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. 2025 Sep;12(9):1743-1752.
doi: 10.1002/acn3.70117. Epub 2025 Jun 25.

Correlation Between Irisin and Cognitive Functions in Alzheimer Dementia

Patrizia Pignataro  1 , Manuela Dicarlo  2 , Chiara Zecca  3 , Daniele Urso  3 , Maria Teresa Dell'Abate  3 , Davide Vilella  3 , Francesco Borlizzi  3 , Roberta Zerlotin  2 , Angela Oranger  2 , Graziana Colaianni  2 , Silvia Colucci  1 , Maria Grano  2 , Giancarlo Logroscino  3
Affiliations

Correlation Between Irisin and Cognitive Functions in Alzheimer Dementia

Patrizia Pignataro et al. Ann Clin Transl Neurol. 2025 Sep.

Abstract

Objective: The myokine irisin, a recent positive mediator of exercise in the brain, shows neuroprotective functions against Alzheimer's disease (AD). The association between irisin and cognition has never been explored in a biologically defined cohort of patients. Thus, in the present study, we investigated the association of irisin with multidomain cognition in patients showing dementia-related symptomatology.

Methods: Cerebrospinal fluid (CSF) and serum irisin levels were evaluated using enzyme-linked immunoassays in a cohort of subjects with a confirmed biomarker evidence of AD, including AD (n = 82), mild cognitive impairment (MCI, n = 44), and subjective memory complaint (SMC, n = 20) patients. The results of this analysis were correlated with global cognitive efficiency assessed by Mini-Mental State Examination, and multidomain cognition evaluated by a battery of psychometric tests.

Results: Decreased CSF and serum irisin levels were observed in AD and MCI patients compared to SMC. A significant correlation has been found between irisin in the CSF and global cognitive efficiency, as well as with specific cognitive domains such as memory, executive functions, attention, visuospatial abilities, and language. For serum irisin, the correlation analysis evidenced similar results to those observed for the CSF.

Interpretation: Our results highlight the key involvement of irisin in multidomain cognition, indicating its potential role as a cognitive biomarker of AD progression.

Keywords: Alzheimer's disease; dementia; irisin; mild cognitive impairment; neurodegeneration.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Correlations between CSF (A–C) or serum (D–F) irisin levels and screening test scores. Dotted lines represent Spearman linear regressions (r and p values as indicated). Bold values highlight statistically significant correlations. AD, Alzheimer's dementia; CDT, Clock Drawing Test; CSF, cerebrospinal fluid; FAB, Frontal Assessment Battery; MCI, mild cognitive impairment; MMSE, Mini‐Mental Status Examination; SMC, subjective memory complaints.
FIGURE 2
FIGURE 2
Correlations between CSF (A–D) or serum (E–H) irisin levels and memory test scores. Dotted lines represent Spearman linear regressions (r and p values as indicated). Bold values highlight statistically significant correlations. AD, Alzheimer's dementia; CSF, cerebrospinal fluid; MCI, mild cognitive impairment; RAVLT, Rey Auditory Verbal Learning Test; ROCF, Rey–Osterrieth Complex Figure; SMC, subjective memory complaints.
FIGURE 3
FIGURE 3
Correlations between CSF (A–F) or serum (G–N) irisin levels and executive function test scores. Dotted lines represent Spearman linear regressions (r and p values as indicated). Bold values highlight statistically significant correlations. AD, Alzheimer's dementia; CSF, cerebrospinal fluid; DS‐B, Digit Span Backward test; MCI, mild cognitive impairment; SCWT, Stroop Color and Word Test; SMC, subjective memory complaints; TMT‐B, Trail Making Test Version B; VFT, Verbal Fluency Test.
FIGURE 4
FIGURE 4
Correlations between CSF (A–B) or serum (C–D) irisin levels and attention test scores. Dotted lines represent Spearman linear regressions (r and p values as indicated). Bold values highlight statistically significant correlations. AD, Alzheimer's dementia; CSF, cerebrospinal fluid; DS‐F, Digit Span Forward; MCI, mild cognitive impairment; SMC, subjective memory complaints; TMT‐A, Trail Making Test version A.
FIGURE 5
FIGURE 5
Correlations between CSF (A–B) or serum (C–D) irisin levels and visuospatial abilities's test scores. Dotted lines represent Spearman linear regressions (r and p values as indicated). Bold values highlight statistically significant correlations. AD, Alzheimer's dementia; CSF, cerebrospinal fluid; MCI, mild cognitive impairment; SMC, subjective memory complaints; VOSP, Visual Object and Space Perception.
FIGURE 6
FIGURE 6
Correlations between CSF (A) or serum (B) irisin levels and language test scores. Dotted lines represent Spearman linear regressions (r and p values as indicated). Bold values highlight statistically significant correlations. AD, Alzheimer's dementia; BNT, Boston Naming Test; CSF, cerebrospinal fluid; MCI, mild cognitive impairment; SMC, subjective memory complaints.
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