Relationship of cognitive reserve and cerebrospinal fluid biomarkers to the emergence of clinical symptoms in preclinical Alzheimer's disease

Abstract

Levels of β-amyloid and phosphorylated tau (p-tau), as measured in cerebrospinal fluid (CSF), have been associated with risk of progressing from normal cognition to onset of clinical symptoms during preclinical Alzheimer’s disease (AD). We examined whether cognitive reserve (CR) modifies this association. CSF was obtained at baseline from 239 participants (mean age 57.2 years) who had been followed for up to 17 years with clinical and cognitive assessments (mean follow-up 8 years). A composite score based on the National Adult Reading Test (NART), vocabulary, and years of education at baseline was used as an index of CR. Cox regression models showed that increased risk of progressing from normal cognition to symptom onset was associated with lower CR, lower baseline β-amyloid, and higher baseline p-tau. There was no interaction between CR and β-amyloid, suggesting that the protective effects of higher CR are equivalent across the observed range of amyloid levels. By contrast, both tau and p-tau interacted with CR, indicating that CR was more protective at lower levels of tau and p-tau.

Cognitive reserve and neuropsychiatric disorders

“…Longitudinal studies have found that more years of education and higher premorbid IQ are associated with a later onset of dementia symptoms [21][22][23] and, following onset, cognitive decline is faster in those with these indices of higher cognitive reserve [22]. The latter phenomenon has been hypothesised to reflect increasing neuropathological load eventually overriding the protective effect of cognitive reserve.…”

Cognitive reserve: the evolution of the conceptual framework

“…On the contrary, individuals with low genetic AD risk and high CR levels better withstand AD pathology and, therefore, maintain longer normal cognitive functions. An interaction between CR, tau and phosphorylated tau (p-tau), but not β-amyloid levels, was demonstrated [37]. However, also an additive, rather than interacting, effect was reported for CR levels and AD biomarkers [39].…”

“…Previous studies showed several significant interaction effects between levels of CR, CSF-biomarkers (β-amyloid and tau levels), genetic AD-like phenotype (APOE status), brain atrophy and the risk to develop the clinical symptoms of AD [27,[35][36][37][38]. In particular, Jack and co-workers [35] showed that people with a high risk of cognitive impairment due to AD pathophysiological processes, have both APOE 4 and low CR levels.…”

Neural Correlates of Brain Reserve: A Neuroimaging Perspective

“…APOE, b-amyloid levels, brain atrophy, etc.) and the risk to develop the clinical symptoms of AD (Jack et al 2013;Serra et al 2011Serra et al , 2015Soldan et al 2013;Bozzali et al 2014).…”

“…On the contrary, individuals with low genetic AD risk and high CR levels better withstand AD pathology and, therefore, maintain longer normal (2015) cognitive functions. Recently, an interaction between CR, tau and phosphorylated tau (p-tau), but not b-amyloid levels, was demonstrated (Soldan et al 2013). However, also an additive, rather than interacting, effect was reported for CR levels and AD biomarkers (Vemuri et al 2011).…”