DOI: 10.1002/alz.076084 ISSN: 1552-5260

Association of creatine kinase with cognition, neuroimaging, and Alzheimer’s pathology

Yu‐tong Wang, Pei‐yang Gao
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Creatine kinase (CK) and its related metabolites are known to imply cardiovascular system disease, whereas the cardiovascular metabolic state is associated with the state of cognitive well‐being of the brain. However, the extent to which CK levels is related with cognitive impairment has not been revealed.


The Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were used for this study. We first investigated the intergroup difference of participants demographic, cognitive status, Alzheimer’s disease (AD) diagnosis, and cerebrospinal fluid (CSF) AD pathology biomarkers. Next, we conducted to use liner regression model to examine the association of CK with CSF AD pathology biomarkers, cognition, and brain structure. Last, mediation analyses were utilized to explore whether the association between CK and cognition were mediated by CSF AD pathology biomarkers.


A total of 1,607 participants (mean age were 73.82±7.23 and 55.76% were male) from the ADNI database were involved in this cross‐sectional study. We found a significant difference through age, gender, AD diagnosis, and cognitive status subgroups in intergroup difference analysis (P<0.05). Meanwhile, significant association of lower level of CK with decreased level of β‐amyloid1‐42 (Aβ; β = 0.069, P = 0.040) and increased level of phosphorylated tau (P‐tau; β = ‐0.084, P = 0.007), and total‐tau (T‐tau; β = ‐0.071, P = 0.021), respectively. Liner regression analysis also indicated that the lower level of CK was associated with worse cognition (Mini‐Mental State Examination: β = 0.059, P = 0.021; Alzheimer’s Disease Assessment Scale: β = ‐0.065, P = 0.012), however not to brain structure. Moreover, mediation analysis identified CSF AD pathology biomarkers mediated the association between level of CK and cognition.


Our findings offered detailed proof to advise that the lower level of CK was significantly associated with poor cognition and it might be mediated by CSF AD pathology biomarkers. For future research, it is necessary to identify the precise reason and process by which changed levels of CK impact cognition.

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