Stroke risk interacts with Alzheimer's disease biomarkers on brain aging outcomes

Abstract

Alzheimer's disease (AD) biomarkers and stroke risk factors independently predict cognitive impairment, likely through independent disease pathways. However, limited work has sought to describe the dynamic interplay between these important risk factors. This manuscript evaluated the interaction between stroke risk and AD biomarkers on hippocampal volume and cognitive performance. We first evaluated the interaction between stroke risk factors and AD biomarkers using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, n=1202). We then extended our findings to an independent autopsy dataset from the National Alzheimer's Coordinating Center (NACC, n=1122) using measures of AD pathology. Stroke risk was quantified using the Framingham Stroke Risk Profile. In ADNI, stroke risk interacted with tau and amyloid levels in relation to baseline and longitudinal cognitive performance. Similarly, in NACC, stroke risk interacted with amyloid and tau positivity on cognitive performance. The effect of stroke risk factors on cognition was strongest in the absence of AD biomarkers or neuropathology, providing additional evidence that AD biomarkers and stroke risk factors relate to cognition through independent pathways.

Insulin-like growth factor binding protein-2 interactions with Alzheimer’s disease biomarkers

“…In previous work leveraging both ADNI data and autopsy data from the National Alzheimer's Coordinating Center (NACC), we observed a comparable interaction between the Framingham Stroke Risk Profile and CSF biomarkers of AD neuropathology whereby the effect of vascular risk on hippocampal volume and cognition was strongest among individuals who were AD biomarker negative (Hohman et al, 2015). The results of both the current and previous work support the possibility that vascular and insulin interventions for cognitive impairment may be most beneficial among individuals who are AD biomarker negative.…”

“…Second, we assess the interaction between CSF biomarkers of AD neuropathology and IGFBP-2 on these same AD-relevant outcomes. We hypothesize that, similar to effect of vascular risk factors (Hohman et al, 2015), IGFBP-2 acts through a non-AD pathway and thus will show the strongest association with hippocampal volume, episodic memory performance, and executive function performance among biomarker negative individuals.…”

Life and death in the trash heap: The ubiquitin proteasome pathway and UCHL1 in brain aging, neurodegenerative disease and cerebral Ischemia

“…Obstructive sleep apnea and diabetes are common in the elderly and are associated with transient hypoxia and hypopglycemia that may also contribute to brain injury and insults to the UPP (Balfors and Franklin, 1994; Gozal, 2013; Gozal et al, 2003; Iadecola, 2003). Thus, the epidemiological association between vascular risk factors, stroke and AD may be due to the effects of chronic ischemia on the UPP resulting in impaired clearance of abnormal proteins (Gupta and Iadecola, 2015; Hohman et al, 2015; Jefferson et al, 2015; Kapasi and Schneider, 2016). …”

APP as a Protective Factor in Acute Neuronal Insults

“…Other studies, however, did not find an increased risk of ischemic stroke in patients with AD (Imfeld et al, 2013 ; Tolppanen et al, 2013 ; Zhou et al, 2015 ). Not surprisingly, cerebrovascular disease and AD contribute additively to cognitive impairment in patients (Hohman et al, 2015 ) and mouse models (Pimentel-Coelho et al, 2013 ), possibly forming a vicious cycle of ischemia and neurodegeneration (Pluta et al, 2013 ).…”