Original Resear rch Article Dement Gerat Cogn Dt oO: 101159/000112476 5jsord 200825:109-114 ‘cep ater eis: Otc 22007 Perseveration in Alzheimer’s Disease S.Pekkala®* MLL. Albert®* A. Spiro Ill" T. Erkinjuntti® Departments of *Speech Sciences and Neurology Univers of Heli ki Helsink Finland Medical Research Service and “Noemative Aging Study, VA Boston Healthcare Syste, and “Department of Neurology, Boston University Schoo! of Medicine, ond ‘Department of Epidemiology, Bost Boston, Mass, USA Key Words Recurrent perseveration «Stuck in-set perseveration - Continuous perseveration » Semantic verbal fluency task Alzheimer's disease Abstract Background/Aims and Methods: Perseveration is common Jn Alzheimers disease (AD). We document the type and quantitative burden of perseveration as cognitive decline ‘progresses from normal aging (n= 30) through mild AD (n= 20) to moderate AD (n=20) by administering asemantic ver- bal fluency task. Results: We found perseveration toinerease significantly with increasing severity of AD and different ‘pes of perseveration that distinguish the subject groups in 2 statistically significant manner. Recurrent and continuous perseverations appear early in AD. As the disease progresses Inseverity ntomoderate stage, the number of recurrentand continuous perseverations increases, and stuck-in-set per- severations emerge. Conclusion: The different types of per- severation are likely to reflect the progressive deterioration of different brain regions in AD. aeygh ©2007 Karger 6 Bast Introdu Perseveration, any continuation or recurrence of an «earlier verbal or nonverbal response without an appropri- ate intervening stimulus [1,2], is common in neurologic ton Univesity School of Public Health, disorders. For example it has been examined in aphasia (1-5, Parkinson disease (6, 7, traumatic brain injury [8, 9 and Alzheimer's disease (AD) [5-7, 10-13) It may also be found among normal individuals [2,4 6,14 15). (Over the years 2 principal classification schemes have emerged to describe and explain perseverative phenom- ena, One of these, championed by Goldberg and col- leagues [16-20], states that perseverations are produced by a single neurocognitive mechanism, the ‘pathological inertia’ of cognitive processes, which manifests itself as an inability to complete the previous activity and to switch from one cognitive or behavioral activity to an- other, and i linked primarily to frontal system dysfunc- tion. The other, originally proposed by Sandson and Al- best [1, 2), further developed by Helm-Estabrooks and colleagues (14, 21-23] and recently supported by Po: et al. [24], suggests that there are 3 different forms of per severation, recurrent, stuck-in set and continuous, each linked to a specific neuroanatomical network and each influenced by a different neurochemical profile. For the present study we have adopted the Sandson! Albert model, summarized as follows. Recurrent per- severation is an unintentional, immediate or delayed, repetition of a previous response after an intervening, stimulus. For example, on a semantic verbal fluency task (word list generation task) a subject may say ‘hat, belt ti, hat... Recurrent perseverations have been linked to left temporo-parietal lesions (1,2, 15) and to dysfunction in systems and may result from postactivation of normally inhibited memory traces (4, 25]. Recurrent KARGER _ em7S ae Ano Ehddiegrta cs Acneonana ron a 13084)Tob: Demogea: ds be tices Ne IAD moAD Ststin (=x) (a=2) n=) See aa Femleimale we 18s 399 «2~~*~C6 Aegean ‘can 667155) ¢80(103) 674i) 0a 2.87 0si7 Range core Sal Sos avert, years ‘Mean 9.73.3) 105 (3.7), 10.1 (3.6) 0.28 267 0.75 ange a el 20 Mose Men 289109) 235020) 15924) 84 2.67 oom Range 0) ara Figures in parentheses are standard deviations. NC = Normal control subjects; miAD = mild AD subjects; smoAD = moderate AD subjects; MMSE = Mit perseverations occurring in the semantic verbal fluency task have also been associated with working memory functions, mediated by frontal regions [26, 27), a least in people with alow versus high working memory capacity {28} and in conditions where working memory has been heavily loaded by competing semantically related infor- ‘mation (29] of when working memory was impaired due to AD [30 Stuck-in-set perseveration is the inappropriate main- tenance of a current category or framework of activity after introduction of a new task. For example, a subject ‘may continue to name clothing after being asked to name fruits on the semantic verbal fluency task, Stuck-in-set perseveration has been linked to frontosubcortical and ‘mesolimbic lesions (1, 31] and/orleft anterior prerolandic lesions [15] and to dopaminergic system dysfunction. It may occur as a consequence of impaired integration of ‘multiple inputs and disturbed executive system function such that actions become dissociated from intent. ‘Continuous perseveration is the abnormal prolonga- tion or continuation of a current behavior without inter- ruption by any intervening stimulus. For example, a par- ipant may continuously produce the word ‘hat’ (eg. hat, hat, hat...) on the semantic verbal fluency task Continuous perseveration has been linked to right-hemi- sphere (especially posterior) damage and to impaired noradrenergic systems (1 2, 31)- It may be caused by di turbed attentional mechanisms and an impairment in ‘motor output characterized by postfaciltation of motor impulses. ni-Mental State Examination Although perseveration has long been recognized as a common phenomenon in AD, we thought that a fine- grained analysis of the type and quantity of perseveration in AD might be of theoretical and clinical relevance. [dentifying the different types of peseveration may help clinicians tage the phase of AD in individuals with this, disorder. We hypothesized (1) that recurrent and contin- ‘uous perseveration would emerge in early stages of AD because of the early involvement of the left and right tem- poro-parietal regions; (2) that recurrent and continuous, perseveration would increase in severity as the disease progressed in severity, and (3) that stuck-in-set persever: ation would appear later in the course of AD, asthe fron- tal systems become more affected. ‘We tested these hypotheses with a semantic verbal flu- ency task (a word list generation test)in which 4 semantic categories were administered to patients with AD and to age-matched normal controls. Methods Portcpans ‘Atta 70 subjects participated inthis: 20 with prob able mild AD,20 wit probable moderate AD nd 30 eat deri people ce bl 1). The dsgooas of AD was Based om he NINGDS-ADRDA erteria for probable AD 22) “he Mint Ment State amination (MMSE) [9th Cli 20 Lamar M, Podel K, Carew TC, Cua BS. hlatey1994371309-1598 Albert ML, Sanéson J: Pesevraton in 12 Traphov1, BaodcS, Rows N,Ltout Rice D, Snag A Riga AS Patterns of me ‘ory impairment and peseverative behavior ‘Scene cay Alain’ disease from Subcorteal vascular dementia. J Newol Sei 2 sol pp09-352. 13 Tester AI Sulnoa DP. McCullough, Butters {NeAcamparsonal he category fancy det isis associated with Alstemer’s and Hu- 22 Holt G, Helm-EstabrooksN:Perseveation Aingtns disease Brain Lang 989.9300 Ramage A, Bayles K, Helm Estabrook N, (Crue Frequeny of perseveration In nor ‘mal subjects, Bran Lang 1999-6;529-340 SibrA, fans RD: Letter and semantic Qu 15 Vili Dien peseveraions in ver Burr WS, Blder RM, Goldberg, Kaplan E, Makheree & The neuropsjcology of schizophrenic speck. | Commun Disord 17 Goldberg E: Varieties of perseveration: a STi ‘omparion of two taxonomies | Cin Exp 26 Patless EGoldaceB, Silo, Cuppa Gi- ‘Neuropsychol 19868710-726 Dasle-ar, 1 Goldberg E: The Executive Brain, From bes and the Civilized Mind New Yor, ‘Oxford University ress, 200 deterioration of both temporoparietal regions. (3) Stuck- in-set perseveration emerges in moderate AD, most like- ly because of progression of the disease to involve the frontal systems. (4) The significant increase of recurrent perseveration in mild AD could also be an indication of impaired working memory function, implying that dam- age tothe frontal region may take place at an early stage of the disease. ‘Acknowledgments ‘We would like to thank Anu Airola for her contribution tothe interrater reliability analysis. This study was supported by the Finnish Cultural Foundation, the Academy of Find (project, ‘No. 213023,8.P), and the Medical Research Service, Department ‘of Veterans Affairs and the Nationa Instituteon Aging (grant No, ‘AG 14345:"Language inthe Aging Bratt, M.LA). 19 Goldberg Tucker D: Motor perseveration: sd the levels of encoding a visual fra. | ‘lin Neuropsychol 197834273-288, Resh R. Kennedy C, Goldberg, Kaplan E, Lon DI: Perscveratie fehavor in Ale Timers disease and subcortical ischemic vascular dementia, Neuropsychology 197; Isn-si, Helm-Etabrooks N, Bayles KA, Bryant Fourlormsaf perseveration in dementia nd aphasia putin and normal lees. 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