The Modulatory Effect of Cerebrovascular Burden in Response to Cognitive Stimulation in Healthy Ageing and Mild Cognitive Impairment

Abstract

Background. Cerebrovascular burden is a common pathology in mild cognitive impairment (MCI) and Alzheimer’s disease (AD), with an additive impact on cognitive functioning. Despite being proposed as a potential moderator of cholinesterase inhibiting drug therapy, there is a paucity of evidence investigating the impact of cerebrovascular pathology on responsiveness to cognitive interventions. Method. The current study uses neuropsychological, neurostructural, and functional connectivity indices to characterise response to a cognitive stimulation paradigm in 25 healthy ageing and 22 MCI participants, to examine the hypothesised detrimental effects of concurrent vascular pathology. Results. In both healthy ageing and MCI, increased levels of vascular pathology limited the potential for a neuroplastic response to cognitive stimulation. In healthy ageing, participants with lower levels of vascular burden had greater functional connectivity response in the target posterior default mode network. Those with low levels of vascular pathology in the MCI cohort had increased functional connectivity of the right insula and claustrum within the salience network. Burden did not, however, predict cognitive or neuroanatomical changes. Conclusions. The current research evidences the modulatory effect of cerebrovascular pathology in interventions aimed at re-establishing network connectivity to prevent cognitive deterioration and delay the transition to the dementia stage of AD. Examination of co-occurring vascular pathology may improve precision in targeting treatment to MCI candidates who may respond optimally to such cognitive interventions.

Cognitive Interventions: Symptomatic or Disease-Modifying Treatments in the Brain?

“…Accordingly, two studies found that compared to standard care, 8-week CR and 7-week CS programs could improve fMRI even in individuals with mild dementia ( 14 , 15 ). Interestingly, Bentham et al observed that individuals with high vascular burden had a lower functional connectivity response to CS than those with low burden, suggesting that vascular pathology could limit the potential for a neuroplastic response to cognitive interventions ( 16 ).…”

Personalized treatment interventions: nonpharmacological and natural treatment strategies in Alzheimer’s disease

“…While numerous preclinical and clinical trials demonstrated some beneficial effects of different types of physical exercise on AD biomarkers, the data on the effects of cognitive interventions are scarce. Among participants with MCI or healthy elderly people, who participated in computerized cognitive stimulation during 20 sessions, those with the higher vascular burden (regarding the volume of white matter hyperintensities) had a decreased neuroplastic response (assessed as upregulation in functional connectivity within the brain default mode network) to this intervention [49]. In a rat model, physical or cognitive exercise reversed the decrease in hippocampal lipid peroxidation, and restored Aβ infusion-impaired hippocampal AChE activity, and hippocampal tissue disorganization, but did not improve lowered total antioxidant capacity [26].…”

White-Matter Hyperintensity Load and Differences in Resting-State Network Connectivity Based on Mild Cognitive Impairment Subtype

“…The Lesion Growth Algorithm (LGA) function was applied at a threshold of κ = 0.3 and the resulting individual WMH volume, expressed in ml, was divided by its respective TIV to obtain a fractional index of white matter lesion volume. A κ = 0.3 has been indicated as the best performing threshold by an earlier methodological study (Schmidt et al, 2012) and has been used in previous research as the optimal value to separate WMH from normal tissue (De Marco et al, 2017b;Bentham et al, 2019;Manca et al, 2021).…”