Abstract
OBJECTIVE:
Vascular risk factors like hyperlipidemia may adversely affect brain function. We hypothesized that increased serum triglycerides are associated with decreased executive function and memory in nondemented elderly subjects. We also researched possible vascular mediators and white matter microstructure as assessed with diffusion tensor imaging (DTI).
DESIGN/METHOD:
Participants were 251 nondemented elderly adults (54% male) with a mean age of 78 (SD = 6.4; range: 62-94) years and a mean education of 15.6 (SD = 2.9; range: 8-23) years. Fasting blood samples were used to detect serum triglyceride and low-density lipoprotein (LDL) levels along with ApoE4 status. DTI was used to determine whole brain fractional anisotropy (FA). Composite executive and memory scores were derived from item response theory. Clinical Dementia Rating (CDR) scores provided informant-based measures of daily functioning.
RESULTS:
Triglyceride levels were inversely correlated with executive function, but there was no relationship with memory. Controlling for age, gender, and education did not affect this correlation. This relationship persisted after controlling for vascular risk factors like LDL, total cholesterol, CDR and ApoE4 status. Lastly, adding whole-brain FA to the model did not affect the correlation between triglycerides and executive function.
CONCLUSION:
Triglyceride levels are inversely correlated with executive function in nondemented elderly adults after controlling for age, education, gender, total cholesterol, LDL, ApoE4 status, CDR, and white-matter microstructure. The fact that the effect of triglycerides on cognition was not clearly mediated by vascular risks or cerebrovascular injury raises questions about widely held assumptions of how triglycerides might impact cognition function. (PsycINFO Database Record
...from "associated with..." to "...inversely correlated with..." to "...effect of triglycerides on cognition..."
Whereas "effect of" is possible, looks like they jump to conclusions. Why isn't the obvious likely - elevated TG's are associated with reduced insulin sensitivity which is the underlying possible driving cause of impaired brain health?
Russ
E3/4 Eat whole, real, flavorful food - fresh and in season... and mix it up once in a while.
...from "associated with..." to "...inversely correlated with..." to "...effect of triglycerides on cognition..."
Whereas "effect of" is possible, looks like they jump to conclusions. Why isn't the obvious likely - elevated TG's are associated with reduced insulin sensitivity which is the underlying possible driving cause of impaired brain health? [Emphasis added]
Just a little skim and some fun here, but taking you for your word Russ, it seems you're relying on an association as well? Or maybe a causal link between insulin sensitivity and higher TG is commonly accepted and you were casual with your wording there?
Thanks for keeping us thinking critically
ApoE 3/4 > Thanks in advance for any responses made to my posts.
...from "associated with..." to "...inversely correlated with..." to "...effect of triglycerides on cognition..."
Whereas "effect of" is possible, looks like they jump to conclusions. Why isn't the obvious likely - elevated TG's are associated with reduced insulin sensitivity which is the underlying possible driving cause of impaired brain health? [Emphasis added]
Just a little skim and some fun here, but taking you for your word Russ, it seems you're relying on an association as well? Or maybe a causal link between insulin sensitivity and higher TG is commonly accepted and you were casual with your wording there?
Thanks for keeping us thinking critically
Indeed important to be clear. Was trying to say that high TG's may not mechanistically cause reduced cognition per-se. However, it seems quite plausible that reduced insulin sensitivity causes both an increase in TG's and a reduction in cognition (thus an association).
Russ
Russ
E3/4 Eat whole, real, flavorful food - fresh and in season... and mix it up once in a while.
Fascinating new paper correlates high triglycerides at midlife to greater tau and abeta 20 years later. Additionally, high levels of HDL-P were found to be protective. Somewhat paradoxically, increased levels of medium and large LDL subfractions are associated with worsened pathology. This is the first confirmation I've seen that larger LDL particles have negative associations for us. This corroborates Dr. Ronald Kraus's (off-the-record) warning to us several years ago. I really want to read full text, but can't find...
ABSTRACT
OBJECTIVE: To evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals.
METHODS: This 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.
RESULTS: CSF 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.
CONCLUSIONS: Increased 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.
Julie G wrote:Somewhat paradoxically, increased levels of medium and large LDL subtractions are associated with worsened pathology.
Julie, it looks like the spell checker has made you sound a little negative mathematically! I'm just pleased that my cognitive abilities allow me to notice this
. Thanks for weighing in, guys.
