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

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.

Cerebral amyloid is associated with greater white-matter hyperintensity accrual in cognitively normal older adults

“…We and others previously demonstrated that in CN, elevated cerebral amyloid is associated with greater WMH burden and broadly reduced WM integrity, measured by DTI (Gold et al, 2014; Marnane et al, 2016; Scott et al, 2015; Wolf et al, 2015). However, these cross-sectional studies fell short of providing information about temporal relationships between amyloid burden and WMH accrual, and in particular, whether the presence of cerebral amyloid is associated with greater subsequent accrual of WMH—as would be predicted by current data on the neurobiological consequences of amyloid (Brickman, 2013; Saito and Ihara, 2016).…”

“…The current state of care associated with WMH is to manage vascular risk factors to reduce growth of white-matter lesions (Mok and Kim, 2015). However, even when vascular risk is low or vascular factors, such as hypertension, are treated, WMH load remains elevated (Scott et al, 2015). This prompts the investigation of additional factors, like cerebral amyloid, that could be modulated to lessen the accumulation of aging-associated white-matter damage.…”

Cerebral Hypoperfusion and the Energy Deficit in Alzheimer's Disease

“…Other evidence for a relationship between amyloid burden and WMH comes from an MRI study of 150 cognitively normal people by Scott et al (122). The authors found that amyloid burden, as assessed by measuring Aβ42 level in the CSF, was an independent predictor of total WMH volume.…”

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer’s Disease

“…Such differences are regionally specific in that the most consistent and notable age-related differences are noted in the prefrontal and medial temporal regions (Buckner 2004;DeCarli 2013;DeCarli et al 1995;Fjell et al 2013Fjell et al , 2014Head et al 2008;Raz et al 2005). Indeed, age-related differences are found in white matter microstructure which may underpin gray matter atrophy differences (AndrewsHanna et al 2007; O' Sullivan et al 2001;Sullivan et al 2001;Pfefferbaum 2006, 2007;Scott et al 2015). Thus, age-related dysfunction in specific brain regions/systems may be a manifestation of an inherent dysfunctional relationship between different cardinal pathological factors (involving white and gray matters) (DeCarli 2013; Scott et al 2015).…”

“…Indeed, age-related differences are found in white matter microstructure which may underpin gray matter atrophy differences (AndrewsHanna et al 2007; O' Sullivan et al 2001;Sullivan et al 2001;Pfefferbaum 2006, 2007;Scott et al 2015). Thus, age-related dysfunction in specific brain regions/systems may be a manifestation of an inherent dysfunctional relationship between different cardinal pathological factors (involving white and gray matters) (DeCarli 2013; Scott et al 2015). Advanced age upregulates multiple overlapping pathobiological processes; these have an adverse effect on brain structure and function (Daulatzai 2012a(Daulatzai , 2013a(Daulatzai , 2014(Daulatzai , 2016d.…”