Serum levels of soluble TNF-α receptors but not BDNF are associated with apathy symptoms in mild Alzheimer's disease and amnestic mild cognitive impairment

Abstract

Apathy is intimately associated with dementia. Unfortunately, its pathophysiology remains poorly understood. The motivational impairment that characterizes this disorder might share the same inflammatory mechanisms, as suggested by the sickness behavior theory.OBJECTIVEThe primary aim of this study was to investigate the association between apathy symptoms and serum levels of tumor necrosis factor alpha (TNF-α) and its soluble receptors. Brain-derived neurotrophic factor (BDNF) levels were also analyzed since these have been associated with depression, a condition which shares abulic features with apathy.METHODSThe sample consisted of 27 subjects with mild Alzheimer's disease or amnestic mild cognitive impairment, who were submitted to specific apathy evaluation using the Apathy Scale (AS) and provided blood samples for biomarker analysis. Participants were categorized into two groups according to median AS scores (17 points).RESULTSSubjects with higher apathy symptoms (n=13) displayed higher levels of TNF-α soluble receptors (type 1: p=0.03; type 2: p=0.04). No other difference was found between groups.CONCLUSIONThese findings point to the involvement of inflammatory mediators in the genesis of apathy symptoms, as suggested by the sickness behavior theory.

Low-grade inflammation differentiates between symptoms of apathy and depression in community-dwelling older individuals

“…The results of this study are in line with previous findings of an association between CRP level and apathy in elderly women with cognitive impairment (Hall et al, 2012). Similarly, an association between apathy and level of tumor necrosis factor alpha (TNF-α) or its soluble receptors, as markers of inflammation, has been reported in two studies in elderly individuals with cognitive impairment (Hall et al, 2011;Guimarães et al, 2013). In a population-based cohort study of older individuals, CRP was specifically associated with worse performance on information processing speed and attention and executive functioning (Heringa et al, 2014), which are frequent neuropsychological correlates of apathy (Brodaty et al, 2005;Van Reekum et al, 2005).…”

Cerebrolysin in the therapy of mild cognitive impairment and dementia due to Alzheimer's disease: 30 years of clinical use

“…TNF reductions were maximal with the 60 ml dose and were associated to parallel dose‐related improvements in neuropsychiatric symptoms and increases in circulating IGF‐1. These results and the associations of elevated circulating TNF‐α and sTNF‐R1 with depression and apathy in AD patients, 258,259 suggest that the downregulation of the TNF system induced by Cerebrolysin is relevant for its behavioral effects. In participants of another AD clinical trial, 218 the combination therapy with Cerebrolysin and donepezil reduced serum TNF‐α levels significantly with respect to donepezil; and TNF‐α decreases correlated with improvements in ADL functioning and cognition at study endpoint (Week 28) 260 .…”

Blood plasma protein profiles of neuropsychiatric symptoms and related cognitive decline in older people

“…Some previous studies reported tumor necrosis factor alpha (Guimarães et al, 2013;Ruthirakuhan et al, 2020), homocysteine (Kim & Lee, 2014;Soni et al, 2019), interleukin-6 (Holmes et al, 2011, brain-derived neurotrophic factor (Alvarez et al, 2014;Nagata et al, 2014), clusterin (Mukaetova-Ladinska et al, 2015, and kynurenic acid (Solvang et al, 2019) to be associated with NPS.…”