So Close Yet So Far: Executive Contribution to Memory Processing in Behavioral Variant Frontotemporal Dementia

Article type: Research Article

Authors: Bertoux, Maxime^{a; b; j; *; 1} | Ramanan, Siddharth^{c; 1} | Slachevsky, Andrea^{d; e} | Wong, Stephanie^f | Henriquez, Fernando^g | Musa, Gada^g | Delgado, Carolina^g | Flanagan, Emma^a | Bottlaender, Michel^h | Sarazin, Marieⁱ | Hornberger, Michael^a | Dubois, Bruno^{b; j}

Affiliations: [a] Norwich Medical School, University of East Anglia, UK | [b] Centre de Référence Démence Rares, Pitié-Salpêtrière, Paris, France | [c] Department of Neurology, Manipal Hospital, Bangalore, India | [d] Department of Physiopathology and Neuroscience, Faculty of Medicine, University of Chile, Santiago, Chile | [e] Gerosciences Center for Brain Health and Metabolism, Santiago, Chile | [f] Neurosciences Research Australia, Randwick, Australia | [g] Cognitive Neurology and Dementia, Neurology Department, Hospital del Salvador, Santiago, Chile | [h] NeuroSpin, Commissariat à l’Energie Atomique, Saclay, France | [i] Centre Psychiatrie & Neurosciences, Sainte-Anne, Paris, France | [j] Sorbonne Universités, Paris VI, France

Correspondence: [*] Correspondence to: Dr. Maxime Bertoux, Bob Champion Research and Education Building, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK. Tel.: +44 (0)1603 593061; Fax: +44 (0)1603 593062; E-mail: maxime.bertoux@cantab.net.

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

Abstract: Background: Memory impairment in behavioral variant frontotemporal dementia (bvFTD) is traditionally considered to be mild and attributed to prefrontal cortex dysfunction. Recent studies, however, indicated that some patients can present with a memory impairment of the hippocampal type, showing storage and consolidation deficits in addition to the more executive/prefrontal related encoding and strategic difficulties. Objective: This study aimed to study the relationship between executive functions (EF) and memory processes in bvFTD via a data-driven approach. Method: Participants consisted of 71 bvFTD (among which 60.6% had a lumbar puncture showing non-Alzheimer biomarker profile) and 60 controls (among which 45% had amyloid imaging showing a normal profile). EF were assessed by the Frontal Assessment Battery, semantic/lexical verbal fluency tests, and forward/backward digit spans. Patients were split into amnestic (n = 33) and non-amnestic (n = 38) subgroups based on normative data (total recall score) from the Free and Cued Selective Reminding Test (FCSRT). Relationships between FCSRT subscores and EF measures were explored through hierarchical clustering analysis, partial correlation analysis with an EF component, and automated linear modeling. Results: Convergent findings across the statistical approaches show that, overall, memory performance was independent from EF in bvFTD whereas the relationship was stronger in controls. Indeed, in bvFTD, memory performance did not cluster with EF, was not correlated with the EF component, and was only partially (4% – 12.7%) predicted by EF. Discussion: These findings show that executive dysfunctions cannot solely explain the memory deficits occurring in bvFTD. Indeed, some patients present with a genuine amnesia affecting storage and consolidation abilities, which are independent from executive dysfunctions. On the clinical level, this study highlights the importance of revising the neuropsychological diagnosis criteria for bvFTD.

Keywords: Consolidation, encoding, episodic amnesia, executive functions, Free and Cued Selective Reminding Test, frontotemporal dementia, memory, retrieval, storage

DOI: 10.3233/JAD-160522

Journal: Journal of Alzheimer's Disease, vol. 54, no. 3, pp. 1005-1014, 2016