O4‐03‐03: Risk factors for amyloid deposition in healthy aging: Effects of hypertension and genetic risk

Rodrigue, Karen M.; Rieck, Jenny; Kennedy, Kristen M.; Devous, Michael D.; Park, Denise

doi:10.1016/j.jalz.2012.05.1648

Cited by 20 publications

(35 citation statements)

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“…Because previous in vivo reports have not accounted for Ab, it was not known whether Ab drove these effects, especially since vascular risk has been found to be associated with higher cerebral Ab in older adults without dementia. 3,4,6 One notable finding of this study is therefore the significant effect of high aggregate vascular risk and low HDL cholesterol on cortical thickness that is not explained by the presence of fibrillar Ab ( figure 1, E and H). This effect was mainly seen in the anterior parts of temporal cortex and the superior frontal gyrus.…”

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confidence: 60%

“…1,2 In vivo studies show that increased vascular risk is related to higher Ab burden. [3][4][5][6] Other work suggests that VBI per se is not associated with elevated Ab, and that the effects of VBI and Ab on brain structure and cognition are independent. 7,8 Together, these findings suggest that vascular risk factors may have independent effects on Ab and VBI, and therefore increase AD risk through multiple pathways.…”

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confidence: 99%

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Vascular risk and Aβ interact to reduce cortical thickness in AD vulnerable brain regions

et al. 2014

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Objective: The objective of this study was to define whether vascular risk factors interact with b-amyloid (Ab) in producing changes in brain structure that could underlie the increased risk of Alzheimer disease (AD).Methods: Sixty-six cognitively normal and mildly impaired older individuals with a wide range of vascular risk factors were included in this study. The presence of Ab was assessed using [11 C] Pittsburgh compound B-PET imaging, and cortical thickness was measured using 3-tesla MRI. Vascular risk was measured with the Framingham Coronary Risk Profile Index.Results: Individuals with high levels of vascular risk factors have thinner frontotemporal cortex independent of Ab. These frontotemporal regions are also affected in individuals with Ab deposition, but the latter show additional thinning in parietal cortices. Ab and vascular risk were found to interact in posterior (especially in parietal) brain regions, where Ab has its greatest effect. In this way, the negative effect of Ab in posterior regions is increased by the presence of vascular risk. The prevalence of b-amyloid (Ab), the hallmark of Alzheimer disease (AD), is approximately 25% among cognitively normal elderly individuals, indicating that Ab alone might not be sufficient to drive brain changes and cognitive decline, and that other factors work with Ab to promote disease onset or progression. Vascular risk factors such as hypertension, dyslipidemia, and diabetes are known risk factors for dementia in persons with clinical syndromes suggesting AD pathology. Conclusion:1 One pathway by which vascular risk increases the likelihood of dementia is by causing vascular brain injury (VBI) (e.g., white matter lesions and infarcts). 1,2In vivo studies show that increased vascular risk is related to higher Ab burden. [3][4][5][6] Other work suggests that VBI per se is not associated with elevated Ab, and that the effects of VBI and Ab on brain structure and cognition are independent. 7,8 Together, these findings suggest that vascular risk factors may have independent effects on Ab and VBI, and therefore increase AD risk through multiple pathways.Integrity of the cerebral cortex is a major determinant of cognitive function. 9 A better understanding of the interplay between vascular risk and Ab pathology in relation to cortical thickness might yield insight into the factors that drive the development of AD. In this study, we assessed how Ab and vascular risk, alone and together, affect cerebral cortex, specifically evaluating

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confidence: 60%

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confidence: 99%

Vascular risk and Aβ interact to reduce cortical thickness in AD vulnerable brain regions

et al. 2014

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“…In addition, APOE e4 allele exacerbates cognitive decline associated with vascular risk factors, possibly by affecting the extent to which vascular factors influence white matter integrity. [7][8][9] However, no previous research has examined the interactive effect of APOE e4 and vascular factors on white matter microstructure.…”

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confidence: 99%

Effects of vascular risk factors and APOE ε4 on white matter integrity and cognitive decline

et al. 2015

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Objective: To investigate the effects of vascular risk factors and APOE status on white matter microstructure, and subsequent cognitive decline among older people.Methods: This study included 241 participants (age 60 years and older) from the populationbased Swedish National Study on Aging and Care in Kungsholmen in central Stockholm, Sweden, who were free of dementia and stroke at baseline (2001)(2002)(2003)(2004). We collected data through interviews, clinical examinations, and laboratory tests. We measured fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging, and estimated volume of white matter hyperintensities using automatic segmentation. We assessed global cognitive function with the Mini-Mental State Examination at baseline and at 3-and/or 6-year follow-up. We analyzed the data using multivariate linear regression and linear mixed models.Results: Heavy alcohol consumption, hypertension, and diabetes were significantly associated with lower FA or higher MD (p , 0.05). When aggregating heavy alcohol consumption, hypertension, and diabetes together with current smoking, having an increasing number of these 4 factors concurrently was associated with decreasing FA and increasing MD (p trend , 0.01), independent of white matter hyperintensities. Vascular risk factors and APOE e4 allele interacted to negatively affect white matter microstructure; having multiple ($2) vascular factors was particularly detrimental to white matter integrity among APOE e4 carriers. Lower tertile of FA and upper tertile of MD were significantly associated with faster Mini-Mental State Examination decline.Conclusions: Vascular risk factors are associated with reduced white matter integrity among older adults, which subsequently predicted faster cognitive decline. The detrimental effects of vascular risk factors on white matter microstructure were exacerbated among APOE e4 carriers. Neurology ® 2015;84:1128-1135 GLOSSARY DTI 5 diffusion tensor imaging; FA 5 fractional anisotropy; MD 5 mean diffusivity; MMSE 5 Mini-Mental State Examination; SNAC-K 5 Swedish National Study on Aging and Care in Kungsholmen; WMH 5 white matter hyperintensity.Population-based studies have linked some individual vascular risk factors (e.g., hypertension and diabetes) to reduced microstructural white matter integrity.1-3 However, few studies have explored the relationship of clustering vascular risk factors to white matter microstructure. This is important because vascular factors often occur concurrently in older people. Moreover, as white matter hyperintensities (WMH) and reduced white matter microstructure may share a common ischemic origin, it is of interest to explore whether associations between vascular risk factors and lower microstructural white matter integrity are independent of WMH.Vascular risk factors contribute to cognitive decline in aging, but the mechanisms are poorly understood. 4 One possibility is that vascular risk factors may cause cognitive decline by conferring detrimental impact on white matter mi...

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“…45 These findings provide evidence that treatment of CVRFs may change the impact of APOE on amyloid deposition. The more widespread use of amyloid imaging is expected to foster longitudinal studies that use this technology to measure the effect of interventions.…”

Section: Unraveling the Relationship Between Ad And Cardiovascular Rimentioning

confidence: 73%

“…43 Moreover, amyloid-b deposition --a pathological hallmark of AD which can now be measured in vivo with amyloid imaging techniques --has been associated with vascular risk factors such as physical inactivity, higher plasma concentrations of cortisol, and hypertension. [44][45][46] The diagnosis of MCI has also been associated with several CVRFs; these include hypertension, 47,48 diabetes, 49,50 and increased cholesterol levels. 51,52 A recent large neuropathological study (5,715 cases) found that vascular pathology is more prevalent in patients with AD than in those with frontotemporal lobar degeneration, dementia with Lewy bodies, or Parkinson's disease dementia.…”

Section: Cardiovascular Risk Factors and Cognitive Declinementioning

confidence: 99%

The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

Ferreira

Tamashiro-Duran

Squarzoni

et al. 2014

Rev. Bras. Psiquiatr.

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Objective: To review functional neuroimaging studies about the relationship between cardiovascular risk factors (CVRFs), Alzheimer's disease (AD), and mild cognitive impairment (MCI). Methods: We performed a comprehensive literature search to identify articles in the neuroimaging field addressing CVRF in AD and MCI. We included studies that used positron emission tomography (PET), single photon emission computerized tomography (SPECT), or functional magnetic resonance imaging (fMRI). Results: CVRFs have been considered risk factors for cognitive decline, MCI, and AD. Patterns of AD-like changes in brain function have been found in association with several CVRFs (both regarding individual risk factors and also composite CVRF measures). In vivo assessment of AD-related pathology with amyloid imaging techniques provided further evidence linking CVRFs and AD, but there is still limited information resulting from this new technology. Conclusion: There is a large body of evidence from functional neuroimaging studies supporting the hypothesis that CVRFs may play a causal role in the pathophysiology of AD. A major limitation of most studies is their cross-sectional design; future longitudinal studies using multiple imaging modalities are expected to better document changes in CVRF-related brain function patterns and provide a clearer picture of the complex relationship between aging, CVRFs, and AD.

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O4‐03‐03: Risk factors for amyloid deposition in healthy aging: Effects of hypertension and genetic risk

Cited by 20 publications

References 0 publications

Vascular risk and Aβ interact to reduce cortical thickness in AD vulnerable brain regions

Vascular risk and Aβ interact to reduce cortical thickness in AD vulnerable brain regions

Effects of vascular risk factors and APOE ε4 on white matter integrity and cognitive decline

The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

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