Association between lifetime coffee consumption and late life cerebral white matter hyperintensities in cognitively normal elderly individuals

White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH ( P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD ( P<0.005). Lower gain was associated with higher FA in the LF range ( P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals.

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Arterial stiffness and progression of cerebral white matter hyperintensities in patients with type 2 diabetes and matched controls: a 5-year cohort study

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00691-y ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Kristian L. Funck ◽

Esben Laugesen ◽

Pernille Høyem ◽

Brian Stausbøl-Grøn ◽

Won Y. Kim ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cohort Study ◽

White Matter ◽

Arterial Stiffness ◽

White Matter Hyperintensities ◽

Cerebrovascular Diseases ◽

Study Data ◽

Cerebral White Matter ◽

Intracranial Volume

Abstract Background Stroke is a serious complication in patients with type 2 diabetes (T2DM). Arterial stiffness may improve stroke prediction. We investigated the association between carotid-femoral pulse wave velocity [PWV] and the progression of cerebral white matter hyperintensities (WMH), a marker of stroke risk, in patients with T2DM and controls. Methods In a 5-year cohort study, data from 45 patients and 59 non-diabetic controls were available for analysis. At baseline, participants had a mean (± SD) age of 59 ± 10 years and patients had a median (range) diabetes duration of 1.8 (0.8–3.2) years. PWV was obtained by tonometry and WMH volume by an automated segmentation algorithm based on cerebral T2-FLAIR and T1 MRI (corrected by intracranial volume, cWMH). High PWV was defined above 8.94 m/s (corresponding to the reference of high PWV above 10 m/s using the standardized path length method). Results Patients with T2DM had a higher PWV than controls (8.8 ± 2.2 vs. 7.9 ± 1.4 m/s, p < 0.01). WMH progression were similar in the two groups (p = 0.5). One m/s increase in baseline PWV was associated with a 16% [95% CI 1–32%], p < 0.05) increase in cWMH volume at 5 years follow-up after adjustment for age, sex, diabetes, pulse pressure and smoking. High PWV was associated with cWMH progression in the combined cohort (p < 0.05). We found no interaction between diabetes and PWV on cWMH progression. Conclusions PWV is associated with cWMH progression in patients with type 2 diabetes and non-diabetic controls. Our results indicate that arterial stiffness may be involved early in the pathophysiology leading to cerebrovascular diseases.

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Vascular lesions and functional limitations among older adults: does depression make a difference?

International Psychogeriatrics ◽

10.1017/s1041610214000829 ◽

2014 ◽

Vol 26 (9) ◽

pp. 1501-1509 ◽

Cited By ~ 5

Author(s):

Celia F. Hybels ◽

Carl F. Pieper ◽

Lawrence R. Landerman ◽

Martha E. Payne ◽

David C. Steffens

Keyword(s):

Risk Factors ◽

Older Adults ◽

White Matter ◽

Functional Impairment ◽

Functional Limitations ◽

Late Life ◽

Cognitive Status ◽

Cerebral White Matter ◽

Late Life Depression ◽

Increased Risk

ABSTRACTBackground:The association between disability and depression is complex, with disability well established as a correlate and consequence of late life depression. Studies in community samples report that greater volumes of cerebral white matter hyperintensities (WMHs) seen on brain imaging are linked with functional impairment. These vascular changes are also associated with late life depression, but it is not known if depression is a modifier in the relationship between cerebrovascular changes and functional impairment.Methods:The study sample was 237 older adults diagnosed with major depression and 140 never depressed comparison adults, with both groups assessed at study enrollment. The dependent variable was the number of limitations in basic activities of daily living (ADL), instrumental ADLs, and mobility tasks. The independent variable was the total volume of cerebral white matter lesions or hyperintensities assessed though magnetic resonance imaging.Results:In analyses controlling for age, sex, race, high blood pressure, and cognitive status, a greater volume of WMH was positively associated with the total number of functional limitations as well as the number of mobility limitations among those older adults with late life depression but not among those never depressed, suggesting the association between WMH volume and functional status differs in the presence of late life depression.Conclusions:These findings suggest older patients with both depression and vascular risk factors may be at an increased risk for functional decline, and may benefit from management of both cerebrovascular risk factors and depression.

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Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

Journal of Alzheimer s Disease ◽

10.3233/jad-210333 ◽

2021 ◽

pp. 1-11

Author(s):

Fennie Choy Chin Wong ◽

Seyed Ehsan Saffari ◽

Chathuri Yatawara ◽

Kok Pin Ng ◽

Nagaendran Kandiah ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Executive Function ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Amyloid Β ◽

Intracranial Volume ◽

Linear Regression Models ◽

Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

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