KIBRA T allele influences memory performance and progression of cognitive decline: a 7-year follow-up study in subjective cognitive decline and mild cognitive impairment

Neurol Sci. 2019 Aug;40(8):1559-1566. doi: 10.1007/s10072-019-03866-8. Epub 2019 Apr 5.

Abstract

KIBRA is a signal transducer protein, mainly expressed in the kidney and brain. A single-nucleotide polymorphism (SNP rs17070145, T → C exchange) has been linked to different cognitive function. In 2008, we studied 70 subjects who complained of subjective cognitive decline (SCD) and found that CT/TT carriers performed worse than CC carriers on a long-term memory test. We followed up the 70 SCD subjects and also 31 subjects affected by mild cognitive impairment (MCI) for a mean follow-up time of 7 years, during which 16 SCD subjects progressed to MCI and 14 MCI subjects progressed to Alzheimer's disease (AD). Carrying the T allele was associated with MCI and with a two times-higher risk of developing MCI than CC carriers. In the SCD sample, CT/TT carriers showed a greater worsening on Rivermead Behavioral Memory Test (RBMT) compared to CC carriers. In the MCI sample, CT/TT carriers performed worse than CC carriers on RBMT. There is a lack of consensus on the effect of KIBRA gene variants on cognitive performances in episodic memory and on the risk of AD. Our results confirm a role of T allele on progression of cognitive decline.

Keywords: Alzheimer’s disease; ApoE; KIBRA; Mild cognitive impairment; Neuropsychology; Subjective cognitive decline.

MeSH terms

  • Aged
  • Alleles
  • Cognitive Dysfunction / genetics*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Genotype
  • Heterozygote
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Memory, Long-Term / physiology
  • Middle Aged
  • Polymorphism, Single Nucleotide

Substances

  • Intracellular Signaling Peptides and Proteins
  • WWC1 protein, human