Brain Structural and Amyloid Correlates of Recovery From Semantic Interference in Cognitively Normal Individuals With or Without Family History of Late-Onset Alzheimer’s Disease

Abstract

Failure to recover from proactive semantic interference (frPSI) has been shown to be more sensitive than traditional cognitive measures in different populations with preclinical Alzheimer's disease. The authors sought to characterize the structural and amyloid in vivo correlates of frPSI in cognitively normal offspring of patients with late-onset Alzheimer's disease (O-LOAD), compared with individuals without a family history of neurodegenerative disorders (CS). The authors evaluated the LASSI-L, a test tapping frPSI and other types of semantic interference and delayed recall on the RAVLT, along with 3-T MRI volumetry and positron emission tomography Pittsburgh compound B, in 27 O-LOAD and 18 CS with equivalent age, sex, years of education, ethnicity, premorbid intelligence, and mood symptoms. Recovery from proactive semantic interference (frPSI) and RAVLT delayed recall were lower in O-LOAD cases.Structural correlates of both cognitive dimensions were different in CS and O-LOAD, involving brain regions concerned with autonomic, motor, and motivational control in the former, and regions traditionally implicated in Alzheimer's disease in the latter. Better recovery from retroactive semantic interference was associated with less amyloid load in the left temporal lobe in O-LOAD but not CS. In middle-aged cognitively normal individuals with one parent affected with LOAD, frPSI was impaired compared with persons without a family history of LOAD. The neuroimaging correlates of such cognitive measure in those with one parent with LOAD involve Alzheimer's-relevant brain regions even at a relatively young age.

Individual cognitive and depressive traits associated with maternal versus paternal family history of Late-onset Alzheimer’s disease: Proactive semantic interference versus standard neuropsychological assessments

“…Specifically, the second cued recall for both List A and List B were the strongest predictors of aMCI in logistic regression models and had a greater discriminatory power relative to delayed memory for passages, suggesting that evaluating semantic interference may be more powerful in detecting early features of Alzheimer's disease compared to other evaluations [21]. Other studies have found equivalent yet subtler semantic interference difficulties in asymptomatic middle-aged offspring of patients with Alzheimer's disease and such reduced performance was associated to structural changes in AD-relevant regions, increased amyloid load in the temporal lobe [41] and also exhibited inverse correlations with functional connectivity in limbic regions [42], providing evidence that deficits in semantic interference may represent ( * ) Indicates a significant difference of p < .05 between controls and one group of participants with a family history of Alzheimer's disease. structural and limbic circuit dysfunction in early pathophysiology of Alzheimer's disease and that the LASSI-L should therefore be especially sensitive to subtle cognitive impairments in individuals with a family history of the disease.…”

Regional hyperperfusion in older adults with objectively-defined subtle cognitive decline

“…1,2 Neuropsychological process scores, for example, can be used to detect the cognitive inefficiencies associated with AD, prior to the onset of dementia. 2–6 Process scores quantify the number and types of errors that an individual may make on a neuropsychological test or the approach and strategies that are used on a task. 7 These scores are distinct from the traditionally used overall total score and are often used to understand the cognitive profile of underlying brain pathology.…”

White matter fiber density abnormalities in cognitively normal adults at risk for late-onset Alzheimer's disease

“…In particular, we observed in a sample of offspring of LOAD patients (O-LOAD) that functional connectivity was related to subtle cognitive alterations in episodic memory and the capacity to recover from semantic interference effects during learning when compared to healthy control subjects (CS) (Sánchez et al, 2017). This latter capacity also correlated with brain structure, involving brain regions responsible for autonomic, motor, and motivational control in CS, and regions traditionally implicated in AD in O-LOAD (Abulafia et al, 2018). We also identified isocortical thinning in AD-relevant areas including posterior cingulate, precuneus, and areas of the prefrontal and temporoparietal cortex (Duarte-Abritta et al, 2018).…”

“…Family history increases the risk of developing LOAD (Bertram et al, 2010;Mosconi et al, 2010), and is second only to high age as an epidemiological risk factor. As published previously, persons who are at risk of developing LOAD because of their family history, which can be in part demonstrated by possession of the apolipoprotein E (APOE) ε4 allele, show altered functional and anatomical connectivities (Bendlin et al, 2010;Sánchez et al, 2017;Sheline and Raichle, 2013;Sheng et al, 2017), changes in cognitive variables (Abulafia et al, 2018;Ballard and O'Sullivan, 2013;Loewenstein et al, 2016;Rapp and Reischies, 2005;Reinvang et al, 2012), and abnormal brain structure (Duarte-Abritta et al, 2018;During et al, 2011;Mosconi et al, 2014Mosconi et al, , 2013Reiman et al, 2005). In particular, we observed in a sample of offspring of LOAD patients (O-LOAD) that functional connectivity was related to subtle cognitive alterations in episodic memory and the capacity to recover from semantic interference effects during learning when compared to healthy control subjects (CS) (Sánchez et al, 2017).…”

“…In the present study, we hypothesized that our sample of 23 cognitively normal, middle-aged (40-60 years) O-LOAD have decreased WM microstructure compared to CS (n=22) without a family history of LOAD. In addition, we tested the hypothesis that FBA could reveal changes of WM integrity in O-LOAD and that such changes would be associated with alterations in gray matter (GM) and clinical cognitive performance (Abulafia et al, 2018;Duarte-Abritta et al, 2018).…”