NEUROPSYCHIATRIC BURDEN IS RELATED TO INCREASED AMYLOID BUT NOT TAU DEPOSITION IN COGNITIVELY NORMAL OLDER ADULTS

Abstract

Neuropsychiatric factors (NPF; e.g. depression, anxiety, apathy) are highly prevalent in older adults and are associated with an increased risk of Alzheimer's disease (AD) (Masters et al, 2015). Recent evidence also linked personality traits (e.g. neuroticism) with progression to AD (Terracciano et al, 2017). The mechanisms by which personality/NPF burden influence AD risk need to be better understood. In cognitively normal older adults at risk of AD, we investigated whether an index of personality/NPF burden was related to AD pathology (amyloid [Aβ] and tau deposition), brain function and cognition. Eighty-two participants (PREVENT-AD study, age=67±5) answered questionnaires assessing personality, perseverative thinking, depression, anxiety, stress and apathy. They underwent Aβ-PET ([18F]NAV4694), tau-PET ([18F]AV1451), resting-state fMRI and cognitive assessment (Repeatable Battery for Assessment of Neuropsychological Status). PET SUVRs were extracted bilaterally from all FreeSurfer Desikan neocortical regions. We used a multivariate approach (partial least squares correlation with permutation tests) to assess which combination of factors was related to Aβ and tau deposition. We then investigated whether this index of personality/NPF burden was related to 1) functional connectivity and 2) cognitive performance in individuals with and without significant AD pathology. Aβ (p=0.003), but not tau (p>0.05) was related to personality/NPF burden. More specifically, a combination of perseverative thinking, neuroticism and apathy was associated with higher Aβ accumulation, predominantly in the AD-signature regions (Fig.1). Higher scores on this personality/NPF component were additionally associated with higher connectivity within the dorsal attention and salience networks in Aβ+ subjects, and lower connectivity in Aβ- subjects (Aβ-status*connectivity: F1,69=5.7-5.2, p=.02-.03 respectively, Fig.2A). Furthermore, higher scores on this personality/NPF component were associated with worse immediate memory (F1,70=4.1, p=.05, Fig.2B), regardless of Aβ status. Relative importance of personality traits and neuropsychiatrie factors (NPF) in relation to regional Aβ accumulation. IA. Loading of each personality traits and NPF score from the component relating personality/NPF with Aβ burden. Traits and factors contributing the most to the model are perseverative thinking, neuroticism and apathy. Confidence intervals are derived from bootstrap resampling. IB. Cortical regions showing higher Aβ SUVR as personality/NPF burden increases. The importance of each region in the model was identified from bootstrap ratios and projected on a brain template. Personality/NPF relationship with brain function (A) and cognition (B) 2A. Functional networks showing a significant interaction of Aβ status by functional connectivity on the personality/NPF burden. 2B. Relationship between personality/NPF burden and immediate memory performance. Our multivariate approach revealed that Aβ burden was increased in cognitively normal individuals at risk of AD showing high levels of perseverative thinking, neuroticism and apathy, which were in turn related to altered brain connectivity and lower cognition. Overall, these results highlight the importance of personality/NPF burden on early AD pathophysiology.