ApoB, small-dense LDL-C, Lp(a), LpPLA2 activity, and cognitive change

Yashashwi Pokharel, Farah Mouhanna, Vijay Nambi, Salim S. Virani, Ron Hoogeveen, Alvaro Alonso, Gerardo Heiss, Josef Coresh, Thomas Mosley, Rebecca F Gottesman, Christie M. Ballantyne, Melinda C. Power

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To examine the association of specific lipoproteins/inflammatory enzyme with cognitive change. METHODS: We examined the association of apolipoprotein B (ApoB), small-dense low-density lipoprotein cholesterol (sdLDL-C), lipoprotein (a) (Lp[a]), and lipoprotein-associated phospholipase A2 (LpPLA2) activity with 15-year change in Delayed Word Recall Test, Digit Symbol Substitution Test (DSST), Word Fluency Test (WFT), and overall summary score in 9,350 participants in the Atherosclerosis Risk in Communities study. We assessed interaction by race, sex, education, APOE ε4 status, and statin use. We also addressed questions of informative missingness, the role of stroke, and the influence of fasting status. RESULTS: The mean (SD) age was 63.4 (5.7) years; 56.4% were women and 17.4% were black. We observed faster cognitive decline on DSST and global z scores with every 10-mg/dL higher sdLDL-C level (Δ DSST z score, -0.010; 95% confidence interval [CI] -0.017, -0.002 and Δ global z score, -0.011; -0.021, -0.001) and the highest vs the lowest ApoB quintiles (Δ DSST z score, -0.092; -0.0164, -0.019 and Δ global z score, -0.101; -0.200, -0.002). Association for the ApoB quintiles with Δ global z score (-0.10) was comparable with that of having 1 APOE ε4 allele (-0.11). Higher Lp(a) was associated with slower decline in DSST, WFT, and global z scores. LpPLA2 activity was not associated with cognitive change. Results were similar in sensitivity analyses. The associations of sdLDL-C or Lp(a) on cognitive change were more pronounced in statin users. CONCLUSIONS: Optimal control of atherogenic lipoproteins such as ApoB and sdLDL-C in midlife for cardiovascular health may also benefit late-life cognitive health.

Original languageEnglish (US)
Pages (from-to)e2580-e2593
JournalNeurology
Volume92
Issue number22
DOIs
StatePublished - May 28 2019

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1-Alkyl-2-acetylglycerophosphocholine Esterase
Apolipoproteins B
LDL Cholesterol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipoproteins
Lipoprotein(a)
Sex Education
Health
Fasting
Atherosclerosis
Stroke
Alleles
Confidence Intervals
oxidized low density lipoprotein
Enzymes

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Pokharel, Y., Mouhanna, F., Nambi, V., Virani, S. S., Hoogeveen, R., Alonso, A., ... Power, M. C. (2019). ApoB, small-dense LDL-C, Lp(a), LpPLA2 activity, and cognitive change. Neurology, 92(22), e2580-e2593. https://doi.org/10.1212/WNL.0000000000007574

ApoB, small-dense LDL-C, Lp(a), LpPLA2 activity, and cognitive change. / Pokharel, Yashashwi; Mouhanna, Farah; Nambi, Vijay; Virani, Salim S.; Hoogeveen, Ron; Alonso, Alvaro; Heiss, Gerardo; Coresh, Josef; Mosley, Thomas; Gottesman, Rebecca F; Ballantyne, Christie M.; Power, Melinda C.

In: Neurology, Vol. 92, No. 22, 28.05.2019, p. e2580-e2593.

Research output: Contribution to journalArticle

Pokharel, Y, Mouhanna, F, Nambi, V, Virani, SS, Hoogeveen, R, Alonso, A, Heiss, G, Coresh, J, Mosley, T, Gottesman, RF, Ballantyne, CM & Power, MC 2019, 'ApoB, small-dense LDL-C, Lp(a), LpPLA2 activity, and cognitive change', Neurology, vol. 92, no. 22, pp. e2580-e2593. https://doi.org/10.1212/WNL.0000000000007574
Pokharel Y, Mouhanna F, Nambi V, Virani SS, Hoogeveen R, Alonso A et al. ApoB, small-dense LDL-C, Lp(a), LpPLA2 activity, and cognitive change. Neurology. 2019 May 28;92(22):e2580-e2593. https://doi.org/10.1212/WNL.0000000000007574
Pokharel, Yashashwi ; Mouhanna, Farah ; Nambi, Vijay ; Virani, Salim S. ; Hoogeveen, Ron ; Alonso, Alvaro ; Heiss, Gerardo ; Coresh, Josef ; Mosley, Thomas ; Gottesman, Rebecca F ; Ballantyne, Christie M. ; Power, Melinda C. / ApoB, small-dense LDL-C, Lp(a), LpPLA2 activity, and cognitive change. In: Neurology. 2019 ; Vol. 92, No. 22. pp. e2580-e2593.
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AU - Pokharel, Yashashwi

AU - Mouhanna, Farah

AU - Nambi, Vijay

AU - Virani, Salim S.

AU - Hoogeveen, Ron

AU - Alonso, Alvaro

AU - Heiss, Gerardo

AU - Coresh, Josef

AU - Mosley, Thomas

AU - Gottesman, Rebecca F

AU - Ballantyne, Christie M.

AU - Power, Melinda C.

PY - 2019/5/28

Y1 - 2019/5/28

N2 - OBJECTIVE: To examine the association of specific lipoproteins/inflammatory enzyme with cognitive change. METHODS: We examined the association of apolipoprotein B (ApoB), small-dense low-density lipoprotein cholesterol (sdLDL-C), lipoprotein (a) (Lp[a]), and lipoprotein-associated phospholipase A2 (LpPLA2) activity with 15-year change in Delayed Word Recall Test, Digit Symbol Substitution Test (DSST), Word Fluency Test (WFT), and overall summary score in 9,350 participants in the Atherosclerosis Risk in Communities study. We assessed interaction by race, sex, education, APOE ε4 status, and statin use. We also addressed questions of informative missingness, the role of stroke, and the influence of fasting status. RESULTS: The mean (SD) age was 63.4 (5.7) years; 56.4% were women and 17.4% were black. We observed faster cognitive decline on DSST and global z scores with every 10-mg/dL higher sdLDL-C level (Δ DSST z score, -0.010; 95% confidence interval [CI] -0.017, -0.002 and Δ global z score, -0.011; -0.021, -0.001) and the highest vs the lowest ApoB quintiles (Δ DSST z score, -0.092; -0.0164, -0.019 and Δ global z score, -0.101; -0.200, -0.002). Association for the ApoB quintiles with Δ global z score (-0.10) was comparable with that of having 1 APOE ε4 allele (-0.11). Higher Lp(a) was associated with slower decline in DSST, WFT, and global z scores. LpPLA2 activity was not associated with cognitive change. Results were similar in sensitivity analyses. The associations of sdLDL-C or Lp(a) on cognitive change were more pronounced in statin users. CONCLUSIONS: Optimal control of atherogenic lipoproteins such as ApoB and sdLDL-C in midlife for cardiovascular health may also benefit late-life cognitive health.

AB - OBJECTIVE: To examine the association of specific lipoproteins/inflammatory enzyme with cognitive change. METHODS: We examined the association of apolipoprotein B (ApoB), small-dense low-density lipoprotein cholesterol (sdLDL-C), lipoprotein (a) (Lp[a]), and lipoprotein-associated phospholipase A2 (LpPLA2) activity with 15-year change in Delayed Word Recall Test, Digit Symbol Substitution Test (DSST), Word Fluency Test (WFT), and overall summary score in 9,350 participants in the Atherosclerosis Risk in Communities study. We assessed interaction by race, sex, education, APOE ε4 status, and statin use. We also addressed questions of informative missingness, the role of stroke, and the influence of fasting status. RESULTS: The mean (SD) age was 63.4 (5.7) years; 56.4% were women and 17.4% were black. We observed faster cognitive decline on DSST and global z scores with every 10-mg/dL higher sdLDL-C level (Δ DSST z score, -0.010; 95% confidence interval [CI] -0.017, -0.002 and Δ global z score, -0.011; -0.021, -0.001) and the highest vs the lowest ApoB quintiles (Δ DSST z score, -0.092; -0.0164, -0.019 and Δ global z score, -0.101; -0.200, -0.002). Association for the ApoB quintiles with Δ global z score (-0.10) was comparable with that of having 1 APOE ε4 allele (-0.11). Higher Lp(a) was associated with slower decline in DSST, WFT, and global z scores. LpPLA2 activity was not associated with cognitive change. Results were similar in sensitivity analyses. The associations of sdLDL-C or Lp(a) on cognitive change were more pronounced in statin users. CONCLUSIONS: Optimal control of atherogenic lipoproteins such as ApoB and sdLDL-C in midlife for cardiovascular health may also benefit late-life cognitive health.

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