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. 2021 Apr 18;11(4):718.
doi: 10.3390/diagnostics11040718.

Dual Effect of PER2 C111G Polymorphism on Cognitive Functions across Progression from Subjective Cognitive Decline to Mild Cognitive Impairment

Salvatore Mazzeo  1   2 , Valentina Bessi  1 , Silvia Bagnoli  1 , Giulia Giacomucci  1 , Juri Balestrini  1 , Sonia Padiglioni  3   4 , Giulia Tomaiuolo  1 , Assunta Ingannato  1 , Camilla Ferrari  1 , Laura Bracco  1 , Sandro Sorbi  1   2 , Benedetta Nacmias  1   2
Affiliations

Dual Effect of PER2 C111G Polymorphism on Cognitive Functions across Progression from Subjective Cognitive Decline to Mild Cognitive Impairment

Salvatore Mazzeo et al. Diagnostics (Basel). .

Abstract

Background: Periodic circadian protein homolog 2 (PER2) has a role in the intracellular signaling pathways of long-term potentiation and has implications for synaptic plasticity. We aimed to assess the association of PER2 C111G polymorphism with cognitive functions in subjective cognitive decline (SCD).

Methods: Forty-five SCD patients were included in this study. All participants underwent extensive neuropsychological investigation, analysis of apolipoprotein E (APOE) and PER2 genotypes, and neuropsychological follow-up every 12 or 24 months for a mean time of 9.87 ± 4.38 years.

Results: Nine out of 45 patients (20%) were heterozygous carriers of the PER2 C111G polymorphism (G carriers), while 36 patients (80%) were not carriers of the G allele (G non-carriers). At baseline, G carriers had a higher language composite score compared to G non-carriers. During follow-up, 15 (34.88%) patients progressed to mild cognitive impairment (MCI). In this group, we found a significant interaction between PER2 G allele and follow-up time, as carriers of G allele showed greater worsening of executive function, visual-spatial ability, and language composite scores compared to G non-carriers.

Conclusions: PER2 C111G polymorphism is associated with better language performance in SCD patients. Nevertheless, as patients progress to MCI, G allele carriers showed a greater worsening in cognitive performance compared to G non-carriers. The effect of PER2 C111G polymorphism depends on the global cognitive status of patients.

Keywords: Alzheimer’s disease; PER2 gene; cognitive reserve; executive function; language; neuropsychology; subjective cognitive decline; visual–spatial ability.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Comparison of composite score for each cognitive domain between G carriers and G non-carriers. Values quoted in the axis are median values. Language composite score (*) was higher in G carriers as compared to G non-carriers (0.25 [IQR 0.94] vs. 0.62 [IQR 0.52], p = 0.018).
Figure 2
Figure 2
Longitudinal association of PER2 genotype with composite scores for executive function (A), language (B), and visual–spatial ability (C) in the “progressed SCD” (pSCD) group. On the x-axis, T0 indicates the baseline evaluation and T1 indicates the last neuropsychological evaluation. On the y-axis, median of composite scores (z-score) for each cognitive domain are reported.
See this image and copyright information in PMC

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