹ Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
¹² Faculty of Medicine of the University of Geneva, Geneva, Switzerland.
¹³ Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, P. R. China.
¹⁴ Neurodiagnostic and Neurointerventional Division, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland.
¹⁵ Laboratory of Alzheimer's Neuroimaging and Epidemiology (LANE), IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
¹⁶ Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTlab), Geneva University Neurocenter and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁷ Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland.
¹⁸ Cognitive Aging Lab, Faculty of Psychology and Educational Sciences, University of Geneva, Geneva, Switzerland.

Abstract

Background: Subjective cognitive decline (SCD) is the subjective perception of a decline in memory and/or other cognitive functions in the absence of objective evidence. Some SCD individuals however may suffer from very early stages of neurodegenerative diseases (such as Alzheimer's disease, AD), minor psychiatric conditions, neurological, and/or somatic comorbidities. Even if a theoretical framework has been established, the etiology of SCD remains far from elucidated. Clinical observations recently lead to the hypothesis that individuals with incipient AD may have overestimated metacognitive judgements of their own cognitive performance, while those with psychiatric disorders typically present underestimated metacognitive judgements. Moreover, brain connectivity changes are known correlates of AD and psychiatric conditions and might be used as biomarkers to discriminate SCD individuals of different etiologies. The aim of the COSCODE study is to identify metacognition, connectivity, behavioral, and biomarker profiles associated with different etiologies of SCD. Here we present its rationale and study design.

Methods: COSCODE is an observational, longitudinal (4 years), prospective clinical cohort study involving 120 SCD, and 80 control study participants (40 individuals with no cognitive impairment, and 40 living with mild cognitive impairment - MCI, or dementia due to AD), all of which will undergo diffusion magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) as well as behavioral and biomarker assessments at baseline and after 1 and 2 years. Both hypothesis-driven and data-driven cluster analysis approaches will be used to identify SCD sub-types based on metacognition, connectivity, behavioral, and biomarker features.

Conclusion: COSCODE will allow defining and interpreting the constellation of signs and symptoms associated with different etiologies of SCD, paving the way to the development of cost-effective risk assessment and prevention protocols.

Keywords: Alzheimer’s disease biomarkers; Connectivity; Metacognition; Subjective cognitive decline.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / diagnostic imaging
Cognitive Dysfunction* / diagnostic imaging
Cohort Studies
Humans
Metacognition*
Neuropsychological Tests
Prospective Studies