Apolipoproteins and HDL cholesterol do not associate with the risk of future dementia and Alzheimer’s disease: the National Finnish population study (FINRISK)

Kim

et al. 2020

Preprint

Background: The clinical guidelines related to the primary prevention of Alzheimer’s disease (AD) have focused on the management of vascular risk factors. However, the link between vascular risk factors and AD in older adults remains unclear. This study aimed to determine the association between vascular risk factors and subsequent AD in 178,586 older adults (age: ≥65 years). Methods: Participants were recruited from 2009 through 2010 and followed up for 6 years. We assessed various vascular risk factors (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], fasting glucose [FG], systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP] and body mass index [BMI]) and their association with AD incidence, categorizing each vascular factor using current clinical guidelines. Results: AD was observed in 6.0% of participants at follow-up. All lipid profiles (TC, LDL-C, HDL-C, TG) were positively associated with the risk of AD. SBP and PP were in negative associations with AD, and DBP was positively associated with AD. BMI exhibited a negative association with AD incidence. We found no significant association between FG and AD risk. The sex difference was observed to have effects on vascular risk factors.Conclusions: In this study, we comprehensively investigated the association between eight vascular risk factors and the risk of incident AD. Our findings suggest that multiple vascular risk factors are related to the development of AD in older adults. These results can help inform future guidelines for reducing AD risk.

Section: Discussioncontrasting

confidence: 78%

Associations between vascular risk factors and subsequent Alzheimer’s disease in older adults

Kim

et al. 2020

Preprint

“…In contrast, in a National Finnish prospective population study including 13,275 subjects (age 25–74 years), HDL‐C levels were inversely associated with AD risk when adjusted for competing risks. However, this result did not provide clinical relevance to support the application of lipid as predictive marker of incident dementia …”

Section: Role Of Hdls In Neurological Diseasesmentioning

confidence: 66%

“…However, this result did not provide clinical relevance to support the application of lipid as predictive marker of incident dementia. 141 It has been shown that apoA-I obtained from the plasma macrophages of AD patients is less efficient in ABCA1 dependent cholesterol reversing transport compared to normal, suggesting alterations in the interaction between the apoA-I and the ABCA1. 135 Moreover, apoE-ε4 and apoJ are major susceptibility genes for AD 142 and have been associated with sporadic AD and familial late onset AD, as well as being a strong predictor of clinical progression in MCI.…”

Section: Dementiamentioning

confidence: 99%

Emerging roles for high‐density lipoproteins in neurodegenerative disorders

et al. 2019

Lipoproteins are the complexes of different lipids and proteins, which are devoted to the transport and clearance of lipids or lipid‐related molecules in the circulation. Lipoproteins have been found to play a crucial role in brain function and may influence myelination process. Among lipoproteins, high‐density lipoproteins (HDLs) and their major protein component, apoA‐I, are directly involved in cholesterol efflux in the brain. It has been suggested that inadequate or dysfunctional brain HDLs may contribute to cerebrovascular dysfunctions, neurodegeneration, or neurovascular instability. HDL deficiency could also promote cognitive decline through impacting on atherosclerotic risk. The focus of this review is to discuss knowledge on HDL dysregulation in neurological disorders. A better understanding on how changes in cellular HDL and apolipoprotein homeostasis affect central nervous system function may provide promising novel avenues for the treatment of specific HDL‐related neurological disorders.

“…A Swedish twin study (n=60) found that higher ApoB at baseline predicted dementia at least 3 years later, although any cause of dementia was included in this small study [53]. A pooled analysis of two Finnish prospective population-based cohort studies (n=13,275) found that baseline ApoB was not associated with incident AD or dementia 10 years later [54]. At present, the role of ApoB in the development of SVD or VaD is unclear.…”

Section: Lipid Effects On Vascular Dementiamentioning

confidence: 89%

Hypercholesterolaemia and vascular dementia

et al. 2017

Correspondence: Philip Bath (Philip.bath@nottingham.ac.uk) Vascular dementia (VaD) is the second commonest cause of dementia. Stroke is the leading cause of disability in adults in developed countries, the second major cause of dementia and the third commonest cause of death. Traditional vascular risk factors -diabetes, hypercholesterolaemia, hypertension and smoking -are implicated as risk factors for VaD. The associations between cholesterol and small vessel disease (SVD), stroke, cognitive impairment and subsequent dementia are complex and as yet not fully understood. Similarly, the effects of lipids and lipid-lowering therapy on preventing or treating dementia remain unclear; the few trials that have assessed lipid-lowering therapy for preventing (two trials) or treating (four trials) dementia found no evidence to support the use of lipid-lowering therapy for these indications. It is appropriate to treat those patients with vascular risk factors that meet criteria for lipid-lowering therapy for the primary and secondary prevention of cardiovascular and cerebrovascular events, and in line with current guidelines. Managing the individual patient in a holistic manner according to his or her own vascular risk profile is recommended. Although the paucity of randomized controlled evidence makes for challenging clinical decision making, it provides multiple opportunities for on-going and future research, as discussed here.