Association of Vascular Risk Factors With β-Amyloid Peptide and Tau Burdens in Cognitively Unimpaired Individuals and Its Interaction With Vascular Medication Use

Köbe, Theresa; Gonneaud, Julie; Binette, Alexa Pichet; Meyer, Pierre‐François; McSweeney, Melissa; Rosa‐Neto, Pedro; Breitner, John C.S.; Poirier, Judes; Villeneuve, Sylvia

doi:10.1001/jamanetworkopen.2019.20780

Cited by 39 publications

(38 citation statements)

References 57 publications

(98 reference statements)

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“…Additionally, Bowman and colleagues investigated the relationship between the BBB and the pathology of AD and found that dyslipidemia was prevalent in 47% of study participants with mild-to-moderate AD and 75% of those who had AD with BBB impairment, suggesting that dyslipidemia may play a role in decreasing BBB integrity [ 269 ]. Total cholesterol and low-density lipoprotein cholesterol levels have also been associated with increased Aβ burden in humans [ 224, 270 ].…”

Section: Promoting Successful Cognitive Agingmentioning

confidence: 99%

Promoting Successful Cognitive Aging: A Ten-Year Update

Krivanek

Gale

McFeeley

et al. 2021

JAD

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A decade has passed since we published a comprehensive review in this journal addressing the topic of promoting successful cognitive aging, making this a good time to take stock of the field. Because there have been limited large-scale, randomized controlled trials, especially following individuals from middle age to late life, some experts have questioned whether recommendations can be legitimately offered about reducing the risk of cognitive decline and dementia. Despite uncertainties, clinicians often need to at least make provisional recommendations to patients based on the highest quality data available. Converging lines of evidence from epidemiological/cohort studies, animal/basic science studies, human proof-of-concept studies, and human intervention studies can provide guidance, highlighting strategies for enhancing cognitive reserve and preventing loss of cognitive capacity. Many of the suggestions made in 2010 have been supported by additional research. Importantly, there is a growing consensus among major health organizations about recommendations to mitigate cognitive decline and promote healthy cognitive aging. Regular physical activity and treatment of cardiovascular risk factors have been supported by all of these organizations. Most organizations have also embraced cognitively stimulating activities, a heart-healthy diet, smoking cessation, and countering metabolic syndrome. Other behaviors like regular social engagement, limiting alcohol use, stress management, getting adequate sleep, avoiding anticholinergic medications, addressing sensory deficits, and protecting the brain against physical and toxic damage also have been endorsed, although less consistently. In this update, we review the evidence for each of these recommendations and offer practical advice about behavior-change techniques to help patients adopt brain-healthy behaviors.

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Section: Promoting Successful Cognitive Agingmentioning

confidence: 99%

Promoting Successful Cognitive Aging: A Ten-Year Update

Krivanek

Gale

McFeeley

et al. 2021

JAD

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“…Retinal arteriolar central re ex to vessel width ratio in digital retinal photographs was signi cantly higher in APOE ε4 allele carriers (46), hence the retina may allow for noninvasive monitoring of the effects of APOE ε4 on the cerebrovascular disease. Similarly, as targeting vascular risk factors is being considered in AD prevention trials (50), retinal vascular assessments could offer a window for assessing the response to various interventions.…”

Section: Introductionmentioning

confidence: 99%

Integrated Retinal Amyloid Burden With Retinal Venular Tortuosity Predicts Verbal Memory Impairment

Dumitrascu

Rosenberry

Sherman

et al. 2021

Preprint

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INTRODUCTION: Retinal imaging is a non-invasive tool to study retinal vasculature and neurodegeneration. Patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD)-related cognitive disorder exhibit both retinal vascular abnormalities and intraretinal accumulation of amyloid beta-protein (Aβ) plaque. Curcumin-enhanced retinal fluorescence imaging (CRFI) was recently translated as a safe imaging tool for retinal Aβ plaque quantification, holding promise as an early-stage pathological biomarker of AD. In this exploratory study, we sought to determine whether retinal vascular features combined with retinal amyloid burden correlate with the neurocognitive status.METHODS: We used scanning laser ophthalmoscopy to assess quantitative CRFI in a cohort of patients with cognitive impairment that underwent standard neuropsychological testing. Retinal blood vessels were segmented in a predefined circumpapillary region of interest. For each centerline, vessel tortuosity index, vessel inflection index and branching angle was quantified. Additionally, we automatically quantified retinal amyloid count in the supero-temporal quadrant and its subregions: posterior pole, proximal mid-periphery, and distal mid-periphery. Investigators performing quantifications were blinded to the subjects’ clinical characteristics. Linear regression models were used to assess the correlations between retinal vascular and amyloid parameters and cognitive domain Z-scores.RESULTS: In this pilot study, 34 subjects underwent automated retinal amyloid imaging and 29 subjects (55% female, mean age 64±6 years) had the combined retinal amyloid and peripapillary vascular analysis. Eleven subjects had normal cognition, 15 MCI, 2 probable AD and 1 non-AD dementia. CRFI was increased in individuals with impaired versus normal cognitive function (p 0.0012). Venous VTI was the most significant vascular parameter that differ across levels of CDR. Branching angle correlated with amyloid count in the distal mid-periphery (p=0.03), whereas vessel inflexion index correlated with posterior pole amyloid count (p=0.02). The combined proximal mid-periphery amyloid count – venous tortuosity index was found to exhibit highly significant group differences between cognitively impaired and cognitively normal subjects (0.49 ± 1.1 vs 0.91 ± 1.4, p=0.006). The combined proximal mid-periphery amyloid-venous tortuosity index also correlated with verbal memory (Wechsler Memory Scale-IV; p=0.001) and cognitive-related quality of life (SF-36 mental component score Z-scores; p=0.039).CONCLUSION: Retinal venular tortuosity discriminates across cognitive scores and in combination with proximal mid-periphery amyloid count predicts verbal memory and cognitive-related quality-of-life. Future research is needed to confirm the clinical utility of this integrated retinal imaging-based methodology.

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“…When examining the separate components of the risk score, it was found that body mass index, treatment with antihypertensive medication, systolic blood pressure and smoking status all significantly contributed to this effect [ 99 ]. Another study including controls with a positive family history for sporadic AD found no effect of vascular risk factors on entorhinal tau burden [ 58 ]. A large study in 434 controls did not find an association between white mater hyperintensities on MRI and increased [ 18 F]flortaucipir retention [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

Clinical validity of increased cortical uptake of [18F]flortaucipir on PET as a biomarker for Alzheimer’s disease in the context of a structured 5-phase biomarker development framework

Wolters

Dodich

Boccardi

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose In 2017, the Geneva Alzheimer’s disease (AD) Biomarker Roadmap initiative adapted the framework of the systematic validation of oncological diagnostic biomarkers to AD biomarkers, with the aim to accelerate their development and implementation in clinical practice. With this work, we assess the maturity of [18F]flortaucipir PET and define its research priorities. Methods The level of maturity of [18F]flortaucipir was assessed based on the AD Biomarker Roadmap. The framework assesses analytical validity (phases 1–2), clinical validity (phases 3–4), and clinical utility (phase 5). Results The main aims of phases 1 (rationale for use) and 2 (discriminative ability) have been achieved. [18F]Flortaucipir binds with high affinity to paired helical filaments of tau and has favorable kinetic properties and excellent discriminative accuracy for AD. The majority of secondary aims of phase 2 were fully achieved. Multiple studies showed high correlations between ante-mortem [18F]flortaucipir PET and post-mortem tau (as assessed by histopathology), and also the effects of covariates on tracer binding are well studied. The aims of phase 3 (early detection ability) were only partially or preliminarily achieved, and the aims of phases 4 and 5 were not achieved. Conclusion Current literature provides partial evidence for clinical utility of [18F]flortaucipir PET. The aims for phases 1 and 2 were mostly achieved. Phase 3 studies are currently ongoing. Future studies including representative MCI populations and a focus on healthcare outcomes are required to establish full maturity of phases 4 and 5.

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Association of Vascular Risk Factors With β-Amyloid Peptide and Tau Burdens in Cognitively Unimpaired Individuals and Its Interaction With Vascular Medication Use

Cited by 39 publications

References 57 publications

Promoting Successful Cognitive Aging: A Ten-Year Update

Promoting Successful Cognitive Aging: A Ten-Year Update

Integrated Retinal Amyloid Burden With Retinal Venular Tortuosity Predicts Verbal Memory Impairment

Clinical validity of increased cortical uptake of [18F]flortaucipir on PET as a biomarker for Alzheimer’s disease in the context of a structured 5-phase biomarker development framework

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