Brain structural alterations before mild cognitive impairment
Abstract
OBJECTIVE: To determine whether alterations of brain structure in normal aged individuals precede the development of mild cognitive impairment (MCI) or Alzheimer disease (AD). BACKGROUND: Persons with MCI and AD demonstrate cortical volume losses vs asymptomatic aged individuals, particularly in the hippocampus, amygdala, and entorhinal cortex. It is unknown whether these losses or other volumetric changes are present, and to what degree, in cognitively normal individuals before the clinical diagnosis of MCI. METHODS: Structural MRI was performed on a cross-section of 136 longitudinally examined normal aged subjects. All subjects were cognitively normal at the time of their scan, but 23 later developed MCI, and 9 of these 23 went on to an AD diagnosis. Extracted volumes from voxel-based morphometric analysis were combined with clinical data to compare the 23 subjects who eventually developed MCI to 113 subjects who remained cognitively normal over an average follow-up of 5.4 years. RESULTS: Initially normal subjects who eventually developed MCI demonstrated decreased gray matter volumes in the anteromedial temporal lobes bilaterally and left angular gyrus while still cognitively normal. CONCLUSION: Structural brain changes in anatomic areas involved in higher cognitive processes precede clinical signs and symptoms in longitudinally followed normal subjects destined to develop mild cognitive impairment.
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AβPs and NFTs are present well over a decade before death.
“The interval between initial ADD clinical diagnosis and death is approximately 8 years (129), but AβPs and NFTs are present well over a decade before death (130-138).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [132]
Hippocampal atrophy is detectable prior to the diagnosis of Alzheimer's disease, at the stage of amnestic Mild Cognitive Impairment or earlier in asymptomatic elderly.
“Using MRI, this atrophy is detectable prior to the diagnosis of AD, at the stage of amnestic Mild Cognitive Impairment (aMCI) (Convit et al., 1997; Shi et al., 2009) or even earlier, in asymptomatic elderly up to 10 years before the diagnosis of dementia (Smith et al., 2007; Tondelli et al., 2012).”
From Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia (2013) · cites this paper as Smith et al., 2007
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- Authors
- Smith, C. D., Chebrolu, H., Wekstein, D. R., Schmitt, F. A., Jicha, G. A., Cooper, G., & Markesbery, W. R.
- Affiliations
- From the Departments of Neurology (C.D.S., H.C., F.A.S., G.A.J., W.R.M.), Anatomy and Neurobiology (C.D.S., W.R.M.), Pathology (W.R.M.), Behavioral Science (F.A.S.), Psychiatry (F.A.S.), and Psychology (F.A.S.), Magnetic Resonance Imaging and Spectroscopy Center (C.D.S., H.C.), and Alzheimer's Disease Center and Sanders-Brown Center on Aging (C.D.S., D.R.W., F.A.S., G.A.J., G.C., W.R.M.), University of Kentucky College of Medicine, Lexington.
- Venue
- Neurology
- Published
- 2007-04-17
- Volume
- 68
- Issue
- 16
- Pages
- 1268-1273
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2020623898
- Cited by
- 161
- References
- 49
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 2 · 2016: 7 · 2015: 7 · 2014: 7 · 2013: 13 · 2012: 14
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Kentucky
- National Institute on Aging (P30AG028383)
- National Institute of Neurological Disorders and Stroke (5R01 NS-36660, R01NS036660)
- National Center for Research Resources (5M01RR02602, M01RR002602)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- mild cognitive impairment, Alzheimer's disease, brain structural changes, gray matter loss, angular gyrus, hippocampus, amygdala, entorhinal cortex, normal aging, prodromal Alzheimer's disease, voxel-based morphometry
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Cognition, Cognition Disorders, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Neural Pathways, Parietal Lobe, Predictive Value of Tests, Temporal Lobe, Disease Progression
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