Cognitive Profile of Amyloid Burden and White Matter Hyperintensities in Cognitively Normal Older Adults

Department of Psychology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 11/2012; 32(46):16233-16242. DOI: 10.1523/JNEUROSCI.2462-12.2012
Source: PubMed


Amyloid burden and white matter hyperintensities (WMH) are two common markers of neurodegeneration present in advanced aging. Each represents a potential early indicator of an age-related neurological disorder that impacts cognition. The presence of amyloid is observed in a substantial subset of cognitively normal older adults, but the literature remains equivocal regarding whether amyloid in nondemented populations is deleterious to cognition. Similarly, WMH are detected in many nondemented older adults and there is a body of evidence indicating that WMH are associated with decreased executive function and other cognitive domains. The current study investigated amyloid burden and WMH in clinically normal older adult humans aged 65-86 (N = 168) and examined each biomarker's relation with cognitive domains of episodic memory, executive function, and speed of processing. Factors for each domain were derived from a neuropsychological battery on a theoretical basis without reference to the relation between cognition and the biomarkers. Amyloid burden and WMH were not correlated with one another. Age was associated with lower performance in all cognitive domains, while higher estimated verbal intelligence was associated with higher performance in all domains. Hypothesis-driven tests revealed that amyloid burden and WMH had distinct cognitive profiles, with amyloid burden having a specific influence on episodic memory and WMH primarily associated with executive function but having broad (but lesser) effects on the other domains. These findings suggest that even before clinical impairment, amyloid burden and WMH likely represent neuropathological cascades with distinct etiologies and dissociable influences on cognition.

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Available from: Dorene Rentz, Dec 16, 2013
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    • "Other brain MRI traits have shown significant associations with particular cognitive domains or in specific demographic groups. WMH, for example, are mainly associated with impaired executive functioning, particularly in ageing populations where WMH are more prevalent (Farias et al., 2012; Gunning-Dixon & Raz, 2000; Hedden et al., 2012). A twin study of older men showed that 70–100% of the correlation between WMH and cognitive traits was due to common genes (Carmelli et al., 2002). "
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    • "Each neuropsychological score was multiplied by the relevant factor weight from the prior report and these weighted scores were summed to compute the factor scores for processing speed, executive function, and memory. To ensure that the factor structure was not meaningfully altered by adding subjects to the prior report , we also conducted a comparison of the factor weightings in the completed baseline HABS sample and the prior sample from Hedden et al. (2012) and found convergence in the factor structure across samples. The executive function factor score was composed of measures of verbal fluency (FAS/CAT; Benton et al., 1994;Monsch et al., 1992 "
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