Genetic risk of attention-deficit/hyperactivity disorder predicts cognitive decline and development of Alzheimer’s disease pathophysiology in older adults without cognitive impairment – Molecular Psychiatry

Faraone SV, Banaschewski T, Coghill D, Zheng Y, Biederman J, Bellgrove MA, et al. ADHD World Federation International Consensus Statement: 208 evidence-based conclusions about the disorder. Neurosci Biobehav Rev. 2021 https://www.sciencedirect.com/science/article/pii/S014976342100049X

Caye A, Spadini AV, Karam RG, Grevet EH, Rovaris DL, Bau CHD, et al. Predictors of persistence of ADHD in adulthood: systematic review of the literature and meta-analysis. Eur child psychiatry of adolescence. 2016;25:1151–9.

PubMed Google Scholar article

Kooij JJS, Michielsen M, Kruithof H, Bijlenga D. ADHD in the elderly: literature review and proposal for assessment and treatment. Expert Rev Neurother. 2016;16:1371–81.

CAS PubMed Google Scholar Article

Dobrosavljevic M, Solares C, Cortese S, Andershed H, Larsson H. Prevalence of attention deficit/hyperactivity disorder in older adults: systematic review and meta-analysis. Neurosci Biobehav Rev. 2020;118:282–9. https://doi.org/10.1016/j.neubiorev.2020.07.042.

PubMed Google Scholar article

Callahan BL, Bierstone D, Stuss DT, Black SE. Adult ADHD: risk factor for dementia or phenotypic mimicry? Front Aging Neurosci. 2017;9:1–15.

Google Scholar article

Du Rietz E, Brikell I, Butwicka A, Leone M, Chang Z, Cortese S, et al. Mapping phenotypic and etiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed registry study. Lancet Psychiatry. 2021;8:774–83. Available at: https://doi.org/10.1016/S2215-0366(21)00171-1

Zhang L, Du Rietz E, Kuja-Halkola R, Dobrosavljevic M, Johnell K, Pedersen NL, et al. Attention deficit/hyperactivity disorder and Alzheimer’s disease and all forms of dementia: a multi-generational cohort study in Sweden. Alzheimer’s dementia. 2020; 2021: 1–9.

Google Scholar

Dobrosavljevic M, Zhang L, Garcia-Argibay M, Du Rietz E, Andershed H, Chang Z, et al. Attention deficit/hyperactivity disorder as a risk factor for dementia and mild cognitive impairment: a population-based registry study. Eur Psychiatry. 2022;65:e3. https://www.cambridge.org/core/article/attentiondeficithyperactivity-disorder-as-a-risk-factor-for-dementia-and-mild-cognitive-impairment-a-populationbased-register-study/E289DAD7BE1BFB781389CF369EF7ECB3

Google Scholar article

Becker S, Sharma MJ, Callahan BL. ADHD and risk of neurodegenerative diseases: critical review of the evidence. Front Aging Neurosci. 2022;13.

Ronald A, de Bode N, Polderman TJC. Systematic review: how the polygenic risk score for attention deficit/hyperactivity disorder contributes to our understanding of ADHD and related traits. J Am Acad adolescent child psychiatry. 2021;60:1234–77.

Thapar A. ADHD Genetics Discoveries in the 21st Century: New Findings and Their Implications. Am J Psychiatry. 2018;175:943–50.

PubMed Google Scholar article

Petersen RC, Aisen PS, Beckett LA, Donohue MC, Gamst AC, Harvey DJ, et al. Alzheimer’s Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology. 2010;74:201–9.

PubMed Article PubMed Central Google Scholar

Zettergren A, Lord J, Ashton NJ, Benedet AL, Karikari TK, Lantero Rodriguez J, et al. Association between polygenic risk score for Alzheimer’s disease and plasma phosphorylated tau protein in Alzheimer’s Disease Neuroimaging Initiative individuals. Alzheimer Res Ther. 2021;13:17. https://doi.org/10.1186/s13195-020-00754-8.

CAS PubMed Article PubMed Central Google Scholar

Demontis D, Walters RK, Martin J, Mattheisen M, Als TD, Agerbo E, et al. Discovery of the first significant genome-wide risk loci for attention-deficit/hyperactivity disorder. Nat Genet. 2019;51:63–75.

CAS PubMed Google Scholar Article

Euesden J, Lewis CM, O’Reilly PF. PRSice: Polygenic risk scoring software. Bioinformatics. 2015;31:1466–8.

CAS PubMed Google Scholar Article

Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ. Second Generation PLINK: Meeting the Challenge of Larger and Richer Datasets. Gigascience. 2015;4:7.

PubMed Article PubMed Central Google Scholar

Donohue MC, Sperling RA, Salmon DP, Rentz DM, Raman R, Thomas RG, et al. The preclinical Alzheimer’s cognitive composite: measuring amyloid-related decline. JAMA Neurol. 2014;71:961–70.

PubMed Article PubMed Central Google Scholar

Gibbons LE, Carle AC, Mackin RS, Harvey D, Mukherjee S, Insel P, et al. A composite score for executive functioning, validated in Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants with mild baseline cognitive impairment. Brain imaging behavior. 2012;6:517–27.

PubMed Article PubMed Central Google Scholar

Crane PK, Carle A, Gibbons LE, Insel P, Mackin RS, Gross A, et al. Development and evaluation of a composite score for memory in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Brain imaging behavior. 2012;6:502–16.

PubMed Article PubMed Central Google Scholar

Jack CRJ, Bernstein MA, Fox NC, Thompson P, Alexander G, Harvey D, et al. The Alzheimer’s Disease Neuroimaging Initiative (ADNI): MRI Methods. J Magn resonance imaging. 2008;27:685–91.

PubMed Article PubMed Central Google Scholar

Landau SM, Mintun MA, Joshi AD, Koeppe RA, Petersen RC, Aisen PS, et al. Amyloid deposition, hypometabolism and longitudinal cognitive decline. Anne Neurol. 2012;72:578–86.

CAS PubMed Article PubMed Central Google Scholar

Hansson O, Seibyl J, Stomrud E, Zetterberg H, Trojanowski JQ, Bittner T, et al. CSF biomarkers of Alzheimer’s disease are consistent with amyloid-β PET and predict clinical progression: a study of fully automated immunoassays in the BioFINDER and ADNI cohorts. Alzheimer’s dementia. 2018;14:1470–81.

PubMed Article PubMed Central Google Scholar

Mathotaarachchi S, Wang S, Shin M, Pascoal TA, Benedet AL, Kang MS, et al. VoxelStats: A MATLAB package for voxel-based multimodal brain image analysis. 10, Front Neuroinformatics. 2016. Available at: https://www.frontiersin.org/article/10.3389/fninf.2016.00020

Selya A, Rose J, Dierker L, Hedeker D, Mermelstein R. A practical guide to calculating Cohen’s f2, a measure of side-effect size, from PROC MIXED. Flight. 3, Front Psychol. 2012. Available at: https://www.frontiersin.org/article/10.3389/fpsyg.2012.00111

Keller MC. Gene × environment interaction studies have not adequately controlled for potential confounders: the problem and the (simple) solution. Biol Psychiatry. 2014;75:18–24.

PubMed Google Scholar article

Knopman DS, Amieva H, Petersen RC, Chételat G, Holtzman DM, Hyman BT, et al. Alzheimer’s disease. Nat Rev Dis Prim. 2021;7:33 https://doi.org/10.1038/s41572-021-00269-y. Available from

PubMed Google Scholar article

Ferrari-Souza JP, Brum WS, Hauschild LA, Da Ros LU, Lukasewicz Ferreira PC, Bellaver B, et al. The burden of vascular risk is a key player in the early progression of Alzheimer’s disease. medRxiv. 2021.12.18.21267994. http://medrxiv.org/content/early/2021/12/19/2021.12.18.21267994.abstract

Mendonca F, Sudo FK, Santiago-Bravo G, Oliveira N, Assuncao N, Rodrigues F, et al. Mild cognitive impairment or attention deficit/hyperactivity disorder in the elderly? A cross-sectional study. Frontal psychiatry. 2021;12:12–7.

Google Scholar article

Ossenkoppele R, Binette AP, Groot C, Smith R, Strandberg O, Palmqvist S, et al. Cognitive individuals positive for amyloid and Tau PET: destined to decline? medRxiv. 2022;2022.05.23.22275241. http://medrxiv.org/content/early/2022/05/25/2022.05.23.22275241.abstract

Donohue MC, Sperling RA, Petersen R, Sun CK, Weiner M, Aisen PS. Association between elevated brain amyloid and subsequent cognitive decline in cognitively normal people. JAMA – J Am Med Assoc. 2017;317:2305–16.

CAS Google Scholar Article

Strikwerda-Brown C, Hobbs DA, Gonneaud J, St-Onge F, Binette AP, Ozlen H, et al. Association of elevated amyloid and tau emission tomography signal with the short-term development of Alzheimer’s disease symptoms in older adults without cognitive impairment. JAMA Neurol. 2022;79:975–85. https://doi.org/10.1001/jamaneurol.2022.2379.

Jack CRJ, Wiste HJ, Therneau TM, Weigand SD, Knopman DS, Mielke MM, et al. Associations of amyloid, Tau, and neurodegeneration biomarker profiles with rates of memory decline in people without dementia. JAMA. 2019;321:2316–25.

CAS PubMed Article PubMed Central Google Scholar

Hanseeuw BJ, Betensky RA, Jacobs HIL, Schultz AP, Sepulcre J, Becker JA, et al. Association of amyloid and Tau with cognition in preclinical Alzheimer’s disease: a longitudinal study. JAMA Neurol. 2019;76:915–24. https://doi.org/10.1001/jamaneurol.2019.1424.

PubMed Article PubMed Central Google Scholar

Long JM, Holtzman DM. Alzheimer’s disease: An update on pathobiology and treatment strategies. Cell. 2019;179:312–39. https://doi.org/10.1016/j.cell.2019.09.001.

CAS PubMed Article PubMed Central Google Scholar

Jansen WJ, Janssen O, Tijms BM, Vos SJB, Ossenkoppele R, Visser PJ, et al. Estimates of the prevalence of amyloid abnormality in the clinical spectrum of Alzheimer’s disease. JAMA Neurol. 2022 https://doi.org/10.1001/jamaneurol.2021.5216

Joy R, Bejanin A, Fagan AM, Ayakta N, Baker SL, Bourakova V, et al. Associations between [(18)F]AV1451 tau PET and CSF measures tau pathology in a clinical specimen. Neurology. 2018;90:e282–90.

PubMed Article PubMed Central Google Scholar

Frisoni GB, Fox NC, Jack CR Jr, Scheltens P, Thompson PM. The clinical use of structural MRI in Alzheimer’s disease. Nat Rev Neurol. 2010;6:67–77. https://pubmed.ncbi.nlm.nih.gov/20139996

PubMed Article PubMed Central Google Scholar

Moreno-Alcázar A, Ramos-Quiroga JA, Radua J, Salavert J, Palomar G, Bosch R, et al. Brain abnormalities in adults with attention deficit hyperactivity disorder revealed by voxel-based morphometry. Psychiatry Res Neuroimaging. 2016;254:41–7. https://www.sciencedirect.com/science/article/pii/S0925492715301815

PubMed Google Scholar article

Klein M, Souza-Duran FL, Menezes AKPM, Alves TM, Busatto G, Louzã MR. Gray matter volume in older adults with ADHD: associations of symptoms and comorbidities with brain structures. J Atten Disord. 2021;25:829–38.

PubMed Google Scholar article

Fuermaier ABM, Tucha L, Koerts J, Aschenbrenner S, Weisbrod M, Lange KW, et al. Cognitive disorders in adults with attention deficit hyperactivity disorder. Clin Neuropsychol. 2014;28:1104–22.

PubMed Google Scholar article