Influence of ApoE Genotype and Clock T3111C Interaction with Cardiovascular Risk Factors on the Progression to Alzheimer's Disease in Subjective Cognitive Decline and Mild Cognitive Impairment Patients

Valentina Bessi, Juri Balestrini, Silvia Bagnoli, Salvatore Mazzeo, Giulia Giacomucci, Sonia Padiglioni, Irene Piaceri, Marco Carraro, Camilla Ferrari, Laura Bracco, Sandro Sorbi, Benedetta Nacmias, Valentina Bessi, Juri Balestrini, Silvia Bagnoli, Salvatore Mazzeo, Giulia Giacomucci, Sonia Padiglioni, Irene Piaceri, Marco Carraro, Camilla Ferrari, Laura Bracco, Sandro Sorbi, Benedetta Nacmias

Abstract

Background: Some genes could interact with cardiovascular risk factors in the development of Alzheimer's disease. We aimed to evaluate the interaction between ApoE ε4 status, Clock T3111C and Per2 C111G polymorphisms with cardiovascular profile in Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI).

Methods: We included 68 patients who underwent clinical evaluation; neuropsychological assessment; ApoE, Clock and Per2 genotyping at baseline; and neuropsychological follow-up every 12-24 months for a mean of 13 years. We considered subjects who developed AD and non-converters.

Results: Clock T3111C was detected in 47% of cases, Per2 C111G in 19% of cases. ApoE ε4 carriers presented higher risk of heart disease; Clock C-carriers were more frequently smokers than non C-carriers. During the follow-up, 17 patients progressed to AD. Age at baseline, ApoE ε 4 and dyslipidemia increased the risk of conversion to AD. ApoE ε4 carriers with history of dyslipidemia showed higher risk to convert to AD compared to ApoE ε4- groups and ApoE ε4+ without dyslipidemia patients. Clock C-carriers with history of blood hypertension had a higher risk of conversion to AD.

Conclusions: ApoE and Clock T3111C seem to interact with cardiovascular risk factors in SCD and MCI patients influencing the progression to AD.

Keywords: ApoE; Clock; alzheimer’s disease; cardiovascular risk factors; clock genes; mild cognitive impairment; subjective cognitive decline.

Conflict of interest statement

No authors report any conflicts of interest for this study.

Figures

Figure 1
Figure 1
(a) Kaplan–Meier survival analysis for comparisons of proportion of progression to AD between dyslipidemic (n = 4) and non-dyslipidemic (n = 17) patients in ApoE ε4+ carrier group. Proportion of progression was higher in dyslipidemic group (100.00%) compared to non-dyslipidemic (29.40%). The pairwise log rank comparisons showed significant difference in survival distributions for the dyslipidemic vs. non-dyslipidemic (χ2 = 4.42, p = 0.036). (b) Kaplan–Meier survival analysis for comparisons of proportion of progression to AD between dyslipidemic (n = 15) and non-dyslipidemic (n = 29) patients in ApoE ε4− carrier group. The pairwise log rank comparisons showed no significant difference in survival distributions for the dyslipidemic vs. non-dyslipidemic (χ2 = 1.92, p = 0.166). * For censored cases (non-converters), conversion time indicates follow-up time.
Figure 2
Figure 2
Kaplan–Meier survival analysis for comparisons of patients ranked according to history of dyslipidemia and ApoE genotype (non-dylipidemic/ε4−, n = 29; dyslipidemic/ε4−, n = 17; non-dylipidemic/high/ε4+, n = 15; dylipidemic/ε4+, n = 4). Proportion of progression was higher in dylipidemic/ε4+ (100.00%) compared to non-dylipidemic/ε4− (10.30%, χ2 = 25.47, p < 0.001), non-dylipidemic/ε4+ (29.40%, χ2 = 4.42, p = 0.036), and dylipidemic/ε4− (26.7%, χ2 = 7.64, p = 0.006). Proportion of progression in non-dylipidemic/ε4+ group (26.7%) was higher than non-dylipidemic/ε4− (10.3%, χ2 = 3.73, p = 0.05). * For censored cases (non converters) conversion time indicates follow-up time.
Figure 3
Figure 3
(a) Kaplan–Meier survival analysis for comparisons of proportion of progression to AD between hypertensive (n = 6) and non-hypertensive (n = 26) patients in Clock C carriers group. Proportion of progression was higher in hypertensive group (50.00%) compared to non-hypertensive (11.50%). The pairwise log rank comparisons showed significant difference in survival distributions for the hypertensive vs. non-hypertensive (χ2 = 5.77, p = 0.017). (b) Kaplan–Meier survival analysis for comparisons of proportion of progression to AD between hypertensive (n = 9) and non-hypertensive (n = 26) patients in Clock non C carriers group. The pairwise log rank comparisons showed no significant difference in survival distributions for the hypertensive vs. non-hypertensive (χ2 = 0.323, p = 0.570). * For censored cases (non converters) conversion time indicates follow-up time.

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