Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later

Abstract

ObjectiveTo evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals.MethodsThis is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of β-amyloid (Aβ) and tau pathologies 20 years later (mean age 73 years) were detected by quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134), Aβ (18F-flutemetamol) PET was also performed.ResultsCSF Aβ42 and Aβ PET revealed Aβ pathology in approximately 20% of the cognitively healthy population and CSF Aβ42/phosphorylated tau (p-tau) ratio indicated both Aβ and tau pathology in 16%. Higher levels of triglycerides in midlife were independently associated with abnormal CSF Aβ42 (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.03–1.75, p = 0.029) and abnormal Aβ42/p-tau ratio (OR 1.46, 95% CI 1.10–1.93; p = 0.009) adjusting for age, sex, APOE ε4, education, and multiple vascular risk factors. Triglycerides were also associated with abnormal Aβ PET in multivariable regression models, but the association was attenuated in the fully adjusted model. Increased levels of medium and large low-density lipoprotein subfractions were significantly associated with abnormal Aβ PET and large high-density lipoprotein particles were associated with decreased risk of abnormal Aβ PET.ConclusionsIncreased levels of triglycerides at midlife predict brain Aβ and tau pathology 20 years later in cognitively healthy individuals. Certain lipoprotein subfractions may also be risk factors for Aβ pathology. These findings further support an involvement of lipids in the very early stages of AD development.

Metabolic and vascular risk factors are associated with reduced cerebral blood flow and poorer midlife memory performance

“…Our findings appear at odds with one study that reported that these variables did not influence cognition over a 7-year period among non-demented adults living in their 70s (Reitz, Luchsinger, Tang, Manly, & Mayeux, 2005); however, a more recent study found that high triglycerides in midlife were associated with increased risk of AD markers, that is, protein concentrations in cerebrospinal fluid, and evidence of amyloid in tissue during 20 year follow-up imaging (Nägga et al, 2018). Our findings appear at odds with one study that reported that these variables did not influence cognition over a 7-year period among non-demented adults living in their 70s (Reitz, Luchsinger, Tang, Manly, & Mayeux, 2005); however, a more recent study found that high triglycerides in midlife were associated with increased risk of AD markers, that is, protein concentrations in cerebrospinal fluid, and evidence of amyloid in tissue during 20 year follow-up imaging (Nägga et al, 2018).…”

Vascular Risk and β‐Amyloid Are Synergistically Associated with Cortical Tau

“…[12][13][14] However, the evidence is mixed as to whether a relationship exists between vascular risk factors and Aβ burden measured concurrently in older adults, 10,12,15 with recent data from our group suggesting no relationship. [12][13][14] However, the evidence is mixed as to whether a relationship exists between vascular risk factors and Aβ burden measured concurrently in older adults, 10,12,15 with recent data from our group suggesting no relationship.…”

“…[12][13][14] However, the evidence is mixed as to whether a relationship exists between vascular risk factors and Aβ burden measured concurrently in older adults, 10,12,15 with recent data from our group suggesting no relationship. 14,16,17 Additionally, a recent autopsy study identified an association between late life systolic blood pressure and tau pathology burden. 14,16,17 Additionally, a recent autopsy study identified an association between late life systolic blood pressure and tau pathology burden.…”

Higher serum triglyceride levels are associated with Parkinson's disease mild cognitive impairment

“…TG‐induced central leptin resistance was hypothesized to be the cause . Human studies proposed that high TG compromises blood–brain barrier, and demonstrated that high TG is associated with future increased cerebral β‐amyloid/tau pathology . On the other hand, the observed association between TG and PD‐MCI could also be attributed to factors that impact both lipid metabolism and cognition, such as diet, physical activity, and genetics, which warrant further exploration.…”