Neuropsychiatric Symptoms as Predictors of Clinical Course in Neurodegeneration. A Longitudinal Study.

José Manuel Santacruz Escudero,José Manuel Santacruz Escudero,José Manuel Santacruz Escudero,Hernando Santamaría-García,Hernando Santamaría-García,Álvaro Palacios,Jonathan Beltrán,Diana Matallana,Pablo Reyes,Pablo Reyes,Claudia Marcela Chimbí,Victor Perez-Sola

doi:10.3389/fnagi.2019.00176

Abstract

Background: To study the extent to which neuropsychiatric symptoms (NPS) influence the cognitive and functional decline in frontotemporal degeneration (FTD) and Alzheimer’s disease (AD).Methods: We assessed the progression of NPS and their influence on cognitive and functional progression in a group of FTD (n = 36) and AD patients (n = 47) at two different stages of the disease (2.5 years). A standardized scale was used to assess NPS—the Columbia University Scale for Psychopathology in Alzheimer’s Disease (CUSPAD)—which tracks different symptoms including depression, psychotic symptoms, as well as sleep and conduct problems. In addition, in a subsample of patients (AD n = 14 and FTD n = 14), we analyzed another group of NPS by using the Neuropsychiatric Inventory (NPI). Cognitive declines were tracked by using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE), while functionality was tracked by using the Lawton scale and the Barthel Index.Results: The presence of NPS impacts cognitive and functional decline in both groups of patients 2.5 years after disease onset. However, we observed a dissociable profile of the affectation of NPS in each group. In the AD group, results indicate that the progression of depressive symptoms and sleep problems predict cognitive and functional decline. In contrast, the progression of a mixed group of NPS, including conduct problems and delusions, predicts cognitive and functional decline in FTD.Conclusion: The presence of NPS has a critical impact on the prediction of cognitive decline in FTD and AD patients after 2.5 years of disease progression. Our results demonstrate the importance of assessing different types of NPS in neurodegenerative disorders which, in turn, predict disease progression. Future studies should assess the role of NPS in predicting different neurocognitive pathways and in neurodegeneration.

Highlights

Frontotemporal degeneration (FTD) and Alzheimer’s disease (AD) are prevalent neurodegenerative diseases which generate alterations in different cognitive and behavioral processes and have a considerable impact on the functionality of patients (Piguet et al, 2011; Livingston et al, 2017).It is usual for patients with FTD to present alterations in the frontal, insular, and temporal brain areas, which are related to alterations in social behavior and executive functions (Piguet et al, 2011; Rascovsky et al, 2011; Sedeño et al, 2016)
Psychotic symptoms presented in AD and FTD are associated with difficulties in episodic and working memory, poor reading of internal feelings, emotional dysregulation and inaccurate conclusions on reality associated with right frontal hypofunction and impaired activity of medial temporal areas (Mendez et al, 2008)
FTD and AD groups differed in age at disease onset (F(1,82) = 13.12, p < 0.001) as AD were older than FTD patients [AD = 68.6 years (SD = 8.2 years) and FTD = 60.7 years (SD = 7.5 years)]

Summary

Introduction

Frontotemporal degeneration (FTD) and Alzheimer’s disease (AD) are prevalent neurodegenerative diseases which generate alterations in different cognitive and behavioral processes and have a considerable impact on the functionality of patients (Piguet et al, 2011; Livingston et al, 2017).It is usual for patients with FTD to present alterations in the frontal, insular, and temporal brain areas, which are related to alterations in social behavior and executive functions (Piguet et al, 2011; Rascovsky et al, 2011; Sedeño et al, 2016). Frontotemporal degeneration (FTD) and Alzheimer’s disease (AD) are prevalent neurodegenerative diseases which generate alterations in different cognitive and behavioral processes and have a considerable impact on the functionality of patients (Piguet et al, 2011; Livingston et al, 2017). Cognitive, language, and praxis alterations in AD have been associated with progressive atrophy in parieto-temporal areas (Dubois et al, 2014) Both AD and FTD tend to exhibit neuropsychiatric symptoms (NPS; Ismail et al, 2016), which are considered relevant indexes for the determination of disease severity and progression (Teng et al, 2007; Peters et al, 2015). To study the extent to which neuropsychiatric symptoms (NPS) influence the cognitive and functional decline in frontotemporal degeneration (FTD) and Alzheimer’s disease (AD)

Methods

Results

Discussion

Conclusion