Structure--Function Correlates of Cognitive Decline in Aging

Department of Psychology, Stockholm University, Tukholma, Stockholm, Sweden
Cerebral Cortex (Impact Factor: 8.67). 08/2006; 16(7):907-15. DOI: 10.1093/cercor/bhj036
Source: PubMed


To explore neural correlates of cognitive decline in aging, we used longitudinal behavioral data to identify two groups of older adults (n = 40) that differed with regard to whether their performance on tests of episodic memory remained stable or declined over a decade. Analysis of structural and diffusion tensor imaging (DTI) revealed a heterogeneous set of differences associated with cognitive decline. Manual tracing of hippocampal volume showed significant reduction in those older adults with a declining memory performance as did DTI-measured fractional anisotropy in the anterior corpus callosum. Functional magnetic resonance imaging during incidental episodic encoding revealed increased activation in left prefrontal cortex for both groups and additional right prefrontal activation for the elderly subjects with the greatest decline in memory performance. Moreover, mean DTI measures in the anterior corpus callosum correlated negatively with activation in right prefrontal cortex. These results demonstrate that cognitive decline is associated with differences in the structure as well as function of the aging brain, and suggest that increased activation is either caused by structural disruption or is a compensatory response to such disruption.

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Available from: Jonas Persson, Oct 09, 2015
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    • "Instead the successful encoding contrasts were overall enhanced in the PFC in the ASD group, and signal changes in this region demonstrated a robust inverse relation with the number of category relations in to-be-remembered word triads. Increases in prefrontal activity during memory formation have also been observed in the elderly [Miller et al., 2008; Presson et al., 2006], where they are thought to reflect the engagement of more effortful encoding processes that compensate for age-related structural and/or functional declines in memory networks. Structural and functional PFC abnormalities are widely reported in the ASD literature [e.g., Duerden, Mak-Fan, Taylor, & Roberts, 2012] and behaviorally some parallels have been noted between the memory profile seen in ASD and that seen in older adults [see Bowler & Gaigg, 2008] and patients with frontal lobe pathology [e.g., Bowler et al.2014, 2010; Steele et al.2014, 2007]. "
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    ABSTRACT: Memory functioning in Autism Spectrum Disorder (ASD) is characterized by impairments in the encoding of relational but not item information and difficulties in the recollection of contextually rich episodic memories but not in the retrieval of relatively context-free memories through processes of familiarity. The neural underpinnings of this profile and the extent to which encoding difficulties contribute to retrieval difficulties in ASD remain unclear. Using a paradigm developed by Addis and McAndrews [2006; Neuroimage, 33, 1194–1206] we asked adults with and without a diagnosis of ASD to study word-triplets during functional Magnetic Resonance Imaging (fMRI) scanning that varied in the number of category relations amongst component words. Performance at test confirmed attenuated recollection in the context of preserved familiarity based retrieval in ASD. The results also showed that recollection but not familiarity based retrieval increases as a function of category relations in word triads for both groups, indicating a close link between the encoding of relational information and recollection. This link was further supported by the imaging results, where blood oxygen level dependent (BOLD) signal responses in overlapping regions of the inferior prefrontal cortex were sensitive to the relational encoding manipulation as well as the contrast between recollection versus familiarity based retrieval. Interestingly, however, there was no evidence of prefrontal signal differentiation for this latter contrast in the ASD group for whom signal changes in a left hippocampal region were also marginally attenuated. Together, these observations suggest that attenuated levels of episodic recollection in ASD are, at least in part, attributable to anomalies in relational encoding processes. Autism Res 2015. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    Autism Research 01/2015; 8(3). DOI:10.1002/aur.1448 · 4.33 Impact Factor
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    • "Cognitive aging is characterized by marked inter-individual differences, with 40 –50% of aged individuals showing no deficits on a range of cognitive functions. This has been found in aged people (Borghesani et al., 2012; Glisky, Rubin, & Davidson, 2001; Persson et al., 2006; Schupf et al., 2004; Walhovd et al., 2006; Willis & Schaie, 1986), as well as in aged rodents (Gallagher, Burwell, & Burchinal, 1993; Lee et al., 1994; Pawlowski et al., 2009). Heritability of general cognitive ability increases with age (McClearn et al., 1997; McGue & Christensen, 2001; Schupf et al., 2004), reaching 62% in 80-year-old twins (McClearn et al., 1997). "
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    ABSTRACT: We hypothesized that normal variation in genes influencing the bioavailability of dopamine in prefrontal cortex contribute to inter-individual differences in working memory (WM), particularly in healthy old age. To test this, 858 healthy young, middle-aged, and older people were tested on a spatial WM task and genotyped for catechol-O-methyltransferase (COMT VAL158MET) and dopamine betahydroxylase (DBH; C-1021T) single nucleotide polymorphisms (SNPs). Since these genes encode enzymes influencing levels of extracellular dopamine, important for WM, we reasoned that individuals with low activity alleles of each SNP (less efficient degradation of dopamine by COMT and less efficient conversion of dopamine to norepinephrine by DBH) would have higher levels of extracellular dopamine and therefore better WM performance. We predicted the poorest WM performance in people who are both COMT VAL/VAL and DBH C/C homozygotes, encoding enzymes with high activity. That prediction was borne out, but only in the older group under difficult discrimination. This suggests the high activity alleles of these 2 genes combine in reducing ability to manipulate information in WM among the old. Further, we predicted the best performance in people who inherited both low activity alleles. That prediction was not borne out. That we found genetic effects only among older people and not in midlife indicates that brain changes late in life heighten negative effects of chronically lower levels of extracellular dopamine due to normal genetic variation. We found that age increased the combined effect on WM of the COMT and DBH genes encoding enzymes controlling levels of extracellular dopamine. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Psychology and Aging 06/2014; 29(2):363-373. DOI:10.1037/a0036109 · 2.73 Impact Factor
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    • "When ICV was used for correction (using a covariance method similar to the one specified for height) no substantive differences in the pattern of results were observed. Therefore, in keeping with our previous work (Lind et al., 2006a; Persson et al., 2006) we present the result from the heightcorrected measures. "
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    Neurobiology of aging 03/2014; 35(9). DOI:10.1016/j.neurobiolaging.2014.03.012 · 5.01 Impact Factor
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