Cognitive and Neuroimaging Profiles of Older Adults With Attention Deficit/Hyperactivity Disorder Presenting to a Memory Clinic

Brandy L Callahan, Nayani Ramakrishnan, Prathiba Shammi, Daniel Bierstone, Rebecca Taylor, Miracle Ozzoude, Maged Goubran, Donald T Stuss, Sandra E Black, Brandy L Callahan, Nayani Ramakrishnan, Prathiba Shammi, Daniel Bierstone, Rebecca Taylor, Miracle Ozzoude, Maged Goubran, Donald T Stuss, Sandra E Black

Abstract

Objective: Some features of attention-deficit/hyperactivity disorder (ADHD) may resemble those of mild cognitive impairment (MCI) in older adults, contributing to diagnostic uncertainty in individuals seeking assessment in memory clinics. We systematically compared cognition and brain structure in ADHD and MCI to clarify the extent of overlap and identify potential features unique to each.

Method: Older adults from a Cognitive Neurology clinic (40 ADHD, 29 MCI, 37 controls) underwent neuropsychological assessment. A subsample (n = 80) underwent structural neuroimaging.

Results: Memory was impaired in both patient groups, but reflected a storage deficit in MCI (supported by relatively smaller hippocampi) and an encoding deficit in ADHD (supported by frontal lobe thinning). Both groups displayed normal executive functioning. Semantic retrieval was uniquely impaired in MCI.

Conclusion: Although ADHD has been proposed as a dementia risk factor or prodrome, we propose it is rather a pathophysiologically-unique phenotypic mimic acting via overlap in memory and executive performance.

Trial registration: ClinicalTrials.gov NCT01800214.

Keywords: ADD; MRI; attention-deficit disorder; dementia; language; neuropsychology.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Flowchart illustrating ADHD classification.
Figure 2.
Figure 2.
Frontal-lobe (1) and whole-brain (2) cortical thickness analysis showing frontal regions with decreased cortical thickness in (A) ADHD relative to controls and (B) ADHD relative to MCI. Notes. ADHD = attention-deficit/hyperactivity disorder; LLOF = left lateral orbitofrontal; LP = left precentral; LPos = left postcentral; LSP = left superior parietal; MCI = mild cognitive impairment; RLO = right lateral occipital; RLOF = right lateral orbitofrontal; RP = right precentral; RPars = right pars opercularis; RRMF = right rostral middle frontal.

References

    1. Adler L., Shaw D., Sitt D., Maya E., Morrill M. I. (2009). Issues in the diagnosis and treatment of adult ADHD by primary care physicians. Primary Psychiatry, 16(5), 57–63.
    1. Aly M., Turk-Browne N. B. (2017). How hippocampal memory shapes, and is shaped by, attention. In Hannula D., Duff M. (Eds.), The hippocampus from cells to systems (pp. 369–403). Springer International Publishing.
    1. American Psychological Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5) (5th ed.). American Psychiatric Publishing.
    1. Asherson P., Buitelaar J., Faraone S. V., Rohde L. A. (2016). Adult attention-deficit hyperactivity disorder: Key conceptual issues. The Lancet Psychiatry, 3, 568–578. 10.1016/S2215-0366(16)30032-3
    1. Bakkour A., Morris J. C., Dickerson B. C. (2009). The cortical signature of prodromal AD: Regional thinning predicts mild AD dementia. Neurology, 72(12), 1048–1055. 10.1212/01.wnl.0000340981.97664.2f
    1. Barkley R. (2011. a). Barkley Adult ADHD rRating sScale-IV (BAARS-IV) (4th ed.). Guilford Press.
    1. Barkley R. (2011. b). Barkley deficits in executive functioning scale (BDEFS). Guilford Press.
    1. Barkley R. A. (2019). Neuropsychological testing is not useful in the diagnosis of ADHD: Stop it (or prove it)! The ADHD Report, 27(2), 1–8. 10.1521/adhd.2019.27.2.1
    1. Barkley R. A., Murphy K. R. (2010). Impairment in occupational functioning and adult ADHD: The predictive utility of executive function (EF) ratings versus EF tests. Archives of Clinical Neuropsychology: The Official Journal of the National Academy of Neuropsychologists, 25(3), 157–173. 10.1093/arclin/acq014
    1. Blackburn D. J., Wakefield S., Shanks M. F., Harkness K., Reuber M., Venneri A. (2014). Memory difficulties are not always a sign of incipient dementia: A review of the possible causes of loss of memory efficiency. British Medical Bulletin, 112(1), 71–81. 10.1093/bmb/ldu029
    1. Braak H., Braak E. (1995). Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiology of Aging, 16(3), 271–278. 10.1016/0197-4580(95)00021-6
    1. Bramham J., Murphy D. G., Xenitidis K., Asherson P., Hopkin G., Young S. (2012). Adults with attention deficit hyperactivity disorder: An investigation of age-related differences in behavioural symptoms, neuropsychological function and co-morbidity. Psychological Medicine, 42(10), 2225–2234. 10.1017/S0033291712000219
    1. Bueno V. F., da Silva M. A., Alves T. M., Louzã M. R., Pompéia S. (2017). Fractionating executive functions of adults with ADHD. Journal of Attention Disorders, 21, 944–955. 10.1177/1087054714545537
    1. Callahan B. L., Bierstone D., Stuss D. T., Black S. E. (2017). Adult ADHD: Risk factor for dementia or phenotypic mimic? Frontiers in Aging Neuroscience, 9, 260.
    1. Carr L. A., Nigg J. T., Henderson J. M. (2006). Attentional versus motor inhibition in adults with attention-deficit/hyperactivity disorder. Neuropsychology, 20(4), 430–441. 10.1037/0894-4105.20.4.430
    1. Conners C., Erhardt D., Sparrow E. (1999). CAARS adult ADHD rating scales. Technical manual. Multi-Health Systems.
    1. Curley L. B., Newman E., Thompson W. K., Brown T. T., Hagler D. J., Akshoomoff N., Reuter C., Dale A. M., Jernigan T. L. (2018). Cortical morphology of the pars opercularis and its relationship to motor-inhibitory performance in a longitudinal, developing cohort. Brain Structure and Function, 223(1), 211–220. 10.1007/s00429-017-1480-5
    1. Dade L. A., Gao F. Q., Kovacevic N., Roy P., Rockel C., O’Toole C. M., Lobaugh N. J., Feinstein A., Levine B., Black S. E. (2004). Semiautomatic brain region extraction: A method of parcellating brain regions from structural magnetic resonance images. NeuroImage, 22(4), 1492–1502. 10.1016/j.neuroimage.2004.03.023
    1. Desikan R. S., Ségonne F., Fischl B., Quinn B. T., Dickerson B. C., Blacker D., Buckner R. L., Dale A. M., Maguire R. P., Hyman B. T., Albert M. S., Killiany R. J. (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage, 31(3), 968–980. 10.1016/j.neuroimage.2006.01.021
    1. Drane D. L., Yuspeh R. L., Huthwaite J. S., Klingler L. K. (2002). Demographic characteristics and normative observations for derived-trail making test indices. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 15(1), 39–43.
    1. Farias S. T., Mungas D., Reed B. R., Harvey D., Cahn-Weiner D., Decarli C. (2006). MCI is associated with deficits in everyday functioning. Alzheimer Disease and Associated Disorders, 20(4), 217–223. 10.1097/01.wad.0000213849.51495.d9
    1. Fischer B. L., Gunter-Hunt G., Steinhafel C. H., Howell T. (2012). The identification and assessment of late-life ADHD in memory clinics. Journal of Attention Disorders, 16(4), 333–338. 10.1177/1087054711398886
    1. Fischl B., Dale A. M. (2000). Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proceedings of the National Academy of Sciences of the United States of America, 97(20), 11050–11055. 10.1073/pnas.200033797
    1. Ghosh S., Libon D., Lippa C. (2014). Mild cognitive impairment. American Journal of Alzheimer's Disease and Other Dementias, 29(4), 293–302. 10.1177/1533317513517040
    1. Golimstok A., Rojas J. I., Romano M., Zurru M. C., Doctorovich D., Cristiano E. (2011). Previous adult attention-deficit and hyperactivity disorder symptoms and risk of dementia with lewy bodies: A case-control study. European Journal of Neurology, 18, 78–84. 10.1111/j.1468-1331.2010.03064.x
    1. Goodman D. W. (2009). ADHD in adults : Update for clinicians on diagnosis and assessment. Text, 16, 38–47.
    1. Goodman D. W., Mitchell S., Rhodewalt L., Surman C. B. (2016). Clinical presentation, diagnosis and treatment of attention-deficit hyperactivity disorder (ADHD) in older adults: A review of the evidence and its implications for clinical care. Drugs & Aging, 33(1), 27–36. 10.1007/s40266-015-0327-0
    1. Goubran M., Ntiri E. E., Akhavein H., Holmes M., Nestor S., Ramirez J., Adamo S., Ozzoude M., Scott C., Gao F., Martel A., Swardfager W., Masellis M., Swartz R., MacIntosh B., Black S. E. (2020). Hippocampal segmentation for brains with extensive atrophy using three-dimensional convolutional neural networks. Human Brain Mapping, 41(2), 291–308. 10.1002/hbm.24811
    1. Ivanchak N., Fletcher K., Jicha G. A. (2012). Attention-Deficit/Hyperactivity disorder in older adults: Prevalence and possible connections to mild cognitive impairment. Current Psychiatry Reports, 14(5), 552–560. 10.1007/s11920-012-0305-8
    1. Jackson R. L., Hoffman P., Pobric G., Lambon Ralph M. A. (2016). The semantic network at work and rest: Differential connectivity of anterior temporal lobe subregions. Journal of Neuroscience, 36(5), 1490–1501. 10.1523/JNEUROSCI.2999-15.2016
    1. Jak A. J., Bondi M. W., Delano-Wood L., Wierenga C., Corey-Bloom J., Salmon D. P., Delis D. C. (2009). Quantification of five neuropsychological approaches to defining mild cognitive impairment. The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry, 17(5), 368–375. 10.1097/JGP.0b013e31819431d5
    1. Jessen F., Amariglio R. E., Buckley R. F., van der Flier W. M., Han Y., Molinuevo J. L., Rabin L., Rentz D. M., Rodriguez-Gomez O., Saykin A. J., Sikkes S. A. M., Smart C. M., Wolfsgruber S., Wagner M. (2020). The characterisation of subjective cognitive decline. Lancet Neurology, 19(3), 271–278. 10.1016/S1474-4422(19)30368-0
    1. Kessler R. C., Adler L. A., Gruber M. J., Sarawate C. A., Spencer T., Van Brunt D. L. (2007). Validity of the World Health Organization adult ADHD self-report scale (ASRS) screener in a representative sample of health plan members. International Journal of Methods in Psychiatric Research, 16(2), 52–65. 10.1002/mpr.208
    1. Klein M., Silva M. A., Belizario G. O., Rocca C. C. A., Padua Serafim A., Louzã M. R. (2019). Longitudinal neuropsychological assessment in two elderly adults with attention-deficit/hyperactivity disorder: Case report. Frontiers in Psychology, 10, 1119. 10.3389/fpsyg.2019.01119
    1. Klein M., Souza-Duran F. L., Menezes A. K. P. M., Alves T. M., Busatto G., Louzã M. R. (2021). Gray matter volume in elderly adults with ADHD: Associations of symptoms and comorbidities with brain structures. Journal of Attention Disorders, 25, 829–838. 10.1177/1087054719855683
    1. Kooij J. J., Bijlenga D., Salerno L., Jaeschke R., Bitter I., Balázs J., Thome J., Dom G., Kasper S., Nunes Filipe C., Stes S., Mohr P., Leppämäki S., Casas M., Bobes J., Mccarthy J. M., Richarte V., Kjems Philipsen A., Pehlivanidis A. . . ., Asherson P. (2019). Updated European consensus statement on diagnosis and treatment of adult ADHD. European Psychiatry, 56, 14–34. 10.1016/j.eurpsy.2018.11.001
    1. Kovacevic N., Lobaugh N. J., Bronskill M. J., Levine B., Feinstein A., Black S. E. (2002). A robust method for extraction and automatic segmentation of brain images. NeuroImage, 17(3), 1087–1100. 10.1006/nimg.2002.1221
    1. LeRoy A., Jacova C., Young C. (2019). Neuropsychological performance patterns of adult ADHD subtypes. Journal of Attention Disorders, 23, 1136–1147. 10.1177/1087054718773927
    1. Leung H.-C., Gore J. C., Goldman-Rakic P. S. (2002). Sustained mnemonic response in the human middle frontal gyrus during on-line storage of spatial memoranda. Journal of Cognitive Neuroscience, 14(4), 659–671. 10.1162/08989290260045882
    1. Luo Y., Weibman D., Halperin J. M., Li X. (2019). A review of heterogeneity in Attention deficit/hyperactivity disorder (ADHD). Frontiers in Human Neuroscience, 13, 42. 10.3389/fnhum.2019.00042
    1. Michielsen M., Semeijn E., Comijs H. C., van de Ven P., Beekman A. T. F., Deeg D. J. H., Kooij J. J. S. (2012). Prevalence of attention-deficit hyperactivity disorder in older adults in the Netherlands. The British Journal of Psychiatry, 201(4), 298–305. 10.1192/bjp.bp.111.101196
    1. Mostert J. C., Onnink A. M. H., Klein M., Dammers J., Harneit A., Schulten T., van Hulzen K. J. E., Kan C. C., Slaats-Willemse D., Buitelaar J. K., Franke B., Hoogman M. (2015). Cognitive heterogeneity in adult attention deficit/hyperactivity disorder: A systematic analysis of neuropsychological measurements. European Neuropsychopharmacology, 25(11), 2062–2074. 10.1016/j.euroneuro.2015.08.010
    1. Nogueira R., Abolafia J. M., Drugowitsch J., Balaguer-Ballester E., Sanchez-Vives M. V., Moreno-Bote R. (2017). Lateral orbitofrontal cortex anticipates choices and integrates prior with current information. Nature Communications, 8(1), 14823. 10.1038/ncomms14823
    1. Ozzoude M., Ramirez J., Raamana P. R., Holmes M. F., Walker K., Scott C. J. M., Gao F., Goubran M., Kwan D., Tartaglia M. C., Beaton D., Saposnik G., Hassan A., Lawrence-Dewar J., Dowlatshahi D., Strother S. C., Symons S., Bartha R., Swartz R. H., Black S. E. (2020). Cortical thickness estimation in individuals with cerebral small vessel disease, focal atrophy, and chronic stroke lesions. Frontiers in Neuroscience, 14, 1330.
    1. Paloyelis Y., Asherson P. J. (2011). Structural and functional magnetic resonance imaging findings in adults with ADHD. In Buitelaar J. K., Kan C. C., Asherson P. (Eds.), ADHD in adults (pp. 49–65). Cambridge University Press.
    1. Petersen R. C. (2004). Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine, 256(3), 183–194. 10.1111/j.1365-2796.2004.01388.x
    1. Petrides M., Alivisatos B., Evans A. C., Meyer E. (1993). Dissociation of human mid-dorsolateral from posterior dorsolateral frontal cortex in memory processing. Proceedings of the National Academy of Sciences of the United States of America, 90(3), 873–877. 10.1073/pnas.90.3.873
    1. Ramirez J., Gibson E., Quddus A., Lobaugh N. J., Feinstein A., Levine B., Scott C. J., Levy-Cooperman N., Gao F. Q., Black S. E. (2011). Lesion explorer: A comprehensive segmentation and parcellation package to obtain regional volumetrics for subcortical hyperintensities and intracranial tissue. NeuroImage, 54(2), 963–973. 10.1016/j.neuroimage.2010.09.013
    1. Semeijn E. J., Korten N. C. M., Comijs H. C., Michielsen M., Deeg D. J. H., Beekman A. T. F., Kooij J. J. S. (2015). No lower cognitive functioning in older adults with attention-deficit/hyperactivity disorder. International Psychogeriatrics, 27, 1467–1476. 10.1017/s1041610215000010
    1. Sibley M. H., Arnold L. E., Swanson J. M., Hechtman L. T., Kennedy T. M., Owens E., Molina B. S. G., Jensen P. S., Hinshaw S. P., Roy A., Chronis-Tuscano A., Newcorn J. H., Rohde L. A. (2021). Variable patterns of remission from ADHD in the multimodal treatment study of ADHD. American Journal of Psychiatry. 00:00, XX 2021 Advance online publication. 10.1176/appi.ajp.2021.21010032
    1. Smith G. E., Bondi M. W. (2013). Mild cognitive impairment. In Smith G. E., Bondi M. W. (Eds.), Mild cognitive impairment and dementia: Definitions, diagnosis and treatment (pp. 69–133). Oxford University Press.
    1. Sowell E. R., Lu L. H., O’Hare E. D., McCourt S. T., Mattson S. N., O’Connor M. J., Bookheimer S. Y. (2007). Functional magnetic resonance imaging of verbal learning in children with heavy prenatal alcohol exposure. Neuroreport, 18(7), 635–639. 10.1097/WNR.0b013e3280bad8dc
    1. Starck M., Grünwald J., Schlarb A. A. (2016). Occurrence of ADHD in parents of ADHD children in a clinical sample. Neuropsychiatric Disease and Treatment, 12, 581–588. 10.2147/NDT.S100238
    1. Thorell L. B., Holst Y., Chistiansen H., Kooij J. J. S., Bijlenga D., Sjöwall D. (2017). Neuropsychological deficits in adults age 60 and above with attention deficit hyperactivity disorder. European Psychiatry, 45, 90–96. 10.1016/j.eurpsy.2017.06.005
    1. Wåhlstedt C., Thorell L. B., Bohlin G. (2009). Heterogeneity in ADHD: Neuropsychological pathways, comorbidity and symptom domains. Journal of Abnormal Child Psychology, 37(4), 551–564. 10.1007/s10802-008-9286-9
    1. Wilson H., Niccolini F., Pellicano C., Politis M. (2019). Cortical thinning across Parkinson’s disease stages and clinical correlates. Journal of Neurological Sciences, 398, 31–38. 10.1016/j.jns.2019.01.020

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