Static and Dynamic Cognitive Reserve Proxy Measures: Interactions with Alzheimer's Disease Neuropathology and Cognition.

OBJECTIVE: Years of education are the most common proxy for measuring cognitive reserve (CR) when assessing the relationship between Alzheimer's disease (AD) neuropathology and cognition. However, years of education may be limited as a CR proxy given that it represents a specific timeframe in early life and is static. Studies suggest that measures of intellectual function provide a dynamic estimate of CR that is superior to years of education since it captures the effect of continued learning over time. The present study determined whether dynamic measures of CR were better predictors of episodic memory and executive function in the presence of AD pathology than a static measure of CR. METHODS: Subjects examined died with a pre-mortem clinical diagnosis of no cognitive impaired, mild cognitive impairment and mild to moderate AD. CERAD and Braak stage were used to stratify the sample by AD pathology severity. Linear regression analyses using CR by CERAD and CR by Braak stage interaction terms were used to determine whether Extended Range Vocabulary Test (ERVT) scores or years of education were significantly associated with episodic memory composite (EMC) and executive function composite (EFC) performance. All models were adjusted for clinical diagnosis, age at death, gender, APOE e4 carrier status and Braak stage. RESULTS: For episodic memory, years of education by CERAD interaction were not statistically significant (ß=-0.01, SE=0.01, p=0.53). By contrast, ERVT interaction with CERAD diagnosis was statistically significant (ß=-0.03, SE=0.01, p=0.004). Among the models using Braak stages, none of the CR by pathology interactions were associated with EMC or EFC. CONCLUSION: Results suggest that a dynamic rather than a static measure is a better indicator of CR and that the relationship between CR and cognition is dependent upon the severity of select AD criteria.

Cognitive Domain Dispersion Association with Alzheimer's Disease Pathology.

Within neuropsychology, the term dispersion refers to the degree of variation in performance between different cognitive domains for an individual. Previous studies have demonstrated that cognitively normal individuals with higher dispersion are at an increased risk for progressing to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Therefore, we determined 1) whether increased dispersion in older adults was associated with amyloid plaques and neurofibrillary tangles (NFTs) and 2) whether increased cognitive dispersion accurately differentiated MCI and AD from non-cognitively impaired (NCI) individuals. The intra-subject standard deviation (ISD) was used to quantify cognitive dispersion, and receiver operator characteristic (ROC) analysis determined whether ISD differentiated MCI and AD from NCI. Neuropathological scores for diffuse plaques (DPs), neuritic plaques (NPs), and NFTs were used as outcome measures in a series of negative binomial regression models. Regression analyses found that increased ISD was associated with increased NFT pathology (ß= 10.93, SE = 3.82, p = 0.004), but not with DPs (ß= 1.33, SE = 8.85, p = 0.88) or NPs (ß= 14.64, SE = 8.45, p = 0.08) after adjusting for age at death, gender, education, APOE ɛ4 status, and clinical diagnosis. An interaction term of ISD with age at death also showed a significant negative association (ß= -0.13, SE = 0.04, p = 0.004), revealing an age-dependent association between ISD with NFTs. The ISD failed to show an acceptable level of diagnostic accuracy for MCI (AUC = 0.60). These findings suggest that increased cognitive dispersion is related to NFT pathology where age significantly affects this association.