Russ wrote:...
"High Low-Density Lipoprotein Cholesterol Inversely Relates to Dementia in Community-Dwelling Older Adults: The Shanghai Aging Study"
https://www.frontiersin.org/articles/10 ... _hjh2bofZI
Hope someone else here has time to dissect and assess, but for now, seems to add more weight to the idea discussed here from time to time that intentionally reducing 'cholesterol' might be a bad idea for brain health.Russ
Thanks for sharing this Russ.
I don't have the skills to "dissect and assess", but did take a look at the definition of high LDL-C, as well as the authors' discussion of possible reasons, and limitations. The participants' average age was 69, which might be a little early to diagnose risk of MCI and AD. They were from what the authors describe as a high-income city (Shanghai) with "higher education and higher economic status" than rural areas. The authors used multiple measures of cognition, and cite that they designed this study to be similar to ones done in European countries, with 2 neurologists and a neuropsychologist confirming all cases of MCI and dementia. Unfortunately, while they genotyped ApoE 4, they don't provide any information on that as a separate variable. Maybe that's because the results weren't significant, or the numbers of ApoE 4 were too low to be significant.
The participants were sorted into thirds, with the following cut-offs for LDL-C:
- Low LDC-C = < 2.9 mmol/L (<112mg/dL in U.S.)
Middle LDL-C = 2.9-3.7 mmol/L (112-143 mg/dL)
High LDL-C = > 3.7 mmol/L (> 143 mg/dL)
As a comparison, the Mayo Clinic lists 100-129 mg/dL (2.6-3.3 mmol/L) as "near optimal if there is no heart disease and high if there is heart disease. They list < 100 mg/dL, which would be the lowest tertile in the Shanghai study, as optimal.
https://www.mayoclinic.org/tests-proced ... c-20384601
Here's an excerpt from the Discussion, that helpfully suggests multiple useful short-term and long-term follow-up studies.
Although the exact biological mechanism of LDL-C's potential protective effect is still unknown, we conjecture that one possibility is that high LDL-C might indicate a good nutritional status or health condition. Lower cholesterol has been found to be associated with a higher mortality in the elderly (30, 31), and it may accompany malnutrition, chronic diseases and cancer (32, 33), which in turn may positively associate with cognitive decline (34). On the other hand, because cholesterol is a major component of the brain, it is possible that decreasing cholesterol levels in the elderly is associated with cerebral atrophy, a typical anatomic syndrome of dementia (3). Another speculation is that high LDL-C could reduce neurons' impairments or facilitate compensatory repair of injured neurons (35). The inhibitions of dendrite outgrowth (36) and synaptogenesis (37), and the acceleration of neurodegeneration (38) have been observed when neurons was a short of cellular cholesterol or cholesterol supply. Besides, cholesterol plays an important role in the synthesis, transportation and metabolism of steroid hormones as well as lipid-soluble vitamins, both of which have an impact on synaptic integrity and neurotransmission (37, 39, 40). Apart from the reasons mentioned above, there is another hypothesis about selective survival: participants aged 70+ are more likely to be resistant to the adverse effects of high LDL-C or other cerebrovascular risk factors (41). For example, oldest-old individuals were found to show more variability in cognitive function (42) and to be less apt to age-related cognitive decline (43). At the same time, these participants may also be less susceptible to the benefit of high HDL-C. Further, the protective effect of HDL-C is inconsistent. Indeed, some genetic mechanisms raising plasma HDL-C did not lower risk of myocardial infraction (44) and even the Tromsø study reported that high HDL-C could increase the future risk of venous thromboembolism in female subjects (45).
There might be a possibility of a reversal causality of lipid level and dementia. Participants with dementia may be more likely to have an eating disorder, be malnourished and thus probably accompany with reduction of cholesterol level. However, the cross-sectional study design limited our ability to explore the causal effects. Further prospective studies are needed to provide the evidence to the causality. The second limitation in our study is that we could not discriminate the vascular dementia and Alzheimer's disease because not every participant's MRI was available at baseline. Third, the “snapshot” lipid profile measurements might not be good representative of the actual lipid levels.
Food for thought!
