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Brain characteristics of memory decline and stability in aging: Contributions from longitudinal observations
Stockholm University, Faculty of Social Sciences, Department of Psychology.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Aging is typically associated with declining mental abilities, most prominent for some forms of memory. There are, however, large inter-individual differences within the older population. Some people experience rapid decline whereas others seem almost spared from any adverse effects of aging. This thesis examined the neural underpinnings of such individual differences by using longitudinal observations of episodic memory change across 15-20 years, combined with structural and functional magnetic resonance imaging of the brain. Study I found significant correlations between volume and activity of the hippocampus (HC), and memory change over a 6-year period. That is, individuals with decline in HC function also had declining memory. In contrast, Study II showed that successfully aged individuals, who maintained high memory scores over 15-20 years, had preserved HC function compared to age-matched elderly with average memory change. The successful agers had HC activity levels comparable to those of young individuals, as well as higher frontal activity. Study III revealed that individual differences in memory ability and brain activity of elderly reflect both differential age-related changes, and individual differences in memory ability that are present already in midlife, when age effects are minimal. Specifically, memory scores obtained 15-20 years earlier reliably predicted brain activity in memory-relevant regions such as the frontal cortex and HC. This observation challenges results from previous cross-sectional aging studies that did not consider individual differences in cognitive ability from youth. Collectively the three studies implicate HC and frontal cortex function behind heterogeneity in cognitive aging, both substantiating and qualifying previous results from cross-sectional studies. More generally, the findings highlight the importance of longitudinal estimates of cognitive change for fully understanding the mechanisms of neurocognitive aging.

Place, publisher, year, edition, pages
Stockholm: Department of Psychology, Stockholm University , 2013. , 114 p.
Keyword [en]
aging, episodic memory, individual differences, longitudinal assessment, magnetic resonance imaging, hippocampus, frontal cortex
National Category
Psychology (excluding Applied Psychology)
Research subject
Psychology
Identifiers
URN: urn:nbn:se:su:diva-93026ISBN: 978-91-7447-734-4 (print)OAI: oai:DiVA.org:su-93026DiVA: diva2:643871
Public defence
2013-10-04, David Magnussonsalen (U31), Frescati Hagväg 8, Stockholm, 13:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.

Available from: 2013-09-12 Created: 2013-08-28 Last updated: 2013-09-12Bibliographically approved
List of papers
1. Longitudinal structure – function correlates in elderly reveal MTL dysfunction with cognitive decline
Open this publication in new window or tab >>Longitudinal structure – function correlates in elderly reveal MTL dysfunction with cognitive decline
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2012 (English)In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 22, no 10, 2297-2304 p.Article in journal (Refereed) Published
Abstract [en]

By integrating behavioral measures and imaging data, previous investigations have explored the relationship between biological markers of aging and cognitive functions. Evidence from functional and structural neuroimaging has revealed that hippocampal volume and activation patterns in the medial temporal lobe (MTL) may predict cognitive performance in old age. Most past demonstrations of age-related differences in brain structure–function were based on cross-sectional comparisons. Here, the relationship between 6-year intraindividual change in functional magnetic resonance imaging (fMRI) signal and change in memory performance over 2 decades was examined. Correlations between intraindividual change in fMRI signal during episodic encoding and change in memory performance measured outside of scanning were used as an estimate for relating brain–behavior changes. The results revealed a positive relationship between activation change in the hippocampus (HC) and change in memory performance, reflecting reduced hippocampal activation in participants with declining performance. Using a similar analytic approach as for the functional data, we found that individuals with declining performance had reduced HC volume compared with individuals with intact performance. These observations provide a strong link between cognitive change in older adults and MTL structure and function and thus provide insights into brain correlates of individual variability in aging trajectories.

Keyword
fMRI, aging, memory, hippocampus, longitudinal
National Category
Psychology Neurosciences Radiology, Nuclear Medicine and Medical Imaging
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-80902 (URN)10.1093/cercor/bhr306 (DOI)000308530500008 ()
Available from: 2012-10-02 Created: 2012-10-02 Last updated: 2017-12-07Bibliographically approved
2. Brain characteristics of individuals resisting age-related cognitive decline over two decades
Open this publication in new window or tab >>Brain characteristics of individuals resisting age-related cognitive decline over two decades
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2013 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 33, no 20, 8668-8677 p.Article in journal (Refereed) Published
Abstract [en]

Some elderly appear to resist age-related decline in cognitive functions, but the neural correlates of successful cognitive aging are not well known. Here, older human participants from a longitudinal study were classified as successful or average relative to the mean attrition-corrected cognitive development across 15-20 years in a population-based sample (n = 1561). Fifty-one successful elderly and 51 age-matched average elderly (mean age: 68.8 years) underwent functional magnetic resonance imaging while performing an episodic memory face-name paired-associates task. Successful older participants had higher BOLD signal during encoding than average participants, notably in the bilateral PFC and the left hippocampus (HC). The HC activation of the average, but not the successful, older group was lower than that of a young reference group (n = 45, mean age: 35.3 years). HC activation was correlated with task performance, thus likely contributing to the superior memory performance of successful older participants. The frontal BOLD response pattern might reflect individual differences present from young age. Additional analyses confirmed that both the initial cognitive level and the slope of cognitive change across the longitudinal measurement period contributed to the observed group differences in BOLD signal. Further, the differences between the older groups could not be accounted for by differences in brain structure. The current results suggest that one mechanism behind successful cognitive aging might be preservation of HC function combined with a high frontal responsivity. These findings highlight sources for heterogeneity in cognitive aging and may hold useful information for cognitive intervention studies.

National Category
Neurosciences
Identifiers
urn:nbn:se:su:diva-91525 (URN)10.1523/JNEUROSCI.2900-12.2013 (DOI)000319112600009 ()
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Note

AuthorCount:6;

Available from: 2013-07-01 Created: 2013-06-28 Last updated: 2017-12-06Bibliographically approved
3. Midlife memory ability accounts for brain activity differences in healthy aging
Open this publication in new window or tab >>Midlife memory ability accounts for brain activity differences in healthy aging
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Cross-sectional neuroimaging studies suggest that hippocampal and prefrontal cortex (PFC) functions underlie individual differences in memory ability in elderly individuals, but it is unclear how individual differences in cognitive ability in youth contribute to cognitive and neuroimaging measures in older age. Here, a sample from a longitudinal population-based study (N = 201, aged 55-80) was used to investigate the relative influence of midlife memory ability and age-related memory change on memory-related BOLD-signal variability in healthy elderly. Hierarchical regression analyses showed that midlife memory ability, assessed 15-20 years earlier, explained at least as much variance as memory change in clusters in the left inferior PFC and the bilateral hippocampus, during memory encoding. Memory change estimates, however, were found to be more sensitive in detecting bilateral frontal regions specifically diagnostic of age-related memory change. These finding highlight challenges in interpreting individual differences in neurocognitive measures as age-related changes in the absence of longitudinal data, and also demonstrates the improved sensitivity of longitudinal measures.

Keyword
cognitive aging; individual differences; fMRI; episodic memory; longitudinal assessment
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:su:diva-93025 (URN)
Funder
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Available from: 2013-08-28 Created: 2013-08-28 Last updated: 2013-08-29

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