Neurocognitive impairment in type 2 diabetes: evidence for shared genetic aetiology
Aims/hypothesis Type 2 diabetes is associated with cognitive impairments, but it is unclear whether common genetic factors influence both type 2 diabetes risk and cognition. Methods Using data from 1892 Mexican-American individuals from extended pedigrees, including 402 with type 2 diabetes, we exam...
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| Veröffentlicht in: | Diabetologia 2020-05, Vol.63 (5), p.977-986 |
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| creator | Mollon, Josephine Curran, Joanne E. Mathias, Samuel R. Knowles, Emma E. M. Carlisle, Phoebe Fox, Peter T. Olvera, Rene L. Göring, Harald H. H. Rodrigue, Amanda Almasy, Laura Duggirala, Ravi Blangero, John Glahn, David C. |
| description | Aims/hypothesis
Type 2 diabetes is associated with cognitive impairments, but it is unclear whether common genetic factors influence both type 2 diabetes risk and cognition.
Methods
Using data from 1892 Mexican-American individuals from extended pedigrees, including 402 with type 2 diabetes, we examined possible pleiotropy between type 2 diabetes and cognitive functioning, as measured by a comprehensive neuropsychological test battery.
Results
Negative phenotypic correlations (
ρ
p
) were observed between type 2 diabetes and measures of attention (Continuous Performance Test [CPT d′]:
ρ
p
= −0.143,
p
= 0.001), verbal memory (California Verbal Learning Test [CVLT] recall:
ρ
p
= −0.111,
p
= 0.004) and face memory (Penn Face Memory Test [PFMT]:
ρ
p
= −0.127,
p
= 0.002; PFMT Delayed:
ρ
p
=
−0.148,
p
= 2 × 10
−
4
), replicating findings of cognitive impairment in type 2 diabetes. Negative genetic correlations (
ρ
g
) were also observed between type 2 diabetes and measures of attention (CPT d′:
ρ
g
= −0.401,
p
= 0.001), working memory (digit span backward test:
ρ
g
= −0.380,
p
= 0.005), and face memory (PFMT:
ρ
g
= −0.476,
p
= 2 × 10
−
4
; PFMT Delayed:
ρ
g
= −0.376,
p
= 0.005), suggesting that the same genetic factors underlying risk for type 2 diabetes also influence poor cognitive performance in these domains. Performance in these domains was also associated with type 2 diabetes risk using an endophenotype ranking value approach. Specifically, on measures of attention (CPT d′:
β
= −0.219,
p
= 0.005), working memory (digit span backward:
β
= −0.326,
p
= 0.035), and face memory (PFMT:
β
= −0.171,
p
= 0.023; PFMT Delayed:
β
= −0.215,
p
= 0.005), individuals with type 2 diabetes showed the lowest performance, while unaffected/unrelated individuals showed the highest performance, and those related to an individual with type 2 diabetes performed at an intermediate level.
Conclusions/interpretation
These findings suggest that cognitive impairment may be a useful endophenotype of type 2 diabetes and, therefore, help to elucidate the pathophysiological underpinnings of this chronic disease.
Data availability
The data analysed in this study is available in dbGaP:
www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001215.v2.p2
. |
| doi_str_mv | 10.1007/s00125-020-05101-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7150650</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2387615079</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-e461153c8356fc985f7c4ed153645df46f55556155699c601d73f6cbf8c701b53</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhi0EotvCH-CALHHhEhjHXwkHJFRBqVS1B0DiZnmdceoqiRc7WSn_HpctpXDAkj2S55nXM34JecHgDQPQbzMAq2UFNVQgGbBqfUQ2TPC6AlE3j8nmNl-xRn0_Isc53wAAl0I9JUe8Bqak0hvy5RKXFF3spzCHPdIw7mxII04zDROd1x3SmnbBbnHG_I7iPnQ4OaQ-JpqvbcKO9jjhHBy15YxD7Ndn5Im3Q8bnd_GEfPv08evp5-ri6uz89MNF5YQWc4VCMSa5a7hU3rWN9NoJ7MqVErLzQnlZlmJlt61TwDrNvXJb3zgNbCv5CXl_0N0t2xE7V5pOdjC7FEabVhNtMH9npnBt-rg3mklQEorA6zuBFH8smGczhuxwGOyEccmm5hLa8octL-irf9CbuKSpjFeoRpcuQbeFqg-USzHnhP6-GQbm1jNz8MwUz8wvz8xail4-HOO-5LdJBeAHIJfU1GP68_Z_ZH8CQgGieA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2387615079</pqid></control><display><type>article</type><title>Neurocognitive impairment in type 2 diabetes: evidence for shared genetic aetiology</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Mollon, Josephine ; Curran, Joanne E. ; Mathias, Samuel R. ; Knowles, Emma E. M. ; Carlisle, Phoebe ; Fox, Peter T. ; Olvera, Rene L. ; Göring, Harald H. H. ; Rodrigue, Amanda ; Almasy, Laura ; Duggirala, Ravi ; Blangero, John ; Glahn, David C.</creator><creatorcontrib>Mollon, Josephine ; Curran, Joanne E. ; Mathias, Samuel R. ; Knowles, Emma E. M. ; Carlisle, Phoebe ; Fox, Peter T. ; Olvera, Rene L. ; Göring, Harald H. H. ; Rodrigue, Amanda ; Almasy, Laura ; Duggirala, Ravi ; Blangero, John ; Glahn, David C.</creatorcontrib><description>Aims/hypothesis
Type 2 diabetes is associated with cognitive impairments, but it is unclear whether common genetic factors influence both type 2 diabetes risk and cognition.
Methods
Using data from 1892 Mexican-American individuals from extended pedigrees, including 402 with type 2 diabetes, we examined possible pleiotropy between type 2 diabetes and cognitive functioning, as measured by a comprehensive neuropsychological test battery.
Results
Negative phenotypic correlations (
ρ
p
) were observed between type 2 diabetes and measures of attention (Continuous Performance Test [CPT d′]:
ρ
p
= −0.143,
p
= 0.001), verbal memory (California Verbal Learning Test [CVLT] recall:
ρ
p
= −0.111,
p
= 0.004) and face memory (Penn Face Memory Test [PFMT]:
ρ
p
= −0.127,
p
= 0.002; PFMT Delayed:
ρ
p
=
−0.148,
p
= 2 × 10
−
4
), replicating findings of cognitive impairment in type 2 diabetes. Negative genetic correlations (
ρ
g
) were also observed between type 2 diabetes and measures of attention (CPT d′:
ρ
g
= −0.401,
p
= 0.001), working memory (digit span backward test:
ρ
g
= −0.380,
p
= 0.005), and face memory (PFMT:
ρ
g
= −0.476,
p
= 2 × 10
−
4
; PFMT Delayed:
ρ
g
= −0.376,
p
= 0.005), suggesting that the same genetic factors underlying risk for type 2 diabetes also influence poor cognitive performance in these domains. Performance in these domains was also associated with type 2 diabetes risk using an endophenotype ranking value approach. Specifically, on measures of attention (CPT d′:
β
= −0.219,
p
= 0.005), working memory (digit span backward:
β
= −0.326,
p
= 0.035), and face memory (PFMT:
β
= −0.171,
p
= 0.023; PFMT Delayed:
β
= −0.215,
p
= 0.005), individuals with type 2 diabetes showed the lowest performance, while unaffected/unrelated individuals showed the highest performance, and those related to an individual with type 2 diabetes performed at an intermediate level.
Conclusions/interpretation
These findings suggest that cognitive impairment may be a useful endophenotype of type 2 diabetes and, therefore, help to elucidate the pathophysiological underpinnings of this chronic disease.
Data availability
The data analysed in this study is available in dbGaP:
www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001215.v2.p2
.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-020-05101-y</identifier><identifier>PMID: 32016567</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Chronic illnesses ; Cognition ; Cognition - physiology ; Cognition Disorders - genetics ; Cognition Disorders - physiopathology ; Cognitive ability ; Cognitive Dysfunction - genetics ; Cognitive Dysfunction - physiopathology ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - physiopathology ; Face ; Female ; Genetic factors ; Human Physiology ; Humans ; Internal Medicine ; Male ; Medicine ; Medicine & Public Health ; Memory ; Memory, Short-Term - physiology ; Metabolic Diseases ; Middle Aged ; Neuropsychological Tests ; Pleiotropy ; Short term memory ; Young Adult</subject><ispartof>Diabetologia, 2020-05, Vol.63 (5), p.977-986</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-e461153c8356fc985f7c4ed153645df46f55556155699c601d73f6cbf8c701b53</citedby><cites>FETCH-LOGICAL-c474t-e461153c8356fc985f7c4ed153645df46f55556155699c601d73f6cbf8c701b53</cites><orcidid>0000-0003-4557-1838</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-020-05101-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-020-05101-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32016567$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mollon, Josephine</creatorcontrib><creatorcontrib>Curran, Joanne E.</creatorcontrib><creatorcontrib>Mathias, Samuel R.</creatorcontrib><creatorcontrib>Knowles, Emma E. M.</creatorcontrib><creatorcontrib>Carlisle, Phoebe</creatorcontrib><creatorcontrib>Fox, Peter T.</creatorcontrib><creatorcontrib>Olvera, Rene L.</creatorcontrib><creatorcontrib>Göring, Harald H. H.</creatorcontrib><creatorcontrib>Rodrigue, Amanda</creatorcontrib><creatorcontrib>Almasy, Laura</creatorcontrib><creatorcontrib>Duggirala, Ravi</creatorcontrib><creatorcontrib>Blangero, John</creatorcontrib><creatorcontrib>Glahn, David C.</creatorcontrib><title>Neurocognitive impairment in type 2 diabetes: evidence for shared genetic aetiology</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
Type 2 diabetes is associated with cognitive impairments, but it is unclear whether common genetic factors influence both type 2 diabetes risk and cognition.
Methods
Using data from 1892 Mexican-American individuals from extended pedigrees, including 402 with type 2 diabetes, we examined possible pleiotropy between type 2 diabetes and cognitive functioning, as measured by a comprehensive neuropsychological test battery.
Results
Negative phenotypic correlations (
ρ
p
) were observed between type 2 diabetes and measures of attention (Continuous Performance Test [CPT d′]:
ρ
p
= −0.143,
p
= 0.001), verbal memory (California Verbal Learning Test [CVLT] recall:
ρ
p
= −0.111,
p
= 0.004) and face memory (Penn Face Memory Test [PFMT]:
ρ
p
= −0.127,
p
= 0.002; PFMT Delayed:
ρ
p
=
−0.148,
p
= 2 × 10
−
4
), replicating findings of cognitive impairment in type 2 diabetes. Negative genetic correlations (
ρ
g
) were also observed between type 2 diabetes and measures of attention (CPT d′:
ρ
g
= −0.401,
p
= 0.001), working memory (digit span backward test:
ρ
g
= −0.380,
p
= 0.005), and face memory (PFMT:
ρ
g
= −0.476,
p
= 2 × 10
−
4
; PFMT Delayed:
ρ
g
= −0.376,
p
= 0.005), suggesting that the same genetic factors underlying risk for type 2 diabetes also influence poor cognitive performance in these domains. Performance in these domains was also associated with type 2 diabetes risk using an endophenotype ranking value approach. Specifically, on measures of attention (CPT d′:
β
= −0.219,
p
= 0.005), working memory (digit span backward:
β
= −0.326,
p
= 0.035), and face memory (PFMT:
β
= −0.171,
p
= 0.023; PFMT Delayed:
β
= −0.215,
p
= 0.005), individuals with type 2 diabetes showed the lowest performance, while unaffected/unrelated individuals showed the highest performance, and those related to an individual with type 2 diabetes performed at an intermediate level.
Conclusions/interpretation
These findings suggest that cognitive impairment may be a useful endophenotype of type 2 diabetes and, therefore, help to elucidate the pathophysiological underpinnings of this chronic disease.
Data availability
The data analysed in this study is available in dbGaP:
www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001215.v2.p2
.</description><subject>Adult</subject><subject>Chronic illnesses</subject><subject>Cognition</subject><subject>Cognition - physiology</subject><subject>Cognition Disorders - genetics</subject><subject>Cognition Disorders - physiopathology</subject><subject>Cognitive ability</subject><subject>Cognitive Dysfunction - genetics</subject><subject>Cognitive Dysfunction - physiopathology</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Face</subject><subject>Female</subject><subject>Genetic factors</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Memory</subject><subject>Memory, Short-Term - physiology</subject><subject>Metabolic Diseases</subject><subject>Middle Aged</subject><subject>Neuropsychological Tests</subject><subject>Pleiotropy</subject><subject>Short term memory</subject><subject>Young Adult</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU1v1DAQhi0EotvCH-CALHHhEhjHXwkHJFRBqVS1B0DiZnmdceoqiRc7WSn_HpctpXDAkj2S55nXM34JecHgDQPQbzMAq2UFNVQgGbBqfUQ2TPC6AlE3j8nmNl-xRn0_Isc53wAAl0I9JUe8Bqak0hvy5RKXFF3spzCHPdIw7mxII04zDROd1x3SmnbBbnHG_I7iPnQ4OaQ-JpqvbcKO9jjhHBy15YxD7Ndn5Im3Q8bnd_GEfPv08evp5-ri6uz89MNF5YQWc4VCMSa5a7hU3rWN9NoJ7MqVErLzQnlZlmJlt61TwDrNvXJb3zgNbCv5CXl_0N0t2xE7V5pOdjC7FEabVhNtMH9npnBt-rg3mklQEorA6zuBFH8smGczhuxwGOyEccmm5hLa8octL-irf9CbuKSpjFeoRpcuQbeFqg-USzHnhP6-GQbm1jNz8MwUz8wvz8xail4-HOO-5LdJBeAHIJfU1GP68_Z_ZH8CQgGieA</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Mollon, Josephine</creator><creator>Curran, Joanne E.</creator><creator>Mathias, Samuel R.</creator><creator>Knowles, Emma E. M.</creator><creator>Carlisle, Phoebe</creator><creator>Fox, Peter T.</creator><creator>Olvera, Rene L.</creator><creator>Göring, Harald H. H.</creator><creator>Rodrigue, Amanda</creator><creator>Almasy, Laura</creator><creator>Duggirala, Ravi</creator><creator>Blangero, John</creator><creator>Glahn, David C.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4557-1838</orcidid></search><sort><creationdate>20200501</creationdate><title>Neurocognitive impairment in type 2 diabetes: evidence for shared genetic aetiology</title><author>Mollon, Josephine ; Curran, Joanne E. ; Mathias, Samuel R. ; Knowles, Emma E. M. ; Carlisle, Phoebe ; Fox, Peter T. ; Olvera, Rene L. ; Göring, Harald H. H. ; Rodrigue, Amanda ; Almasy, Laura ; Duggirala, Ravi ; Blangero, John ; Glahn, David C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-e461153c8356fc985f7c4ed153645df46f55556155699c601d73f6cbf8c701b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Chronic illnesses</topic><topic>Cognition</topic><topic>Cognition - physiology</topic><topic>Cognition Disorders - genetics</topic><topic>Cognition Disorders - physiopathology</topic><topic>Cognitive ability</topic><topic>Cognitive Dysfunction - genetics</topic><topic>Cognitive Dysfunction - physiopathology</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Face</topic><topic>Female</topic><topic>Genetic factors</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Memory</topic><topic>Memory, Short-Term - physiology</topic><topic>Metabolic Diseases</topic><topic>Middle Aged</topic><topic>Neuropsychological Tests</topic><topic>Pleiotropy</topic><topic>Short term memory</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mollon, Josephine</creatorcontrib><creatorcontrib>Curran, Joanne E.</creatorcontrib><creatorcontrib>Mathias, Samuel R.</creatorcontrib><creatorcontrib>Knowles, Emma E. M.</creatorcontrib><creatorcontrib>Carlisle, Phoebe</creatorcontrib><creatorcontrib>Fox, Peter T.</creatorcontrib><creatorcontrib>Olvera, Rene L.</creatorcontrib><creatorcontrib>Göring, Harald H. H.</creatorcontrib><creatorcontrib>Rodrigue, Amanda</creatorcontrib><creatorcontrib>Almasy, Laura</creatorcontrib><creatorcontrib>Duggirala, Ravi</creatorcontrib><creatorcontrib>Blangero, John</creatorcontrib><creatorcontrib>Glahn, David C.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mollon, Josephine</au><au>Curran, Joanne E.</au><au>Mathias, Samuel R.</au><au>Knowles, Emma E. M.</au><au>Carlisle, Phoebe</au><au>Fox, Peter T.</au><au>Olvera, Rene L.</au><au>Göring, Harald H. H.</au><au>Rodrigue, Amanda</au><au>Almasy, Laura</au><au>Duggirala, Ravi</au><au>Blangero, John</au><au>Glahn, David C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neurocognitive impairment in type 2 diabetes: evidence for shared genetic aetiology</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>63</volume><issue>5</issue><spage>977</spage><epage>986</epage><pages>977-986</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
Type 2 diabetes is associated with cognitive impairments, but it is unclear whether common genetic factors influence both type 2 diabetes risk and cognition.
Methods
Using data from 1892 Mexican-American individuals from extended pedigrees, including 402 with type 2 diabetes, we examined possible pleiotropy between type 2 diabetes and cognitive functioning, as measured by a comprehensive neuropsychological test battery.
Results
Negative phenotypic correlations (
ρ
p
) were observed between type 2 diabetes and measures of attention (Continuous Performance Test [CPT d′]:
ρ
p
= −0.143,
p
= 0.001), verbal memory (California Verbal Learning Test [CVLT] recall:
ρ
p
= −0.111,
p
= 0.004) and face memory (Penn Face Memory Test [PFMT]:
ρ
p
= −0.127,
p
= 0.002; PFMT Delayed:
ρ
p
=
−0.148,
p
= 2 × 10
−
4
), replicating findings of cognitive impairment in type 2 diabetes. Negative genetic correlations (
ρ
g
) were also observed between type 2 diabetes and measures of attention (CPT d′:
ρ
g
= −0.401,
p
= 0.001), working memory (digit span backward test:
ρ
g
= −0.380,
p
= 0.005), and face memory (PFMT:
ρ
g
= −0.476,
p
= 2 × 10
−
4
; PFMT Delayed:
ρ
g
= −0.376,
p
= 0.005), suggesting that the same genetic factors underlying risk for type 2 diabetes also influence poor cognitive performance in these domains. Performance in these domains was also associated with type 2 diabetes risk using an endophenotype ranking value approach. Specifically, on measures of attention (CPT d′:
β
= −0.219,
p
= 0.005), working memory (digit span backward:
β
= −0.326,
p
= 0.035), and face memory (PFMT:
β
= −0.171,
p
= 0.023; PFMT Delayed:
β
= −0.215,
p
= 0.005), individuals with type 2 diabetes showed the lowest performance, while unaffected/unrelated individuals showed the highest performance, and those related to an individual with type 2 diabetes performed at an intermediate level.
Conclusions/interpretation
These findings suggest that cognitive impairment may be a useful endophenotype of type 2 diabetes and, therefore, help to elucidate the pathophysiological underpinnings of this chronic disease.
Data availability
The data analysed in this study is available in dbGaP:
www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001215.v2.p2
.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32016567</pmid><doi>10.1007/s00125-020-05101-y</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-4557-1838</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-186X |
| ispartof | Diabetologia, 2020-05, Vol.63 (5), p.977-986 |
| issn | 0012-186X 1432-0428 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7150650 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Adult Chronic illnesses Cognition Cognition - physiology Cognition Disorders - genetics Cognition Disorders - physiopathology Cognitive ability Cognitive Dysfunction - genetics Cognitive Dysfunction - physiopathology Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - physiopathology Face Female Genetic factors Human Physiology Humans Internal Medicine Male Medicine Medicine & Public Health Memory Memory, Short-Term - physiology Metabolic Diseases Middle Aged Neuropsychological Tests Pleiotropy Short term memory Young Adult |
| title | Neurocognitive impairment in type 2 diabetes: evidence for shared genetic aetiology |
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