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

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.

Neuropsychiatric symptoms in at-risk groups for AD dementia and their association with worry and AD biomarkers—results from the DELCODE study

“…Taking into account the results of our analyses, changes of Aß42 might manifest as early symptoms on these neuropsychiatric domains in particular. However, longitudinal analyses are necessary to explore the causality of this relationship, especially considering the concept of NPS as early manifestations of frontotemporal dementia (FTD) [13,[42][43][44].…”

Sex differences in the association of mild behavioral impairment with cognitive aging

“…41 In addition, decreased motivation and psychotic symptoms have been found to be strong predictors of disease progression in frontotemporal degeneration (FTD), which appears to be more common in males. [42][43][44] Moreover, recent findings show that females with behavioral variant of FTD have greater ability to cope with neuropathological changes compared to males and they exhibit less behavioral symptoms, including apathy, despite the same level of atrophy burden. 45 In contrast, progression of AD, in which females account for 60% of patients 2 , has been more often linked to the presence of depressive symptoms.…”

“…45 In contrast, progression of AD, in which females account for 60% of patients 2 , has been more often linked to the presence of depressive symptoms. 44,46 Several limitations need to be mentioned. Participants were not representative of the general population of the United Kingdom, as females, individuals with higher education and White people were overrepresented.…”

Insights into the Pathophysiology of Psychiatric Symptoms in Central Nervous System Disorders: Implications for Early and Differential Diagnosis

“…Psychiatric symptoms can appear during neurodegenerative and neuroinflammatory diseases with a variable prevalence, depending on the specific disease and the considered psychopathological manifestation [ 8 , 21 , 22 ]. Indeed, a wide range of psychopathological expressions including mood, anxiety, psychotic and obsessive-compulsive symptoms (OCS) can be observed [ 23 , 24 ]. Furthermore, subjects affected by CNS diseases could present with more psychiatric symptoms together, thus resulting in a more complex clinical picture [ 5 , 25 ].…”

“…During this phase, psychiatric symptoms may frequently occur. Depressive symptoms are reported in AD prior to mild cognitive impairment (MCI) with a prevalence of about 20% [ 28 , 31 ], as well as in preclinical bvFTD, where a prevalence up to 40% has been described [ 23 , 32 ]. Depression during the preclinical stages of AD and bvFTD can be often associated with other affective symptoms and mood changes [ 15 , 33 ].…”