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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

Lesser CSF Aβ1-42 was associated with greater white matter hyperintensities (WMH) volume across all participants, adjusting for age and intracranial volume (Table 2). This association was driven by the high blood pressure (BP) group (red, β = –0.356, p < 0.001). CSF Aβ1-42 was not significantly associated with WMH volume in the Normal BP group (blue, β = – 0.102, p = 0.429).
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Figure 1: Lesser CSF Aβ1-42 was associated with greater white matter hyperintensities (WMH) volume across all participants, adjusting for age and intracranial volume (Table 2). This association was driven by the high blood pressure (BP) group (red, β = –0.356, p < 0.001). CSF Aβ1-42 was not significantly associated with WMH volume in the Normal BP group (blue, β = – 0.102, p = 0.429).

Mentions: In the second model, greater age, greater ICV, lesser CSF Aβ1-42, high BP exposure, and CSF Aβ1-42 by BP exposure group were significantly associated with greater WMH volume (Table 3). The BP exposure group significantly modified the association between CSF Aβ1-42 and WMH volume (Table 3; Figure 1). Specifically, among those who showed evidence of exposure to elevated BP, a low CSF Aβ1-42 (i.e., higher cerebral Aβ1-42) was associated with a greater WMH volume than in the normal BP group. Quantitatively, in the elevated BP group, each standard deviation decrease in CSF Aβ1-42 was associated with an 0.18-fold standard deviation increase in WMH; meanwhile in the normal BP group, each standard deviation decrease in CSF Aβ1-42 was only associated with an 0.01-fold standard deviation increase in WMH.


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)

Lesser CSF Aβ1-42 was associated with greater white matter hyperintensities (WMH) volume across all participants, adjusting for age and intracranial volume (Table 2). This association was driven by the high blood pressure (BP) group (red, β = –0.356, p < 0.001). CSF Aβ1-42 was not significantly associated with WMH volume in the Normal BP group (blue, β = – 0.102, p = 0.429).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Lesser CSF Aβ1-42 was associated with greater white matter hyperintensities (WMH) volume across all participants, adjusting for age and intracranial volume (Table 2). This association was driven by the high blood pressure (BP) group (red, β = –0.356, p < 0.001). CSF Aβ1-42 was not significantly associated with WMH volume in the Normal BP group (blue, β = – 0.102, p = 0.429).
Mentions: In the second model, greater age, greater ICV, lesser CSF Aβ1-42, high BP exposure, and CSF Aβ1-42 by BP exposure group were significantly associated with greater WMH volume (Table 3). The BP exposure group significantly modified the association between CSF Aβ1-42 and WMH volume (Table 3; Figure 1). Specifically, among those who showed evidence of exposure to elevated BP, a low CSF Aβ1-42 (i.e., higher cerebral Aβ1-42) was associated with a greater WMH volume than in the normal BP group. Quantitatively, in the elevated BP group, each standard deviation decrease in CSF Aβ1-42 was associated with an 0.18-fold standard deviation increase in WMH; meanwhile in the normal BP group, each standard deviation decrease in CSF Aβ1-42 was only associated with an 0.01-fold standard deviation increase in WMH.

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