#1

Crush your LDL levels to slash your dementia risk. Take your statins, kids.

Low-density lipoprotein cholesterol levels and risk of incident dementia: a distributed network analysis using common data models

“Conclusion Low LDL-C levels (<70 mg/dL (<1.8 mmol/L)) are significantly associated with a reduced risk of dementia, including ADRD, with statin therapy providing additional protective effects. These findings support the necessity of targeted lipid management as a preventive strategy against dementia, indicating the importance of personalised treatment approaches.”

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#2

It makes sense. Especially for the prevention of vascular dementia. :slight_smile:

#3

The title of this thread says the opposite of what the study says:

LDL-C levels <70 mg/dL (<1.8 mmol/L) were linked to a 26% decreased risk of all-cause dementia and a 28% decreased risk of ADRD, compared with having LDL-C levels ≥130 mg/dL (≥3.4 mmol/L) in cohorts matched at 1:1 ratio (HR 0.74, 95% CI 0.70 to 0.78 for all-cause dementia, and HR 0.72, 95% CI 0.67 to 0.77 for ADRD) (table 2 and figure 3). Furthermore, LDL-C levels <55 mg/dL (<1.4 mmol/L) were linked to an 18% reduced risk of all-cause dementia and ADRD compared with LDL-C levels ≥130 mg/dL (>3.4 mmol/L) (HR 0.82, 95% CI 0.77 to 0.88, and HR 0.82, 95% CI 0.76 to 0.89, respectively)
However, LDL-C levels <30 mg/dL (<0.8 mmol/L) did not exhibit reduced dementia risk compared with the LDL-C ≥130 mg/dL (≥3.4 mmol/L) group.
Our findings support the notion of an inverted J-shaped relationship, as we observed that LDL-C levels below 30 mg/dL (0.8 mmol/L) did not show a reduced risk of dementia compared with levels >130 mg/dL (>3.4 mmol/L), contrary to what is typically observed with LDL-C levels <55 mg/dL (<1.4 mmol/L) or 70 mg/dL (1.8 mmol/L). This finding suggests that LDL-C levels <30 mg/dL (<0.8 mmol/L) do not significantly increase dementia risk. However, if there is any protective effect, it appears to be minimal, thereby validating the consistency observed in the results.
Within comparable LDL-C level categories, statin use significantly reduced dementia risk in groups with LDL-C levels <70 mg/dL (<1.8 mmol/L) and >130 mg/dL (>3.4 mmol/L). This observation suggests that the effectiveness of statins in preventing dementia may not only depend on achieving specific LDL-C thresholds. However, the reduced effectiveness of statins when LDL-C levels are <55 mg/dL (<1.4 mmol/L) remains unexplained, with factors such as well-managed health behaviours and nutritional status possibly playing a role. This insightful understanding of how statin use interacts with LDL-C levels emphasises the need for personalised statin prescriptions, focusing on achieving LDL-C levels that offer the maximum cognitive benefits.

So going below 55 mg/dL seems detrimental. Or maybe those below 55 mg/dL are using high–dose statin instead of low–dose statin + non–statin drug(s)?

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#4

Confirmed by Mendelian randomization: Efficacy and safety of low levels of low-density lipoprotein cholesterol: trans-ancestry linear and non-linear Mendelian randomization analyses 2023

Going below 70 mg/dL increases the dementia risk.

(Although MR might not reflect therapy here, as they’re lifelong + affect brain levels differently?)

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#5

Wow, just when it was looking like slashing LDL to 0 was totally fine, we get this.

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#6

It’s not surprising. Cholesterol is essential to the brain. Slashing LDL to near zero probably can’t be done without shutting off its supply and circulation in a major systemic way that would affect the brain. It’s very much an optimization game.

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#7

They don’t mention if the people were using statins or any type of pharmacology from what I’m seeing. Is it possible that low LDL that is caused naturally without driving it down via pharmacology is worse?

#8

It’s not what the study showed, it was that every 1 mg/dl increase in LDL-C when below 70 mg/dl lead to a 25% decrease risk of dementia – it’s not believable, that’s a 80% reduction for a 5 mg/dl increase.

It wasn’t detrimental, there just wasn’t any statistical significant difference, which can be expected when measuring at the 5th percentile LDL-C or below.

Serum LDL-C is totally separate from brain cholesterol and apoB that contains e.g LDL-C can’t cross the BBB. It just mostly goes to the liver.

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#9

Lower ApoB with very low LDL to a level where you negate ASCVD. (no plaque in arteries) + Dementia Dr Attia states that using 10 mg Crestor + 10 mg Ezetimiba should lower apoB to 40-50 rage. He also takes injections of PCSK9 to go last mile to 30-40 mg/DL, 3 Drugs he takes in video at 02:50 (PCSK9 + NEXLIZET is a combination of 2 medicines, bempedoic acid and ezetimibe. Expensive drugs. You are taking ASCVD (Atherosclerotic Cardiovascular Disease) off the table which is huge. My LDL is 49, but apoB is 68. Hope to get apoB to 40-50. ApoB in 30-40 mg/DL is same as a 5 yo child without any plaque in arteries. With these 3 drugs one should have a very low LDL and apoB levels. Possibly even reverse plaque in arteries. Sigificant reduced chance for developing Dementia and ASCVD.

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