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Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly.

Scott JA, Braskie MN, Tosun D, Thompson PM, Weiner M, DeCarli C, Carmichael OT, Alzheimer’s Disease Neuroimaging Initiati - Front Aging Neurosci (2015)

Bottom Line: In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD).SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes.Clinical histories of VRFs, as well as current measurements of vascular status, were recorded during a baseline clinical evaluation.

View Article: PubMed Central - PubMed

Affiliation: IDeA Laboratory, Department of Neurology, University of California, Davis Davis, CA, USA.

ABSTRACT
In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD). SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes. However, cerebral amyloid accumulation is also prevalent in this population and is associated with WMH accrual. Therefore, we examined the independent associations of amyloid burden and VRFs with WMH burden in CN elderly individuals with low to moderate vascular risk. Participants (n = 150) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) received fluid attenuated inversion recovery (FLAIR) MRI at study entry. Total WMH volume was calculated from FLAIR images co-registered with structural MRI. Amyloid burden was determined by cerebrospinal fluid Aβ1-42 levels. Clinical histories of VRFs, as well as current measurements of vascular status, were recorded during a baseline clinical evaluation. We tested ridge regression models for independent associations and interactions of elevated blood pressure (BP) and amyloid to total WMH volume. We found that greater amyloid burden and a clinical history of hypertension were independently associated with greater WMH volume. In addition, elevated BP modified the association between amyloid and WMH, such that those with either current or past evidence of elevated BP had greater WMH volumes at a given burden of amyloid. These findings are consistent with the hypothesis that cerebral amyloid accumulation and VRFs are independently associated with clinically latent white matter damage represented by WMHs. The potential contribution of amyloid to WMHs should be further explored, even among elderly individuals without cognitive impairment and with limited VRF exposure.

No MeSH data available.


Related in: MedlinePlus

Using parameter estimates from Table 3, estimated trends of WMH volume as a function of age, is shown for prototype individuals with mean ICV and normal BP/negative amyloid (blue, dashed), normal BP/positive amyloid (blue, solid), high BP/negative amyloid (red, dashed), and high BP/positive amyloid (red, solid). Amyloid positive threshold was CSF Aβ1-42 ≤ 192 pg/ml; the amyloid level used in these calculations is the mean for each category.
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Figure 2: Using parameter estimates from Table 3, estimated trends of WMH volume as a function of age, is shown for prototype individuals with mean ICV and normal BP/negative amyloid (blue, dashed), normal BP/positive amyloid (blue, solid), high BP/negative amyloid (red, dashed), and high BP/positive amyloid (red, solid). Amyloid positive threshold was CSF Aβ1-42 ≤ 192 pg/ml; the amyloid level used in these calculations is the mean for each category.

Mentions: Figure 2 gives an illustrative example of model-predicted WMH volumes for the population average ICV by age, exposure to elevated BP, and CSF Aβ1-42 burden. As expected, WMH volume is predicted to increase with age, and at each age WMH volume is predicted to be greater in those exposed to elevated BP. However, in individuals with high CSF Aβ1-42 burden and no evidence of elevated BP exposure, WMH burden is predicted to be about as high as in those exposed to elevated BP. Finally, the highest WMH burdens are predicted for those individuals who were both exposed to elevated BP and carry high CSF Aβ1-42 burden (Table 4).


Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly.

Scott JA, Braskie MN, Tosun D, Thompson PM, Weiner M, DeCarli C, Carmichael OT, Alzheimer’s Disease Neuroimaging Initiati - Front Aging Neurosci (2015)

Using parameter estimates from Table 3, estimated trends of WMH volume as a function of age, is shown for prototype individuals with mean ICV and normal BP/negative amyloid (blue, dashed), normal BP/positive amyloid (blue, solid), high BP/negative amyloid (red, dashed), and high BP/positive amyloid (red, solid). Amyloid positive threshold was CSF Aβ1-42 ≤ 192 pg/ml; the amyloid level used in these calculations is the mean for each category.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664630&req=5

Figure 2: Using parameter estimates from Table 3, estimated trends of WMH volume as a function of age, is shown for prototype individuals with mean ICV and normal BP/negative amyloid (blue, dashed), normal BP/positive amyloid (blue, solid), high BP/negative amyloid (red, dashed), and high BP/positive amyloid (red, solid). Amyloid positive threshold was CSF Aβ1-42 ≤ 192 pg/ml; the amyloid level used in these calculations is the mean for each category.
Mentions: Figure 2 gives an illustrative example of model-predicted WMH volumes for the population average ICV by age, exposure to elevated BP, and CSF Aβ1-42 burden. As expected, WMH volume is predicted to increase with age, and at each age WMH volume is predicted to be greater in those exposed to elevated BP. However, in individuals with high CSF Aβ1-42 burden and no evidence of elevated BP exposure, WMH burden is predicted to be about as high as in those exposed to elevated BP. Finally, the highest WMH burdens are predicted for those individuals who were both exposed to elevated BP and carry high CSF Aβ1-42 burden (Table 4).

Bottom Line: In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD).SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes.Clinical histories of VRFs, as well as current measurements of vascular status, were recorded during a baseline clinical evaluation.

View Article: PubMed Central - PubMed

Affiliation: IDeA Laboratory, Department of Neurology, University of California, Davis Davis, CA, USA.

ABSTRACT
In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD). SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes. However, cerebral amyloid accumulation is also prevalent in this population and is associated with WMH accrual. Therefore, we examined the independent associations of amyloid burden and VRFs with WMH burden in CN elderly individuals with low to moderate vascular risk. Participants (n = 150) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) received fluid attenuated inversion recovery (FLAIR) MRI at study entry. Total WMH volume was calculated from FLAIR images co-registered with structural MRI. Amyloid burden was determined by cerebrospinal fluid Aβ1-42 levels. Clinical histories of VRFs, as well as current measurements of vascular status, were recorded during a baseline clinical evaluation. We tested ridge regression models for independent associations and interactions of elevated blood pressure (BP) and amyloid to total WMH volume. We found that greater amyloid burden and a clinical history of hypertension were independently associated with greater WMH volume. In addition, elevated BP modified the association between amyloid and WMH, such that those with either current or past evidence of elevated BP had greater WMH volumes at a given burden of amyloid. These findings are consistent with the hypothesis that cerebral amyloid accumulation and VRFs are independently associated with clinically latent white matter damage represented by WMHs. The potential contribution of amyloid to WMHs should be further explored, even among elderly individuals without cognitive impairment and with limited VRF exposure.

No MeSH data available.


Related in: MedlinePlus