The role of working memory impairment in ADHD - new therapeutic indications
Zimbul Albo 1  
,   Alan Lerner 1
More details
Hide details
Center for Memory and Cognition, Department of Neurology, Case Western Reserve University, Cleveland, OH USA
Zimbul Albo   

MD, PhD, Center for Memory and Cognition, Department of Neurology, Case Western Reserve University, Cleveland, OH, USA.
J Pre Clin Clin Res. 2008;2(1):1–5
Many individuals affected with Attention Deficit Hyperactivity disorder (ADHD) are faced with a constellation of symptoms and few therapeutic options. Although most of the drugs currently available for treatment are effective to some degree and target the inattention component, they lack the specificity needed to treat cognitive symptoms. Many patients complain of memory deficits as part their inability to cope with daily activities. We review here some concepts of working memory impairment in ADHD, and attempt to apply it to new therapeutic strategies that might prove valuable for treatment. Rivastigmine, a slowly reversible inhibitor of acetylcholinesterase and butyrylcholinesterase, could alleviate the cognitive symptoms of impaired attention (possibly improving working memory function) of patients with ADHD through their action on the prefrontal cholinergic system. Rivastigmine is currently used to improve cholinergic neurotransmission and cognitive function in Alzheimer’s disease (AD). Our discussion is aimed at broadening the spectrum of clinical diagnosis that could potentially benefit from it.
Szatmari P: The epidemiology of attention-defi cit hyperactivity disorders. Child Adolesc Psychiatr Clin N Am 1992, 1, 361-371.
Rowland AS, Lesesne CA, Abramowitz AJ: The epidemiology of attention-defi cit/hyperactivity disorder (ADHD): a public health view. Ment Retard Dev Disabil Res Rev 2002, 8(3), 162-170.
Barbaresi WJ, Katusic SK, Colligan RC: How common is attentiondefi cit/hyperactivity disorder? Incidence in a population-based birth cohort in Rochester, Minn. Arch Pediatr Adolesc Med 2002, 156(3), 217-222.
Barkley RA, Murphy KR, Fischer M: ADHD in adults: What science says. The Guilford Press 2008, (Chapter 2: A revised Neuroanatomy of Frontal-Subcortical Circuits), 9-25.
Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, Faraone SV, Greenhill LL, Howes MJ, Secnik K, Spencer T, Ustun TB, Walters EE, Zaslavsky AM: The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006, 163(4), 716-723.
Wender PH, Wolf LE, Wasserstein J: Adults with ADHD: an overview. Annals of the New York Academy of Sciences 2001, 931, 1-16.
Wilens TE, Biederman J, Spencer TJ: Attention defi cit/hyperactivity disorder across the life span. Ann Rev Med 2002, 53, 113-131.
Faraone SV, Biederman J, Spencer T: Attention-defi cit/hyperactivity disorder in adults: an overview. Biol Psychiatry 2000, 48, 9-20.
Quinn PQ and Nadeau KG: Gender Issues and AD/HD: Research, Diagnosis and Treatment. Silver Spring, MD. Advantage Books 2002.
Searight HR, Burke JM, and Rottnek F: Adult ADHD: Evaluation and treatment in family medicine. Amer Fam Phys 2000, 62, 2077-2086.
Szymanski ML, Zolotor A: Attention-defi cit/hyperactivity disorder: management. Amer Fam Phys 2001, 64, 1355-1362.
DiScala C, Lescohier I, Barthel M, Li G: Injuries to children with attention defi cit hyperactivity disorder. Pediatrics 998, 102, 1415-1421.
Guevara JP, Stein MT: Evidence-based management of attention defi cit hyperactivity disorder. BMJ 2001, 223, 1232-1235.
Brown RT, Freeman WS, Perrin JM: Prevalence and assessment of attention-defi cit/hyperactivity disorder in primary care settings. Pediatrics 2001, 107(3), 43.
Applegate B, Lahey BB, Hart EL: Validity of the age-of-onset criterionfor ADHD: a report from the DSM-IV fi eld trials. J Am Acad Child Adolesc Psychiatry 1997, 36, 1211-21.
Mellers JD, Bullmore E, Brammer M, Williams SC, Andrew C, Sachs N, Andrews C, Cox TS, Simmons A, Woodruff P: Neural correlates of working memory in a visual letter monitoring task: an fMRI study. Neuroreport 1995, 7(1), 109-112.
Woodman GF, Luck SJ, Schall JD: The role of working memory representations in the control of attention. Cereb Cortex 2007, 17, Suppl 1, i118-i124.
Johnson JS, Hollingworth A, Luck SJ: The role of attention in the maintenance of feature bindings in visual short-term memory. J Exp Psychol Hum Percept Perform. 2008, 34(1), 41-55.
Rossi AF, Bichot NP, Desimone R, Ungerleider LG: Top down attentional defi cits in macaques with lesions of lateral prefrontal cortex. J Neurosci 2007, 27(42), 11306-11314.
Tanji J, Hoshi E: Role of the lateral prefrontal cortex in executive behavioral control. Physiol Rev 2008, 88(1), 37-57.
Sheridan MA, Hinshaw S, D’Esposito M: Effi ciency of the prefrontal cortex during working memory in attention-defi cit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007, 46(10), 1357- 1366.
Shimamura AP: Memory and the prefrontal cortex. Annals of the New York Academy of Sciences 1995, 769, 151-159.
Stevens MC, Pearlson GD, Kiehl KA: An FMRI auditory oddball study of combined-subtype attention defi cit hyperactivity disorder. Am J Psychiatry 2007, 164(11), 1737-1749.
Brocki KC, Nyberg L, Thorell LB, Bohlin G: Early concurrent and longitudinal symptoms of ADHD and ODD: relations to diff erent types of inhibitory control and working memory. J Child Psychol Psychiatry 2007, 48(10), 1033-1041.
Barkley RA, DuPaul GJ, McMUrray MB: Comprehensive evaluation of attention defi cit disorder with and without hyperactivity as defi ned by research criteria. Journal of Consulting and Clinical Psychology 1990, 58(6), 775-789.
Hale TS, Bookheimer S, McGough JJ, Phillips JM, McCracken JT: Atypical brain activation during simple & complex levels of processing in adult ADHD: an fMRI study. J Atten Disord 2007, 11(2), 125-140.
Ehlis AC, Bähne CG, Jacob CP, Herrmann MJ, Fallgatter AJ: Reduced lateral prefrontal activation in adult patients with attention-defi cit/ hyperactivity disorder (ADHD) during a working memory task: A functional near-infrared spectroscopy (fNIRS) study. J Psychiatr Res 2008, Jan 26 (accepted for publication; Abstract ahead of print).
Zhu CZ, Zang YF, Cao QJ, Yan CG, He Y, Jiang TZ, Sui MQ, Wang YF: Fisher discriminative analysis of resting-state brain function for attention-defi cit/hyperactivity disorder. Neuroimage 2007, Dec 3 (accepted for publication; Abstract ahead of print).
Mulder MJ, Baeyens D, Davidson MC, Casey BJ, van den Ban E, van Engeland H, Durston S: Familial vulnerability to ADHD aff ects activity in the cerebellum in addition to the prefrontal systems. J Am Acad Child Adolesc Psychiatry 2008, 47(1), 68-75.
Valera EM, Faraone SV, Biederman J, Poldrack RA, Seidman LJ: Functional neuroanatomy of working memory in adults with attentiondefi cit/hyperactivity disorder. Biol Psychiatry 2005, 57(5), 439-447.
Durston S, Mulder M, Casey BJ, Ziermans T, van Engeland H: Activation in ventral prefrontal cortex is sensitive to genetic vulnerability for attention-defi cit hyperactivity disorder. Biol Psychiatry 2006, 60(10), 1062-1070.
Wodka EL, Mahone EM, Blankner JG, Larson JC, Fotedar S, Denckla MB, Mostofsky SH: Evidence that response inhibition is a primary defi cit in ADHD. J Clin Exp Neuropsychol 2007, 29(4), 345-356.
Madera-Carrillo H, González-Garrido AA, Gómez-Velázquez FR, Enríquez-de Rivera DZ: Quantitative electroencephalogram analysis confi rms the presence of frontal lobe defi cit among attention defi cit disorder with hyperactivity children. Gac Med Mex 2007, 143(5), 391- 400.
Clarke AR, Barry RJ, McCarthy R, Selikowitz M, Johnstone SJ, Hsu CI, Magee CA, Lawrence CA, Croft RJ: Coherence in children with Attention-Defi cit/Hyperactivity Disorder and excess beta activity in their EEG. Clin Neurophysiol 2007, 118(7), 1472-1479.