Comparison of Semantic and Episodic Memory BOLD fMRI Activation in Predicting Cognitive Decline in Older Adults

Hantke, Nathan; Nielson, Kristy A.; Woodard, John L.; Breting, Leslie M. Guidotti; Butts, Alissa M.; Seidenberg, Michael; Smith, J. Carson; Durgerian, Sally; Lancaster, Melissa A.; Matthews, Monica; Sugarman, Michael A.; Rao, Stephen M.

doi:10.1017/s1355617712000951

Cited by 22 publications

(25 citation statements)

References 55 publications

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“…Removing incorrect trials does not entirely correct the problem because the resulting brain maps are generated from a sparse number of correct trials in individuals performing near chance. Moreover, the BOLD signals that result from greater task difficulty or effort in the poor performing group will be inseparable from activation related to memory retrieval-related processes, thus confounding any sound interpretation of the activation maps (Hantke et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

Genetic risk for Alzheimer's disease alters the five-year trajectory of semantic memory activation in cognitively intact elders

et al. 2015

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Healthy aging is associated with cognitive declines typically accompanied by increased task-related brain activity in comparison to younger counterparts. The Scaffolding Theory of Aging and Cognition (STAC) (Park and Reuter-Lorenz, 2009; Reuter-Lorenz and Park, 2014) posits that compensatory brain processes are responsible for maintaining normal cognitive performance in older adults, despite accumulation of aging-related neural damage. Cross-sectional studies indicate that cognitively intact elders at genetic risk for Alzheimer’s disease (AD) demonstrate patterns of increased brain activity compared to low risk elders, suggesting that compensation represents an early response to AD-associated pathology. Whether this compensatory response persists or declines with the onset of cognitive impairment can only be addressed using a longitudinal design. The current prospective, 5-year longitudinal study examined brain activation in APOE ε4 carriers (N=24) and non-carriers (N=21). All participants, ages 65–85 and cognitively intact at study entry, underwent task-activated fMRI, structural MRI, and neuropsychological assessments at baseline, 18, and 57 months. fMRI activation was measured in response to a semantic memory task requiring participants to discriminate famous from non-famous names. Results indicated that the trajectory of change in brain activation while performing this semantic memory task differed between APOE ε4 carriers and non-carriers. The APOE ε4 group exhibited greater activation than the Low Risk group at baseline, but they subsequently showed a progressive decline in activation during the follow-up periods with corresponding emergence of episodic memory loss and hippocampal atrophy. In contrast, the non-carriers demonstrated a gradual increase in activation over the 5-year period. Our results are consistent with the STAC model by demonstrating that compensation varies with the severity of underlying neural damage and can be exhausted with the onset of cognitive symptoms and increased structural brain pathology. Our fMRI results could not be attributed to changes in task performance, group differences in cerebral perfusion, or regional cortical atrophy.

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Section: Discussionmentioning

confidence: 99%

Genetic risk for Alzheimer's disease alters the five-year trajectory of semantic memory activation in cognitively intact elders

et al. 2015

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“…Although there are multiple hereditary factors associated with AD, the apolipoprotein-E (APOE) ε4 allele is a well-recognized, important risk factor for AD that is also associated with familial clustering (e.g., Saunders et al, 1993aSaunders et al, , 1993b. Furthermore, its presence has been associated with differential brain activity patterns, including in the frontal lobes, in studies with cognitively intact elders (e.g., Hantke et al, 2013;Seidenberg et al, 2013;Smith et al, 2014) and the literature as a whole supports a robust negative effect of APOE ε4 on multiple domains of cognition in healthy elders, including executive functioning (Wisdom, Callahan, & Hawkins, 2011).…”

Section: Neuropsychologymentioning

confidence: 99%

Executive functioning and risk for Alzheimer’s disease in the cognitively intact: Family history predicts Wisconsin Card Sorting Test performance.

Hazlett¹,

Figueroa²,

Nielson³

2015

Neuropsychology

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Objective: Alzheimer's disease (AD) research typically focuses on memory. However, executive functioning (EF) deficits are also common among AD patients; these deficits are associated with decreased functioning in activities of daily living, an important criterion in diagnosing AD. A classic test of EF ability, the Wisconsin Card Sort Test (WCST), has demonstrated sensitivity to differentiating individuals with AD from healthy controls, discriminating AD groups based on disease severity, and distinguishing AD from other types of dementia. Such sensitivity to AD raises the possibility that the WCST is also sensitive to very early, preclinical differences between those who have heightened risk for AD and those with lower risks. Method: The current study, therefore, examined WCST performance in healthy, cognitively intact older adults with a first-degree (i.e., sibling or parent) family history (FH) of AD (n ϭ 18) and those with no such FH of AD (n ϭ 24). Results: Results revealed significant group differences for Categories Achieved, Percent Conceptual Level Responses, Total Errors, Perseverative Errors, and Non-Perseverative Errors, with the FH ϩ group consistently exhibiting poorer performance. Moreover, hierarchical regression analyses indicated that after accounting for age, sex, and education, FH significantly predicted all 5 of these variables. Conclusions: These results speak to the potential role of EF in bolstering the current understanding of early cognitive markers of future decline. Furthering what is known about the relationship between AD and nonmemory specific domains of cognition such as executive functioning may allow for better prediction of cognitive decline and potential progression to AD.

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“…Rather, our definition of cognitive decline was purposely liberal in order to examine elders who are in the very early stages of cognitive decline and exhibit subtle but meaningful changes in cognitive performance. Even though the decline may not be at a clinically significant level, our previous work, using the same criteria and follow-up period as the current study, has shown that declining elders have smaller hippocampal volumes at baseline, differential patterns of fMRI activation in response to semantic and episodic memory tasks at baseline, and are more likely to carry the APOE ε4 allele (Hantke et al, 2013; Seidenberg et al, 2013; Woodard et al, 2010; Woodard et al, 2012). The current work serves to add to this literature by demonstrating that IIV can also serve as a prognostic indicator of future cognitive decline.…”

Section: Discussionmentioning

confidence: 58%

Performance variability during a multitrial list-learning task as a predictor of future cognitive decline in healthy elders

Sugarman

Woodard

Nielson

et al. 2014

Journal of Clinical and Experimental Neuropsychology

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Introduction In clinical settings, neuropsychological test performance is traditionally evaluated with total summary scores (TSS). However, recent studies demonstrated that indices of intraindividual variability (IIV) yielded unique information complementing TSS. This 18-month longitudinal study sought to determine whether IIV indices derived from a multitrial list-learning test (the Rey Auditory Verbal Learning Test) provided incremental utility in predicting cognitive decline in older adults compared to TSS. Method Ninety-nine cognitively intact older adults (aged 65 to 89 years) underwent neuropsychological testing (including the Rey Auditory Verbal Learning Test) at baseline and 18-month follow-up. Participants were classified as cognitively stable (n = 65) or declining (n = 34) based on changes in their neuropsychological test performance. Logistic regression modeling tested the ability of baseline TSS indices (Sum of Trials 1-5, Immediate Recall, and Delayed Recall) and IIV indices (Lost Access and Gained Access) to discriminate between stable and declining individuals. Results Higher values of both Lost Access and Gained Access at baseline were associated with an increased risk for decline at 18-month follow-up. Further, the IIV indices provided predictive utility above and beyond the TSS indices. Conclusion These results highlight the value of analyzing IIV in addition to TSS during neuropsychological evaluation in older adults. High levels of IIV may reflect impairment in anterograde memory systems and/or executive dysfunction that may serve as a prognostic indicator of cognitive decline.

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Comparison of Semantic and Episodic Memory BOLD fMRI Activation in Predicting Cognitive Decline in Older Adults

Cited by 22 publications

References 55 publications

Genetic risk for Alzheimer's disease alters the five-year trajectory of semantic memory activation in cognitively intact elders

Genetic risk for Alzheimer's disease alters the five-year trajectory of semantic memory activation in cognitively intact elders

Executive functioning and risk for Alzheimer’s disease in the cognitively intact: Family history predicts Wisconsin Card Sorting Test performance.

Performance variability during a multitrial list-learning task as a predictor of future cognitive decline in healthy elders

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