Neural Correlates of Mild Behavioral Impairment in older adults across the neurodegenerative spectrum
Authors: Rashidi‐Ranjbar Neda , Churchill Nathan W , Black Sandra E. , Kumar Sanjeev , Tartaglia Carmela , Freedman Morris , Lang Anthony E , Steeves Thomas , Swartz Richard H. , Saposnik Gustavo , Kwan Donna , McLaughlin Paula , Troyer Angela , Symons Sean , Strother Stephen C. , Borrie Michael , Frank Andrew R , Pasternak Stephen H , Pollock Bruce G. , Rajji Tarek K. , Seitz Dallas , Tang‐Wai David F. , Casaubon Leanne , Mandzia Jennifer , Jog Mandar , Masellis Mario , Scott Christopher J. M. , Adamo Sabrina M. , Ozzoude Miracle , Ismail Zahinoor , Munoz David G. , Dowlatshahi Dar , Hassan Ayman , Marras Connie , Bartha Robert , Ramirez Joel , Berezuk Courtney , Holmes Melissa F. , Sahlas Demetrios J. , Southwell Alisia , Arnott Stephen R. , Grimes David A. , Schweizer Tom A. , Fischer Corinne E. 
Published: December 2023

Background

Mild behavioral impairment (MBI) is a syndrome characterized by later life onset, persistent neuropsychiatric symptoms (NPS) in non‐demented older adults. MBI can co‐occur with Mild Cognitive Impairment (MCI) and has a range of neurodegenerative etiologies including Alzheimer’s disease (AD), Cerebrovascular Disease (CVD), and Parkinson’s disease (PD). MBI is associated with poorer cognitive and psychosocial function and an increased risk of developing dementia. Thus, we aimed to explore the structural neural correlates of MBI, specifically in the regions known to be associated with cognitive impairment (i.e., corticolimbic and frontal‐executive circuits), across multiple neurodegenerative diagnoses from the Ontario Neurodegenerative Disease Research Initiative (ONDRI).

Method

We assessed the association between MBI and brain structural alterations via T1‐weighted imaging in three groups with Montreal Cognitive Assessment scores ³19: individuals with MCI (due to AD; n = 37), CVD (n = 129), and PD (n = 127). NPS scores were derived from the Neuropsychiatric Inventory (NPI‐Q) domains, and categorized as NPS+ (i.e., NPI score>0); and NPS‐ (NPI score = 0). We selected regions of interest from the corticolimbic and frontal‐executive circuits to measure brain structure using cortical thickness and subcortical volume. Partial correlation, corrected for age, sex, and education was used to assess the association between MBI and brain structural alterations.

Result

Overall, apathy, depression, and anxiety, which map to the decreased motivation and emotional dysregulation MBI domains, had a high prevalence across all the groups. In the brain‐MBI association analysis, apathy was associated with decreased thickness of the l‐rostral middle frontal, r‐superior temporal, and frontal pole in the PD and CVD (but not MCI) groups. Anxiety was associated with decreased volume of the right hippocampus and amygdala in the MCI group, but not CVD or PD (FDR p< 0.05). No structural correlates were found for depression.

Conclusion

Our findings provide evidence of a specific association between apathy and reduced efficiency of the frontal‐executive system in individuals with PD and CVD. In addition, the well‐established AD corticolimbic atrophy patterns (e.g., hippocampus and amygdala) seen in MCI are prominent in the presence of anxiety. Overall, the relatively distinct brain‐MBI associations across neurodegenerative disorders suggest that pathological substrates may alter MBI neural correlates.