First Symptoms and Neurocognitive Correlates of Behavioral Variant Frontotemporal Dementia

Article type: Research Article

Authors: Santamaría-García, Hernando^{a; b; c; k} | Reyes, Pablo^{a; k} | García, Adolfo^{b; c; m} | Baéz, Sandra^{b; c} | Martinez, Angela^{a; l} | Santacruz, José Manuel^{a; k; n} | Slachevsky, Andrea^{e; f; g; o; p} | Sigman, Mariano^h | Matallana, Diana^{a; k; q} | Ibañez, Agustín^{b; c; d; i; j; *}

Affiliations: [a] Pontificia Universidad Javeriana Bogotá, Colombia | [b] Laboratory of Experimental Psychology and Neuroscience (LPEN), Institute of Translational and Cognitive Neuroscience (INCyT), INECO Foundation, Favaloro University, Buenos Aires, Argentina | [c] National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina | [d] Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibanez, Santiago, Chile | [e] Gerosciences Center for Brain Health and Metabolism, Avenida Salvador 486, Providencia, Santiago, Chile | [f] Physiopathology Department, ICBM y East Neuroscience Department, Faculty of Medicine, Universidad de Chile, Avenida Salvador 486, Providencia, Santiago, Chile | [g] Cognitive Neurology and Dementia Unit, Neurology Department, Hospital del Salvador, Av. Salvador 364, Providencia, Santiago, Chile | [h] Universidad Torcuato di Tella Laboratorio de Neurociencias, Buenos Aires, Argentina | [i] Universidad Autónoma del Caribe, Barranquilla, Colombia | [j] Centre of Excellence in Cognition and its Disorders, Australian Research Council (ACR), NSW, Australia | [k] Intellectus, Memory and cognition center. Hospital San Ignacio Bogotá, Colombia | [l] Université Lumière Lyon 2 – Laboratoire Dynamique du langage, Lyon, France | [m] Universidad Nacional de Cuyo (UNCuyo), Facultad de Educación Elemental y Especial (FEEyE), Mendoza, Argentina | [n] Departament de Psiquiatria i medicina legal. Universitat Autónoma de Barcelona, Cerdanyola del Vallés, España | [o] Center for Advanced Research in Education (CIAE), Universidad de Chile, 8330014, Santiago, Chile | [p] Neurology Department, Clínica Alemana, Santiago, Chile | [q] Instituto de envejecimiento. Pontificia Universidad Javeriana, Colombia

Correspondence: [*] Correspondence to: Agustín Ibañez, Director of Instituto de Neurociencia Cognitiva y Traslacional (INCyT), Laboratory of Experimental Psychology and Neuroscience Psicología Experimental y Neurociencias (LPEN), Fundación INECO, Universidad Favaloro, José Andrés Pacheco de Melo 1860, C1126AAB CABA, Argentina. Tel./Fax: +54 (11) 4812 0010; E-mail: aibanez@ineco.org.ar.

Abstract: Background: Previous works highlight the neurocognitive differences between apathetic and disinhibited clinical presentations of the behavioral variant frontotemporal dementia (bvFTD). However, little is known regarding how the early presentation (i.e., first symptom) is associated to the neurocognitive correlates of the disease’s clinical presentation at future stages of disease. Objectives: We analyzed the neurocognitive correlates of patients with bvFTD who debuted with apathy or disinhibition as first symptom of disease. Methods: We evaluated the neuropsychological, clinical, and neuroanatomical (3T structural images) correlates in a group of healthy controls (n = 30) and two groups of bvFTD patients (presented with apathy [AbvFTD, n = 18] or disinhibition [DbvFTD, n = 16]). To differentiate groups according to first symptoms, we used multivariate analyses. Results: The first symptom in patients described the evolution of the disease. AbvFTD and DbvFTD patients showed increased brain atrophy and increased levels of disinhibition and apathy, respectively. Whole brain analyzes in AbvFTD revealed atrophy in the frontal, insular, and temporal areas. DbvFTD, in turn, presented atrophy in the prefrontal regions, temporoparietal junction, insula, and temporoparietal region. Increased atrophy in DbvFTD patients (compared to AbvFTD) was observed in frontotemporal regions. Multivariate analyses confirmed that a set of brain areas including right orbitofrontal, right dorsolateral prefrontal, and left caudate were enough to distinguish the patients’ subgroups.∥Conclusion: First symptom in bvFTD patients described the neurocognitive impairments after around three years of disease, playing an important role in the early detection, disease tracking, and neuroanatomical specification of bvFTD, as well as in future research on potential disease-modifying treatments.

Keywords: Apathy, behavioral variant frontotemporal dementia, apathy, first symptom, voxel-based morphometry

DOI: 10.3233/JAD-160501

Journal: Journal of Alzheimer's Disease, vol. 54, no. 3, pp. 957-970, 2016