The potential of functional MRI as a biomarker in early Alzheimer's disease
Open accessAbstract
Functional magnetic resonance imaging (fMRI) is a relative newcomer in the field of biomarkers for Alzheimer's disease (AD). fMRI has several potential advantages, particularly for clinical trials, as it is a noninvasive imaging technique that does not require the injection of contrast agent or radiation exposure and thus can be repeated many times during a longitudinal study. fMRI has relatively high spatial and reasonable temporal resolution, and can be acquired in the same session as structural magnetic resonance imaging. Perhaps most importantly, fMRI may provide useful information about the functional integrity of brain networks supporting memory and other cognitive domains, including the neural correlates of specific behavioral events, such as successful versus failed memory formation.
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As task difficulty increases, neural activity, particularly in frontal regions, tends to increase up to a certain level, beyond which activation asymptotes and ultimately declines.
“As task difficulty increases, neural activity (particularly in frontal regions) tends to increase up to a certain level33, beyond which activation asymptotes and ultimately declines (FIG. 3–A)36,37.”
From Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing (2018) · cites this paper as [36]
The Abstract (page unavailable) reports increased prefrontal activity during task performance in people with Alzheimer’s dementia, but does not relate that activity to increasing task difficulty. The cited paper’s copy does not establish the graded increase or threshold attributed to citation 33; searches for task difficulty, load, and increasing demands found no such passage. (LLM, conf=0.76)
Experimental — accuracy not yet measuredYoung adults may also upregulate activity in response to increased task demands, but the demand threshold for upregulation may be higher in young than in older adults.
“It is worth noting that young adults may also upregulate activity in response to increased task demands, but that the demand threshold for upregulation may be higher in young, compared to older adults24,36.”
From Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing (2018) · cites this paper as [36]
The Abstract discusses increased fMRI activity in people with mild cognitive impairment or at risk of Alzheimer’s disease, but does not compare young and older adults’ responses to increasing task demands. Searches for young adults, task difficulty, and demand thresholds found no passage addressing the proposed difference in upregulation thresholds. (LLM, conf=0.72)
Experimental — accuracy not yet measuredConsistent with reduced neural resources, older adults show a greater increase in activity, a lower asymptote, and an earlier decline than younger adults.
“Several studies36,38–41 have found that, consistent with reduced neural resources, older adults show a greater increase in activity, a lower asymptote, and an earlier decline than younger adults”
From Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing (2018) · cites this paper as [36]
The Abstract discusses increased activation in people at risk for Alzheimer’s disease, followed by loss of activation as cognitive impairment worsens; it does not compare activation patterns in older and younger adults. Searches for “asymptote” and age-related activation under increasing task demand found no passage addressing the claimed lower asymptote or earlier decline. (LLM, conf=0.76)
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References 96 · Cited by 187
- Authors
- Sperling, R.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Sperling, Reisa
- ORCID
- Sperling, Reisa
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 32
- Pages
- S37-S43
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC3233699
- OpenAlex
- W2065331648
- Cited by
- 187
- References
- 96
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 11 · 2023: 14 · 2022: 10 · 2021: 27 · 2020: 11 · 2019: 7 · 2018: 14 · 2017: 16 · 2016: 7 · 2015: 8 · 2014: 10 · 2013: 16 · 2012: 9
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (K24AG035007, P50AG005134, P01AG036694, P30AG062421)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- functional MRI, Alzheimer's disease, biomarkers, early diagnosis, brain networks, memory, longitudinal imaging, clinical trials
- MeSH terms
- Alzheimer Disease, Brain, Cognition, Humans, Magnetic Resonance Imaging, Memory, Risk, Biomarkers
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