TY - JOUR
T1 - Plasma Klotho and Cognitive Decline in Older Adults
T2 - Findings From the InCHIANTI Study
AU - Shardell, Michelle
AU - Semba, Richard D.
AU - Rosano, Caterina
AU - Kalyani, Rita R.
AU - Bandinelli, Stefania
AU - Chia, Chee W.
AU - Ferrucci, Luigi
N1 - Funding Information:
This study was funded by grants from the National Institutes of Health R01AG027012, R01HL111271, R21HL112662 (Dr. Semba), K23DK093583 (Dr. Kalyani); National Institute on Aging contracts 263MD9164 (Dr. Ferrucci) and 263 MD 821336, N01-AG-1-1, N01-AG-10211, and N01-AG-5-0002 (Dr. Bandinelli); and the Intramural Research Program of the National Institute on Aging, NIH (Drs. Ferrucci and Shardell).
Publisher Copyright:
© 2015, Oxford University Press. All rights reserved.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Background. The hormone klotho, encoded by the gene klotho, is primarily expressed in the kidney and choroid plexus of the brain. Higher klotho concentrations and certain genetic variants of klotho have been linked to better cognition; however, it is unknown whether klotho relates prospectively to slower cognitive decline in older adults. Methods: Plasma klotho was measured in 833 participants aged 55 or older without dementia enrolled in InCHIANTI, a prospective cohort study comprising Italian adults. Cognition was measured by Mini-Mental State Examination (MMSE) and Trail-Making Tests A and B (Trails A and Trails B) at enrollment and at 3 and 6 years after enrollment. We assessed whether klotho concentrations measured at the 3-year visit related to cognition and cognitive decline. Results: Each additional natural logarithm of klotho (pg/mL) was associated with 35% lower risk of meaningful decline in MMSE, defined as decline exceeding three points (relative risk = 0.65; 95% confidence interval 0.45, 0.95; p value =. 02), and 0.75-point smaller average 3-year decline (baseline to 3-year visit) in MMSE (95% confidence interval 0.02, 1.48; p value =. 04). No statistically significant associations were found between klotho and declining Trails A (relative risk = 0.99; 95% confidence interval 0.75, 1.32; p value =. 97) and B (relative risk = 1.02; 95% confidence interval 0.84, 1.24; p value =. 82). Conclusions: Higher plasma klotho concentrations were associated with lower risk of meaningful decline and smaller average decline in MMSE. We did not observe such findings with Trails A and B, perhaps because they test executive function and motor skills, whereas MMSE measures global cognition. Future studies should investigate mechanisms through which klotho may affect domain-specific cognitive changes.
AB - Background. The hormone klotho, encoded by the gene klotho, is primarily expressed in the kidney and choroid plexus of the brain. Higher klotho concentrations and certain genetic variants of klotho have been linked to better cognition; however, it is unknown whether klotho relates prospectively to slower cognitive decline in older adults. Methods: Plasma klotho was measured in 833 participants aged 55 or older without dementia enrolled in InCHIANTI, a prospective cohort study comprising Italian adults. Cognition was measured by Mini-Mental State Examination (MMSE) and Trail-Making Tests A and B (Trails A and Trails B) at enrollment and at 3 and 6 years after enrollment. We assessed whether klotho concentrations measured at the 3-year visit related to cognition and cognitive decline. Results: Each additional natural logarithm of klotho (pg/mL) was associated with 35% lower risk of meaningful decline in MMSE, defined as decline exceeding three points (relative risk = 0.65; 95% confidence interval 0.45, 0.95; p value =. 02), and 0.75-point smaller average 3-year decline (baseline to 3-year visit) in MMSE (95% confidence interval 0.02, 1.48; p value =. 04). No statistically significant associations were found between klotho and declining Trails A (relative risk = 0.99; 95% confidence interval 0.75, 1.32; p value =. 97) and B (relative risk = 1.02; 95% confidence interval 0.84, 1.24; p value =. 82). Conclusions: Higher plasma klotho concentrations were associated with lower risk of meaningful decline and smaller average decline in MMSE. We did not observe such findings with Trails A and B, perhaps because they test executive function and motor skills, whereas MMSE measures global cognition. Future studies should investigate mechanisms through which klotho may affect domain-specific cognitive changes.
KW - Biomarkers
KW - Cognition
KW - Epidemiology
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U2 - 10.1093/gerona/glv140
DO - 10.1093/gerona/glv140
M3 - Article
C2 - 26297657
AN - SCOPUS:84965142656
SN - 1079-5006
VL - 71
SP - 677
EP - 682
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 5
ER -