Low Cognitive Awareness, but Not Complaint, is a Good Marker of Preclinical Alzheimer’s Disease

Article type: Research Article

Authors: Cacciamani, Federica^a | Tandetnik, Caroline^{a; b} | Gagliardi, Geoffroy^a | Bertin, Hugo^{c; d} | Habert, Marie-Odile^{c; d} | Hampel, Harald^{a; e; f; g} | Boukadida, Laurie^a | Révillon, Marie^a | Epelbaum, Stéphane^{a; e; g; 1; *} | Dubois, Bruno^{a; e; g; 1} | INSIGHT-PreAD study group

Collaborators: Audrain, C | Auffret, A | Bakardjian, H | Baldacci, F | Batrancourt, B | Benakki, I | Benali, H | Bertin, H | Bertrand, A | Boukadida, L | Cacciamani, F | Causse, V | Cavedo, E | Cherif Touil, S | Chiesa, P A | Colliot, O | Dalla Barba, G | Depaulis, M | Dos Santos, A | Dubois, B | Dubois, M | Epelbaum, S | Fontaine, B | Francisque, H | Gagliardi, G | Genin, A | Genthon, R | Glasman, P | Gombert, F | Habert, M O | Hampel, H | Hewa, H | Houot, M | Jungalee, N | Kas, A | Kilani, M | La Corte, V | Le Roy, F | Lehericy, S | Letondor, C | Levy, M | Lista, S | Lowrey, M | Ly, J | Makiese, O | Masetti, I | Mendes, A | Metzinger, C | Michon, A | Mochel, F | Nait Arab, R | Nyasse, F | Perrin, C | Poirier, F | Poisson, C | Potier, M C | Ratovohery, S | Revillon, M | Rojkova, K | Santos-Andrade, K | Schindler, R | Servera, M C | Seux, L | Simon, V | Skovronsky, D | Thiebaut, M | Uspenskaya, O | Vlaincu, M

Affiliations: [a] Département de Neurologie, Institut de laMémoire et de la Maladie d’Alzheimer (IM2A), Hôpital de laPitié-Salpêtrière, AP-HP, Paris, France | [b] Laboratory of Psychopathology and HealthPsychology (EA4057), Paris Descartes University, Sorbonne ParisCité, France | [c] CATI multicenter neuroimagingplatform (cati-neuroimaging.com), Paris, France | [d] Service de Médecine Nucléaire, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France | [e] Institut du Cerveau et de la MoelleÉpinière (ICM), Hôpital de laPitié-Salpêtrière, AP-HP, Paris, France | [f] AXA Research Fund & UPMC Chair, Paris, France | [g] Sorbonne Universities, Université Pierre etMarie Curie-Paris 6, Paris, France

Correspondence: [*] Correspondence to: Dr. Stéphane Epelbaum, Institut de la mémoire et de la maladie d’Alzheimer, Hôpital de la Pitié-Salpêtrière, 47–83 Boulevard de l’Hôpital, 75013 Paris, France. Tel.: +33 142167522; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Subjective cognitive decline (SCD) may result from many conditions, including Alzheimer’s disease (AD). Objective:In this study, we searched for a specific pattern of SCD in asymptomatic individuals at risk for AD. Methods:Cognitively normal older adults (N = 318) reporting SCD and their informants were enrolled in the INSIGHT-PreAD cohort. We examined the relationship between six SCD measures and both cognitive scores and AD neuroimaging markers (amyloid burden, hippocampal atrophy and brain hypometabolism). An awareness of cognitive decline index (ACDI) has been introduced based on the subject-informant discrepancy in a questionnaire of SCD and participants with low versus high awareness were compared. Results:Scores in the INSIGHT-PreAD SCD questionnaires did not correlate with AD neuroimaging markers. As well, no correlation has been found between SCD measures and cognitive scores. Comparing subjects with a low (n = 19) and high (n = 86) level of awareness, no significant difference in terms of demography, neuropsychiatric symptoms, autonomy, quality of life, cognition, and hippocampal volume was found. However, the “low awareness” group showed greater amyloid burden and lower cortical metabolism, compared to the “high awareness” group. Conclusion:This study provided additional evidence that reporting SCD by itself is not a specific symptom of preclinical AD. Conversely, a low cognitive awareness (namely, when subjects report fewer difficulties than their relatives do) may represent a very early form of anosognosia and serve as a specific indicator of preclinical AD. This finding is of key importance as an enrichment factor to consider in both clinical practice and research trials.

Keywords: Alzheimer’s disease, awareness, biomarkers, cognitive complaints, subjective cognitive decline

DOI: 10.3233/JAD-170399

Journal: Journal of Alzheimer's Disease, vol. 59, no. 2, pp. 753-762, 2017