Increased Genetic Risk for ADHD Potentiates Cognitive Impairment and Brain Hypometabolism in Alzheimer’s Disease Patients
Background Recent epidemiological studies showed that patients with attention‐deficit/hyperactivity disorder (ADHD) are more likely to be diagnosed with Alzheimer’s Disease (AD). Additionally, increased genetic risk for ADHD, measured with ADHD polygenic risk scores (ADHD‐PRS), was associated with a...
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| Veröffentlicht in: | Alzheimer's & dementia 2023-12, Vol.19 (S18), p.n/a |
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| creator | Leffa, Douglas Teixeira Povala, Guilherme Bellaver, Bruna Lussier, Firoza Z Ferrari‐Souza, João Pedro Ferreira, Pamela C.L. Zalzale, Hussein Aguzzoli, Cristiano Schaffer Rohden, Francieli Soares, Carolina Abbas, Sarah Tissot, Cécile Therriault, Joseph Lopez, Oscar L. Villemagne, Victor L Klunk, William E Cohen, Annie Zimmer, Eduardo R. Karikari, Thomas K Rosa‐Neto, Pedro Rohde, Luis Augusto Molina, Brooke Pascoal, Tharick Ali |
| description | Background
Recent epidemiological studies showed that patients with attention‐deficit/hyperactivity disorder (ADHD) are more likely to be diagnosed with Alzheimer’s Disease (AD). Additionally, increased genetic risk for ADHD, measured with ADHD polygenic risk scores (ADHD‐PRS), was associated with amyloid‐dependent cognitive decline in older adults. However, it is unclear whether higher genetic risk for ADHD is associated with worse cognitive function in patients with AD dementia.
Method
We used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to investigate the association between cognitive function (Preclinical Alzheimer Cognitive Composite [PACC], executive function, and memory) and ADHD‐PRS in subjects with AD dementia. Additionally, we tested whether ADHD‐PRS potentiated brain hypometabolism measured with [18F]FDG‐PET. Analyses were controlled by age, sex, years of study, and number of APOE ε4 alleles.
Result
We evaluated baseline data from 264 AD patients (114 women [43.2%], mean [SD] age of 75 [7.6] years). ADHD‐PRS was associated with decreased cognitive function (p‐value = .04, η2 = .01, Figure 1a), more specifically in executive function (p‐value = .04, η2 = .01, Figure 1c). Higher ADHD‐PRS was associated with brain hypometabolism in frontal, parietal, and temporal regions (Figure 2a,b). Brain hypometabolism correlated with worse cognitive function in the following regions: postcentral gyrus (p‐value = .01, η2 = .03), superior parietal gyrus (p‐value = .001, η2 = .07), precentral gyrus (p‐value = .004, η2 = .05), and fusiform gyrus (p‐value |
| doi_str_mv | 10.1002/alz.080519 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1002_alz_080519</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>ALZ080519</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1139-250df5cc8aabcb04cb635d58c5fa43e7a2c313626163a9c5f04e42a7f421e6c53</originalsourceid><addsrcrecordid>eNp9kM1Kw0AUhQdRsFY3PsGshdT5yaTJMrbaFgoW0Y2bcDO50dH8lJnBkrrxNXw9n8SUFpeu7uXc79wDh5BLzkacMXEN1XbEYqZ4ckQGXCkRKDFOjv_2iJ2SM-feGAtZzNWAfC4abREcFnSGDXqj6YNx77RsLU2n8yldtR4bb8Cjo5P2pTHefCBd1Gswtu4vFJqC3lgwDZ1367ZGD3lbGVfTXkmr7SuaGu3P17ejU-N2SXQF3vROd05OSqgcXhzmkDzd3T5O5sHyfraYpMtAcy6TQChWlErrGCDXOQt1HklVqFirEkKJYxBachmJiEcSkl5lIYYCxmUoOEZaySG52v_VtnXOYpmtranBdhln2a62rK8t29fWw3wPb0yF3T9kli6fD55fd49yJQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Increased Genetic Risk for ADHD Potentiates Cognitive Impairment and Brain Hypometabolism in Alzheimer’s Disease Patients</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Leffa, Douglas Teixeira ; Povala, Guilherme ; Bellaver, Bruna ; Lussier, Firoza Z ; Ferrari‐Souza, João Pedro ; Ferreira, Pamela C.L. ; Zalzale, Hussein ; Aguzzoli, Cristiano Schaffer ; Rohden, Francieli ; Soares, Carolina ; Abbas, Sarah ; Tissot, Cécile ; Therriault, Joseph ; Lopez, Oscar L. ; Villemagne, Victor L ; Klunk, William E ; Cohen, Annie ; Zimmer, Eduardo R. ; Karikari, Thomas K ; Rosa‐Neto, Pedro ; Rohde, Luis Augusto ; Molina, Brooke ; Pascoal, Tharick Ali</creator><creatorcontrib>Leffa, Douglas Teixeira ; Povala, Guilherme ; Bellaver, Bruna ; Lussier, Firoza Z ; Ferrari‐Souza, João Pedro ; Ferreira, Pamela C.L. ; Zalzale, Hussein ; Aguzzoli, Cristiano Schaffer ; Rohden, Francieli ; Soares, Carolina ; Abbas, Sarah ; Tissot, Cécile ; Therriault, Joseph ; Lopez, Oscar L. ; Villemagne, Victor L ; Klunk, William E ; Cohen, Annie ; Zimmer, Eduardo R. ; Karikari, Thomas K ; Rosa‐Neto, Pedro ; Rohde, Luis Augusto ; Molina, Brooke ; Pascoal, Tharick Ali</creatorcontrib><description>Background
Recent epidemiological studies showed that patients with attention‐deficit/hyperactivity disorder (ADHD) are more likely to be diagnosed with Alzheimer’s Disease (AD). Additionally, increased genetic risk for ADHD, measured with ADHD polygenic risk scores (ADHD‐PRS), was associated with amyloid‐dependent cognitive decline in older adults. However, it is unclear whether higher genetic risk for ADHD is associated with worse cognitive function in patients with AD dementia.
Method
We used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to investigate the association between cognitive function (Preclinical Alzheimer Cognitive Composite [PACC], executive function, and memory) and ADHD‐PRS in subjects with AD dementia. Additionally, we tested whether ADHD‐PRS potentiated brain hypometabolism measured with [18F]FDG‐PET. Analyses were controlled by age, sex, years of study, and number of APOE ε4 alleles.
Result
We evaluated baseline data from 264 AD patients (114 women [43.2%], mean [SD] age of 75 [7.6] years). ADHD‐PRS was associated with decreased cognitive function (p‐value = .04, η2 = .01, Figure 1a), more specifically in executive function (p‐value = .04, η2 = .01, Figure 1c). Higher ADHD‐PRS was associated with brain hypometabolism in frontal, parietal, and temporal regions (Figure 2a,b). Brain hypometabolism correlated with worse cognitive function in the following regions: postcentral gyrus (p‐value = .01, η2 = .03), superior parietal gyrus (p‐value = .001, η2 = .07), precentral gyrus (p‐value = .004, η2 = .05), and fusiform gyrus (p‐value<.0001, η2 = .08, Figure 2c,d,e,f). Finally, decreased metabolism in these four regions mediated the effect of ADHD‐PRS on cognitive function (Figure 3).
Conclusion
Findings indicate that a higher genetic risk for ADHD is correlated with impaired cognitive function with small effect sizes. Moreover, the effects of the genetic risk of ADHD on cognitive function were mediated by hypometabolism in frontal, parietal, and temporal brain regions, which could point to a decrease resilience to AD pathology in individuals with ADHD. Clinically, our findings suggest that patients with comorbid ADHD and AD dementia have a more severe disease phenotype, with potential implications for prognosis and treatment.</description><identifier>ISSN: 1552-5260</identifier><identifier>EISSN: 1552-5279</identifier><identifier>DOI: 10.1002/alz.080519</identifier><language>eng</language><ispartof>Alzheimer's & dementia, 2023-12, Vol.19 (S18), p.n/a</ispartof><rights>2023 the Alzheimer's Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Falz.080519$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Falz.080519$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Leffa, Douglas Teixeira</creatorcontrib><creatorcontrib>Povala, Guilherme</creatorcontrib><creatorcontrib>Bellaver, Bruna</creatorcontrib><creatorcontrib>Lussier, Firoza Z</creatorcontrib><creatorcontrib>Ferrari‐Souza, João Pedro</creatorcontrib><creatorcontrib>Ferreira, Pamela C.L.</creatorcontrib><creatorcontrib>Zalzale, Hussein</creatorcontrib><creatorcontrib>Aguzzoli, Cristiano Schaffer</creatorcontrib><creatorcontrib>Rohden, Francieli</creatorcontrib><creatorcontrib>Soares, Carolina</creatorcontrib><creatorcontrib>Abbas, Sarah</creatorcontrib><creatorcontrib>Tissot, Cécile</creatorcontrib><creatorcontrib>Therriault, Joseph</creatorcontrib><creatorcontrib>Lopez, Oscar L.</creatorcontrib><creatorcontrib>Villemagne, Victor L</creatorcontrib><creatorcontrib>Klunk, William E</creatorcontrib><creatorcontrib>Cohen, Annie</creatorcontrib><creatorcontrib>Zimmer, Eduardo R.</creatorcontrib><creatorcontrib>Karikari, Thomas K</creatorcontrib><creatorcontrib>Rosa‐Neto, Pedro</creatorcontrib><creatorcontrib>Rohde, Luis Augusto</creatorcontrib><creatorcontrib>Molina, Brooke</creatorcontrib><creatorcontrib>Pascoal, Tharick Ali</creatorcontrib><title>Increased Genetic Risk for ADHD Potentiates Cognitive Impairment and Brain Hypometabolism in Alzheimer’s Disease Patients</title><title>Alzheimer's & dementia</title><description>Background
Recent epidemiological studies showed that patients with attention‐deficit/hyperactivity disorder (ADHD) are more likely to be diagnosed with Alzheimer’s Disease (AD). Additionally, increased genetic risk for ADHD, measured with ADHD polygenic risk scores (ADHD‐PRS), was associated with amyloid‐dependent cognitive decline in older adults. However, it is unclear whether higher genetic risk for ADHD is associated with worse cognitive function in patients with AD dementia.
Method
We used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to investigate the association between cognitive function (Preclinical Alzheimer Cognitive Composite [PACC], executive function, and memory) and ADHD‐PRS in subjects with AD dementia. Additionally, we tested whether ADHD‐PRS potentiated brain hypometabolism measured with [18F]FDG‐PET. Analyses were controlled by age, sex, years of study, and number of APOE ε4 alleles.
Result
We evaluated baseline data from 264 AD patients (114 women [43.2%], mean [SD] age of 75 [7.6] years). ADHD‐PRS was associated with decreased cognitive function (p‐value = .04, η2 = .01, Figure 1a), more specifically in executive function (p‐value = .04, η2 = .01, Figure 1c). Higher ADHD‐PRS was associated with brain hypometabolism in frontal, parietal, and temporal regions (Figure 2a,b). Brain hypometabolism correlated with worse cognitive function in the following regions: postcentral gyrus (p‐value = .01, η2 = .03), superior parietal gyrus (p‐value = .001, η2 = .07), precentral gyrus (p‐value = .004, η2 = .05), and fusiform gyrus (p‐value<.0001, η2 = .08, Figure 2c,d,e,f). Finally, decreased metabolism in these four regions mediated the effect of ADHD‐PRS on cognitive function (Figure 3).
Conclusion
Findings indicate that a higher genetic risk for ADHD is correlated with impaired cognitive function with small effect sizes. Moreover, the effects of the genetic risk of ADHD on cognitive function were mediated by hypometabolism in frontal, parietal, and temporal brain regions, which could point to a decrease resilience to AD pathology in individuals with ADHD. Clinically, our findings suggest that patients with comorbid ADHD and AD dementia have a more severe disease phenotype, with potential implications for prognosis and treatment.</description><issn>1552-5260</issn><issn>1552-5279</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kM1Kw0AUhQdRsFY3PsGshdT5yaTJMrbaFgoW0Y2bcDO50dH8lJnBkrrxNXw9n8SUFpeu7uXc79wDh5BLzkacMXEN1XbEYqZ4ckQGXCkRKDFOjv_2iJ2SM-feGAtZzNWAfC4abREcFnSGDXqj6YNx77RsLU2n8yldtR4bb8Cjo5P2pTHefCBd1Gswtu4vFJqC3lgwDZ1367ZGD3lbGVfTXkmr7SuaGu3P17ejU-N2SXQF3vROd05OSqgcXhzmkDzd3T5O5sHyfraYpMtAcy6TQChWlErrGCDXOQt1HklVqFirEkKJYxBachmJiEcSkl5lIYYCxmUoOEZaySG52v_VtnXOYpmtranBdhln2a62rK8t29fWw3wPb0yF3T9kli6fD55fd49yJQ</recordid><startdate>202312</startdate><enddate>202312</enddate><creator>Leffa, Douglas Teixeira</creator><creator>Povala, Guilherme</creator><creator>Bellaver, Bruna</creator><creator>Lussier, Firoza Z</creator><creator>Ferrari‐Souza, João Pedro</creator><creator>Ferreira, Pamela C.L.</creator><creator>Zalzale, Hussein</creator><creator>Aguzzoli, Cristiano Schaffer</creator><creator>Rohden, Francieli</creator><creator>Soares, Carolina</creator><creator>Abbas, Sarah</creator><creator>Tissot, Cécile</creator><creator>Therriault, Joseph</creator><creator>Lopez, Oscar L.</creator><creator>Villemagne, Victor L</creator><creator>Klunk, William E</creator><creator>Cohen, Annie</creator><creator>Zimmer, Eduardo R.</creator><creator>Karikari, Thomas K</creator><creator>Rosa‐Neto, Pedro</creator><creator>Rohde, Luis Augusto</creator><creator>Molina, Brooke</creator><creator>Pascoal, Tharick Ali</creator><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>202312</creationdate><title>Increased Genetic Risk for ADHD Potentiates Cognitive Impairment and Brain Hypometabolism in Alzheimer’s Disease Patients</title><author>Leffa, Douglas Teixeira ; Povala, Guilherme ; Bellaver, Bruna ; Lussier, Firoza Z ; Ferrari‐Souza, João Pedro ; Ferreira, Pamela C.L. ; Zalzale, Hussein ; Aguzzoli, Cristiano Schaffer ; Rohden, Francieli ; Soares, Carolina ; Abbas, Sarah ; Tissot, Cécile ; Therriault, Joseph ; Lopez, Oscar L. ; Villemagne, Victor L ; Klunk, William E ; Cohen, Annie ; Zimmer, Eduardo R. ; Karikari, Thomas K ; Rosa‐Neto, Pedro ; Rohde, Luis Augusto ; Molina, Brooke ; Pascoal, Tharick Ali</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1139-250df5cc8aabcb04cb635d58c5fa43e7a2c313626163a9c5f04e42a7f421e6c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leffa, Douglas Teixeira</creatorcontrib><creatorcontrib>Povala, Guilherme</creatorcontrib><creatorcontrib>Bellaver, Bruna</creatorcontrib><creatorcontrib>Lussier, Firoza Z</creatorcontrib><creatorcontrib>Ferrari‐Souza, João Pedro</creatorcontrib><creatorcontrib>Ferreira, Pamela C.L.</creatorcontrib><creatorcontrib>Zalzale, Hussein</creatorcontrib><creatorcontrib>Aguzzoli, Cristiano Schaffer</creatorcontrib><creatorcontrib>Rohden, Francieli</creatorcontrib><creatorcontrib>Soares, Carolina</creatorcontrib><creatorcontrib>Abbas, Sarah</creatorcontrib><creatorcontrib>Tissot, Cécile</creatorcontrib><creatorcontrib>Therriault, Joseph</creatorcontrib><creatorcontrib>Lopez, Oscar L.</creatorcontrib><creatorcontrib>Villemagne, Victor L</creatorcontrib><creatorcontrib>Klunk, William E</creatorcontrib><creatorcontrib>Cohen, Annie</creatorcontrib><creatorcontrib>Zimmer, Eduardo R.</creatorcontrib><creatorcontrib>Karikari, Thomas K</creatorcontrib><creatorcontrib>Rosa‐Neto, Pedro</creatorcontrib><creatorcontrib>Rohde, Luis Augusto</creatorcontrib><creatorcontrib>Molina, Brooke</creatorcontrib><creatorcontrib>Pascoal, Tharick Ali</creatorcontrib><collection>CrossRef</collection><jtitle>Alzheimer's & dementia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leffa, Douglas Teixeira</au><au>Povala, Guilherme</au><au>Bellaver, Bruna</au><au>Lussier, Firoza Z</au><au>Ferrari‐Souza, João Pedro</au><au>Ferreira, Pamela C.L.</au><au>Zalzale, Hussein</au><au>Aguzzoli, Cristiano Schaffer</au><au>Rohden, Francieli</au><au>Soares, Carolina</au><au>Abbas, Sarah</au><au>Tissot, Cécile</au><au>Therriault, Joseph</au><au>Lopez, Oscar L.</au><au>Villemagne, Victor L</au><au>Klunk, William E</au><au>Cohen, Annie</au><au>Zimmer, Eduardo R.</au><au>Karikari, Thomas K</au><au>Rosa‐Neto, Pedro</au><au>Rohde, Luis Augusto</au><au>Molina, Brooke</au><au>Pascoal, Tharick Ali</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Genetic Risk for ADHD Potentiates Cognitive Impairment and Brain Hypometabolism in Alzheimer’s Disease Patients</atitle><jtitle>Alzheimer's & dementia</jtitle><date>2023-12</date><risdate>2023</risdate><volume>19</volume><issue>S18</issue><epage>n/a</epage><issn>1552-5260</issn><eissn>1552-5279</eissn><abstract>Background
Recent epidemiological studies showed that patients with attention‐deficit/hyperactivity disorder (ADHD) are more likely to be diagnosed with Alzheimer’s Disease (AD). Additionally, increased genetic risk for ADHD, measured with ADHD polygenic risk scores (ADHD‐PRS), was associated with amyloid‐dependent cognitive decline in older adults. However, it is unclear whether higher genetic risk for ADHD is associated with worse cognitive function in patients with AD dementia.
Method
We used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to investigate the association between cognitive function (Preclinical Alzheimer Cognitive Composite [PACC], executive function, and memory) and ADHD‐PRS in subjects with AD dementia. Additionally, we tested whether ADHD‐PRS potentiated brain hypometabolism measured with [18F]FDG‐PET. Analyses were controlled by age, sex, years of study, and number of APOE ε4 alleles.
Result
We evaluated baseline data from 264 AD patients (114 women [43.2%], mean [SD] age of 75 [7.6] years). ADHD‐PRS was associated with decreased cognitive function (p‐value = .04, η2 = .01, Figure 1a), more specifically in executive function (p‐value = .04, η2 = .01, Figure 1c). Higher ADHD‐PRS was associated with brain hypometabolism in frontal, parietal, and temporal regions (Figure 2a,b). Brain hypometabolism correlated with worse cognitive function in the following regions: postcentral gyrus (p‐value = .01, η2 = .03), superior parietal gyrus (p‐value = .001, η2 = .07), precentral gyrus (p‐value = .004, η2 = .05), and fusiform gyrus (p‐value<.0001, η2 = .08, Figure 2c,d,e,f). Finally, decreased metabolism in these four regions mediated the effect of ADHD‐PRS on cognitive function (Figure 3).
Conclusion
Findings indicate that a higher genetic risk for ADHD is correlated with impaired cognitive function with small effect sizes. Moreover, the effects of the genetic risk of ADHD on cognitive function were mediated by hypometabolism in frontal, parietal, and temporal brain regions, which could point to a decrease resilience to AD pathology in individuals with ADHD. Clinically, our findings suggest that patients with comorbid ADHD and AD dementia have a more severe disease phenotype, with potential implications for prognosis and treatment.</abstract><doi>10.1002/alz.080519</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| title | Increased Genetic Risk for ADHD Potentiates Cognitive Impairment and Brain Hypometabolism in Alzheimer’s Disease Patients |
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