Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial
Abstract Background Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs). Methods Finnish Geriatric Interv...
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| Veröffentlicht in: | The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2021-03, Vol.76 (3), p.491-498 |
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| creator | Sindi, Shireen Solomon, Alina Kåreholt, Ingemar Hovatta, Iiris Antikainen, Riitta Hänninen, Tuomo Levälahti, Esko Laatikainen, Tiina Lehtisalo, Jenni Lindström, Jaana Paajanen, Teemu Peltonen, Markku Singh Khalsa, Dharma Wolozin, Benjamin Strandberg, Timo Tuomilehto, Jaakko Soininen, Hilkka Ngandu, Tiia Kivipelto, Miia |
| description | Abstract
Background
Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs).
Methods
Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60–77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989).
Results
This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was −0.016 (0.19) in the intervention group and −0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI −0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: −0.005 (95% CI −0.010 to −0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI −0.011 to 0.264).
Conclusions
This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits.
Clinical Trials Registration Number
NCT01041989 |
| doi_str_mv | 10.1093/gerona/glaa279 |
| format | Article |
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Background
Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs).
Methods
Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60–77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989).
Results
This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was −0.016 (0.19) in the intervention group and −0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI −0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: −0.005 (95% CI −0.010 to −0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI −0.011 to 0.264).
Conclusions
This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits.
Clinical Trials Registration Number
NCT01041989</description><identifier>ISSN: 1079-5006</identifier><identifier>ISSN: 1758-535X</identifier><identifier>EISSN: 1758-535X</identifier><identifier>DOI: 10.1093/gerona/glaa279</identifier><identifier>PMID: 33175128</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Aging ; Apolipoprotein E ; Behavioral intervention ; Clinical trials ; Cognitive ability ; Dementia ; Dementia disorders ; Dementia prevention ; Executive function ; Intervention ; Long term memory ; Older adults ; Older people ; Polymerase chain reaction ; Telomeres ; THE JOURNAL OF GERONTOLOGY: Medical Sciences</subject><ispartof>The journals of gerontology. Series A, Biological sciences and medical sciences, 2021-03, Vol.76 (3), p.491-498</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.</rights><rights>Copyright Oxford University Press Mar 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c563t-82904daaa0d043045d70913a92e78ffa273bf63c99ab38305fa737e4f7ebe40e3</citedby><cites>FETCH-LOGICAL-c563t-82904daaa0d043045d70913a92e78ffa273bf63c99ab38305fa737e4f7ebe40e3</cites><orcidid>0000-0002-6614-4782 ; 0000-0002-3786-0552</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33175128$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-52068$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-194548$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:146406398$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Sindi, Shireen</creatorcontrib><creatorcontrib>Solomon, Alina</creatorcontrib><creatorcontrib>Kåreholt, Ingemar</creatorcontrib><creatorcontrib>Hovatta, Iiris</creatorcontrib><creatorcontrib>Antikainen, Riitta</creatorcontrib><creatorcontrib>Hänninen, Tuomo</creatorcontrib><creatorcontrib>Levälahti, Esko</creatorcontrib><creatorcontrib>Laatikainen, Tiina</creatorcontrib><creatorcontrib>Lehtisalo, Jenni</creatorcontrib><creatorcontrib>Lindström, Jaana</creatorcontrib><creatorcontrib>Paajanen, Teemu</creatorcontrib><creatorcontrib>Peltonen, Markku</creatorcontrib><creatorcontrib>Singh Khalsa, Dharma</creatorcontrib><creatorcontrib>Wolozin, Benjamin</creatorcontrib><creatorcontrib>Strandberg, Timo</creatorcontrib><creatorcontrib>Tuomilehto, Jaakko</creatorcontrib><creatorcontrib>Soininen, Hilkka</creatorcontrib><creatorcontrib>Ngandu, Tiia</creatorcontrib><creatorcontrib>Kivipelto, Miia</creatorcontrib><creatorcontrib>FINGER Study Group</creatorcontrib><title>Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial</title><title>The journals of gerontology. Series A, Biological sciences and medical sciences</title><addtitle>J Gerontol A Biol Sci Med Sci</addtitle><description>Abstract
Background
Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs).
Methods
Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60–77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989).
Results
This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was −0.016 (0.19) in the intervention group and −0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI −0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: −0.005 (95% CI −0.010 to −0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI −0.011 to 0.264).
Conclusions
This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits.
Clinical Trials Registration Number
NCT01041989</description><subject>Aging</subject><subject>Apolipoprotein E</subject><subject>Behavioral intervention</subject><subject>Clinical trials</subject><subject>Cognitive ability</subject><subject>Dementia</subject><subject>Dementia disorders</subject><subject>Dementia prevention</subject><subject>Executive function</subject><subject>Intervention</subject><subject>Long term memory</subject><subject>Older adults</subject><subject>Older people</subject><subject>Polymerase chain reaction</subject><subject>Telomeres</subject><subject>THE JOURNAL OF GERONTOLOGY: Medical Sciences</subject><issn>1079-5006</issn><issn>1758-535X</issn><issn>1758-535X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>D8T</sourceid><recordid>eNqFks9v0zAUxy0EYlvhyhFZ4gKCbE5sx_EOSFXGj0lFIFQQN8tNXlIXxy5O0jH-ehy1TAwJzRfbz5_3td_zF6EnKTlNiaRnLQTv9Flrtc6EvIeOU8GLhFP-7X5cEyETTkh-hE76fkOmwbOH6IjSiKVZcYx-LsH6DgLgBbh2WONyrV0L2Dis8YfRDqb2nY67hWmgH64t4Es3QNiBG4x3ePD4U4Bph0vfOjOYHeALqKxxcI7n-LN2UcD8ghqXMWYqbfEyGG0foQeNtj08Pswz9OXtm2X5Pll8fHdZzhdJxXM6JEUmCau11qQmjBLGa0FkSrXMQBRNE4umqyanlZR6RQtKeKMFFcAaAStgBOgMJXvd_gq240ptg-l0uFZeG3UIfY8rUCzPRbxihl79l78wX-fKh1b1o0ol46yI-Mu78fVG8YzkE_16T0e0g7qKbQva3kq6feLMWrV-p4QkgkkeBZ4fBIL_McYPUZ3pK7BWO_BjrzLGZZ5RSqa7nv2DbvwYXOy1yni0TkpoOpV7uqeq4Ps-QHPzmJSoyWFq7zB1cFhMePp3CTf4H0tF4MUe8OP2LrHfQrXfcA</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Sindi, Shireen</creator><creator>Solomon, Alina</creator><creator>Kåreholt, Ingemar</creator><creator>Hovatta, Iiris</creator><creator>Antikainen, Riitta</creator><creator>Hänninen, Tuomo</creator><creator>Levälahti, Esko</creator><creator>Laatikainen, Tiina</creator><creator>Lehtisalo, Jenni</creator><creator>Lindström, Jaana</creator><creator>Paajanen, Teemu</creator><creator>Peltonen, Markku</creator><creator>Singh Khalsa, Dharma</creator><creator>Wolozin, Benjamin</creator><creator>Strandberg, Timo</creator><creator>Tuomilehto, Jaakko</creator><creator>Soininen, Hilkka</creator><creator>Ngandu, Tiia</creator><creator>Kivipelto, Miia</creator><general>Oxford University Press</general><scope>TOX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><scope>AABRY</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>D8X</scope><scope>ZZAVC</scope><scope>ABAVF</scope><scope>DG7</scope><orcidid>https://orcid.org/0000-0002-6614-4782</orcidid><orcidid>https://orcid.org/0000-0002-3786-0552</orcidid></search><sort><creationdate>20210301</creationdate><title>Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial</title><author>Sindi, Shireen ; Solomon, Alina ; Kåreholt, Ingemar ; Hovatta, Iiris ; Antikainen, Riitta ; Hänninen, Tuomo ; Levälahti, Esko ; Laatikainen, Tiina ; Lehtisalo, Jenni ; Lindström, Jaana ; Paajanen, Teemu ; Peltonen, Markku ; Singh Khalsa, Dharma ; Wolozin, Benjamin ; Strandberg, Timo ; Tuomilehto, Jaakko ; Soininen, Hilkka ; Ngandu, Tiia ; Kivipelto, Miia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c563t-82904daaa0d043045d70913a92e78ffa273bf63c99ab38305fa737e4f7ebe40e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aging</topic><topic>Apolipoprotein E</topic><topic>Behavioral intervention</topic><topic>Clinical trials</topic><topic>Cognitive ability</topic><topic>Dementia</topic><topic>Dementia disorders</topic><topic>Dementia prevention</topic><topic>Executive function</topic><topic>Intervention</topic><topic>Long term memory</topic><topic>Older adults</topic><topic>Older people</topic><topic>Polymerase chain reaction</topic><topic>Telomeres</topic><topic>THE JOURNAL OF GERONTOLOGY: Medical Sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sindi, Shireen</creatorcontrib><creatorcontrib>Solomon, Alina</creatorcontrib><creatorcontrib>Kåreholt, Ingemar</creatorcontrib><creatorcontrib>Hovatta, Iiris</creatorcontrib><creatorcontrib>Antikainen, Riitta</creatorcontrib><creatorcontrib>Hänninen, Tuomo</creatorcontrib><creatorcontrib>Levälahti, Esko</creatorcontrib><creatorcontrib>Laatikainen, Tiina</creatorcontrib><creatorcontrib>Lehtisalo, Jenni</creatorcontrib><creatorcontrib>Lindström, Jaana</creatorcontrib><creatorcontrib>Paajanen, Teemu</creatorcontrib><creatorcontrib>Peltonen, Markku</creatorcontrib><creatorcontrib>Singh Khalsa, Dharma</creatorcontrib><creatorcontrib>Wolozin, Benjamin</creatorcontrib><creatorcontrib>Strandberg, Timo</creatorcontrib><creatorcontrib>Tuomilehto, Jaakko</creatorcontrib><creatorcontrib>Soininen, Hilkka</creatorcontrib><creatorcontrib>Ngandu, Tiia</creatorcontrib><creatorcontrib>Kivipelto, Miia</creatorcontrib><creatorcontrib>FINGER Study Group</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SWEPUB Högskolan i Jönköping full text</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Högskolan i Jönköping</collection><collection>SwePub Articles full text</collection><collection>SWEPUB Stockholms universitet full text</collection><collection>SWEPUB Stockholms universitet</collection><jtitle>The journals of gerontology. Series A, Biological sciences and medical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sindi, Shireen</au><au>Solomon, Alina</au><au>Kåreholt, Ingemar</au><au>Hovatta, Iiris</au><au>Antikainen, Riitta</au><au>Hänninen, Tuomo</au><au>Levälahti, Esko</au><au>Laatikainen, Tiina</au><au>Lehtisalo, Jenni</au><au>Lindström, Jaana</au><au>Paajanen, Teemu</au><au>Peltonen, Markku</au><au>Singh Khalsa, Dharma</au><au>Wolozin, Benjamin</au><au>Strandberg, Timo</au><au>Tuomilehto, Jaakko</au><au>Soininen, Hilkka</au><au>Ngandu, Tiia</au><au>Kivipelto, Miia</au><aucorp>FINGER Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial</atitle><jtitle>The journals of gerontology. Series A, Biological sciences and medical sciences</jtitle><addtitle>J Gerontol A Biol Sci Med Sci</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>76</volume><issue>3</issue><spage>491</spage><epage>498</epage><pages>491-498</pages><issn>1079-5006</issn><issn>1758-535X</issn><eissn>1758-535X</eissn><abstract>Abstract
Background
Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs).
Methods
Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60–77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989).
Results
This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was −0.016 (0.19) in the intervention group and −0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI −0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: −0.005 (95% CI −0.010 to −0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI −0.011 to 0.264).
Conclusions
This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits.
Clinical Trials Registration Number
NCT01041989</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>33175128</pmid><doi>10.1093/gerona/glaa279</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-6614-4782</orcidid><orcidid>https://orcid.org/0000-0002-3786-0552</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | The journals of gerontology. Series A, Biological sciences and medical sciences, 2021-03, Vol.76 (3), p.491-498 |
| issn | 1079-5006 1758-535X 1758-535X |
| language | eng |
| recordid | cdi_proquest_journals_2509310314 |
| source | Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection; SWEPUB Freely available online |
| subjects | Aging Apolipoprotein E Behavioral intervention Clinical trials Cognitive ability Dementia Dementia disorders Dementia prevention Executive function Intervention Long term memory Older adults Older people Polymerase chain reaction Telomeres THE JOURNAL OF GERONTOLOGY: Medical Sciences |
| title | Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial |
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