期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 72, 期 1, 页码 215-228出版社
IOS PRESS
DOI: 10.3233/JAD-190691
关键词
Alzheimer's disease; amyloid; APOE; C-11-PIB; cerebrovascular lesions; cognition; follow-up study; insulin resistance; magnetic resonance imaging; PET scan
资金
- Finnish Governmental Research Funding (ERVA)
- Pro Humanitate Foundation
- Finnish Cultural Foundation
- Sigrid Juselius Foundation
- Academy of Finland [310962]
- Betania Foundation
- Uulo Arhio Foundation
- Orion Research Foundation
- Paulo Foundation
- Finnish Medical Foundation
- Academy of Finland (AKA) [310962, 310962] Funding Source: Academy of Finland (AKA)
Background: Type 2 diabetes (T2DM) increases the risk for Alzheimer's disease (AD) but not for AD neuropathology. The association between T2DM and AD is assumed to be mediated through vascular mechanisms. However, insulin resistance (IR), the hallmark of T2DM, has been shown to associate with AD neuropathology and cognitive decline. Objective: To evaluate if midlife IR predicts late-life cognitive performance and cerebrovascular lesions (white matter hyperintensities and total vascular burden), and whether cerebrovascular lesions and brain amyloid load are associated with cognitive functioning. Methods: This exposure-to-control follow-up study examined 60 volunteers without dementia (mean age 70.9 years) with neurocognitive testing, brain 3T-MRI and amyloid-PET imaging. The volunteers were recruited from the Finnish Health 2000 survey (n = 6062) to attend follow-up examinations in 2014-2016 according to their insulin sensitivity in 2000 and their APOE genotype. The exposure group (n = 30) had IR in 2000 and the 30 controls had normal insulin sensitivity. There were 15 APOE epsilon 4 carriers per group. Statistical analyses were performed with multivariable linear models. Results: At follow-up the IR+group performed worse on executive functions (p = 0.02) and processing speed (p = 0.007) than the IR- group. The groups did not differ in cerebrovascular lesions. No associations were found between cerebrovascular lesions and neurocognitive test scores. Brain amyloid deposition associated with slower processing speed. Conclusion: Midlife IR predicted poorer executive functions and slower processing speed, but not cerebrovascular lesions. Brain amyloid deposition was associated with slower processing speed. The association between midlife IR and late-life cognition might not be mediated through cerebrovascular lesions measured here.
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