Effect of Cognitive Reserve Markers on Alzheimer Pathologic Progression

Abstract

Education, occupation, premorbid intelligence and brain size are surrogate markers for cognitive reserve. Whether these markers have biological influence on Alzheimer disease (AD) pathology is not known. We thus aimed to investigate the effect of cognitive reserve proxies on longitudinal change of AD biomarkers. A total of 819 participants with normal cognition (NC), mild cognitive impairment (MCI) and mild AD were enrolled in the Alzheimer’s Disease Neuroimaging Initiative and followed up with repeated measures of CSF, PET and MRI biomarkers. Generalized estimating equations were employed to assess whether biomarker rates of change were modified by reserve proxies. CSF Aβ42 decline was slower in NC participants with higher cognitive reserve indexed by education, occupation and American National Adult Reading Test (ANART). The decline of [18F] fluorodeoxyglucose PET uptake was slower in AD participants with better performance on the ANART. Education, occupation and ANART did not modify the rates of MRI hippocampal atrophy in any group. These findings remained unchanged after accounting for APOE 4, longitudinal missing data and baseline cognitive performance. Higher levels of reserve markers may slow the rate of amyloid deposition before cognitive impairment and preserve glucose metabolism at the dementia stage over the course of AD pathological progression.

Cognitive reserve and neuropsychiatric disorders

“…Higher premorbid IQ, education and occupation were found in one study to be associated with a slower rate of CSF abeta42 decline over 3 years in elderly cognitively normal people [27] but not in another study using similar measures of cognitive reserve over the same time course [23]. Studies examining the effect of life-long engagement with cognitively stimulating activities, rather than education and IQ, have also produced mixed results.…”

“…Longitudinal studies agree that indices of cognitive reserve do not modify the impact of the APOE e4 allele on increased risk of Alzheimer's disease [27,31,32] although one study found that cognitive reserve interacted to enhance the protective effect of the APOE e2 allele [32], an effect in a relative small number of participants that requires replication.…”

Emerging Concepts in Alzheimer's Disease

“…In autopsy brain tissue, PiB appears to bind to SPs immunoreactive for either Aβ 1−42 or Aβ 1−40 and to microvascular amyloid. Progressive hippocampal atrophy can be evaluated by measuring changes in hippocampal volume over time (119). Antemortem imaging of CNS phospho-tau appears to be more difficult, though some studies suggest it can be done using [ 18 F]fluoroethyl-methyl-amino-2-naphthyl-ethylidene malononitrile (FDDNP); studies using this ligand have been performed in subjects with MCI (13).…”

Cognitive functioning, cognitive reserve, and residential care placement in patients with Alzheimer's and related dementias

“…For example, a five-year prospective study of older adults (early-stage AD at intake and normal controls) found faster cortical atrophy in some brain areas of AD patients with higher (more than nine years) education compared with AD patients with lower (nine years or less) education (Cho et al, 2015). Lo and Jagust (2013) examined three lifestyle proxies for cognitive reserve (education, occupation, and premorbid IQ), and found direct associations with several AD biomarkers (cerebrospinal fluid Ab42, fluorodeoxyglucose positron emission tomography uptake); the cognitive reserve proxies slowed pathologic progression particularly in normal controls, suggesting that the protective effect of cognitive reserve (education) may occur mainly before impairment in cognitive functioning is observed.…”