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Updated: Jun 18, 2026
Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Differences in brain volume, hippocampal volume, cerebrovascular risk factors, and apolipoprotein E4 among mild
Jing He1, Sarah Farias, Oliver Martinez
1Department of Neurology, and the Imaging of Dementia and Aging Laboratory, Center for Neuroscience Preventive Medicine, University of California at Davis, Sacramento, CA 95817, USA.
Objectives:
To evaluate demographics, magnetic resonance imaging (MRI) measures, and vascular risk among mild cognitive impairment (MCI) subtypes.
Design:
Cross-sectional study.
Setting:
Both clinics and the community.
Participants:
A total of 153 subjects with MCI, 218 cognitively normal older individuals (controls), and 68 patients with Alzheimer disease.
Main Outcome Measures:
Classification of subjects with MCI according to current subtype diagnostic convention based on neuropsychological performance, estimates of vascular risk based on medical history, research MRI unless there was a specific contraindication, and apolipoprotein E genotype.
Results:
Of the 153 subjects with MCI, 65 were diagnosed with amnestic single-domain, 46 with amnestic multiple-domain, 27 with nonamnestic single-domain, and 15 with nonamnestic multiple-domain MCI. Analyses of control, MCI, and Alzheimer disease cases revealed significant differences in brain and hippocampal volumes between each group. Post hoc analyses of MRI measures among the MCI subtypes found that patients with amnestic single-domain MCI had significantly less brain atrophy and that hippocampal volume differed significantly from controls for the 2 amnestic forms of MCI. Apolipoprotein E genotype prevalence was significantly greater in the amnestic and nonamnestic subtypes of MCI. Conversely, the nonamnestic subtypes were more likely to have increased vascular risk and to be African American.
Conclusions:
Amnestic forms of MCI appear to have demographic, genetic, and MRI findings suggestive of Alzheimer disease pathology, whereas the nonamnestic forms of MCI have findings suggestive of vascular disease. Importantly, however, all subjects with MCI showed evidence of brain injury, and the biological differences among subtypes are relatively subtle beyond the memory vs nonmemory groupings.
Insights
Mild cognitive impairment (MCI) subtypes show distinct patterns. Amnestic MCI may indicate Alzheimer's pathology, while nonamnestic MCI suggests vascular issues, though all MCI types exhibit brain injury.
Area of Science:
- Neurology
- Neuroimaging
- Geriatrics
Background:
- Mild cognitive impairment (MCI) is a transitional stage between normal aging and dementia.
- Understanding MCI subtypes is crucial for accurate diagnosis and targeted interventions.
- Existing research suggests heterogeneity within MCI, necessitating further investigation into its subtypes.
Purpose of the Study:
- To investigate demographic, neuroimaging (MRI), and vascular risk differences across mild cognitive impairment (MCI) subtypes.
- To compare these factors between MCI subtypes, cognitively normal controls, and Alzheimer disease patients.
Main Methods:
- Cross-sectional study involving 153 MCI subjects, 218 controls, and 68 Alzheimer disease patients.
- MCI subtypes classified based on neuropsychological performance.
- Vascular risk assessed via medical history; MRI used for brain and hippocampal volumes; apolipoprotein E genotyping performed.
Main Results:
- Significant differences in brain and hippocampal volumes were observed across control, MCI, and Alzheimer disease groups.
- Amnestic MCI subtypes showed less brain atrophy and altered hippocampal volumes compared to controls.
- Apolipoprotein E genotype was more prevalent in amnestic and nonamnestic MCI; nonamnestic subtypes had higher vascular risk and African American prevalence.
Conclusions:
- Amnestic MCI subtypes exhibit characteristics aligning with Alzheimer disease pathology.
- Nonamnestic MCI subtypes present findings suggestive of underlying vascular disease.
- All MCI subtypes demonstrate evidence of brain injury, with subtle biological distinctions beyond memory versus non-memory impairments.
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