the feasibility of a structured cognitive training protocol to address progressive cognitive decline...

AJSLP

Research Article

The Feasibility of a Structured CognitiveTraining Protocol to Address Progressive

Cognitive Decline in IndividualsWith Vascular Dementia

Jamie F. Mayer,a Lilli A. Bishop,a and Laura L. Murrayb

Purpose: Cerebral autosomal dominant arteriopathy withsubcortical infarcts and leukoencephalopathy, better knownas CADASIL, is a rare, genetic form of early-onset vasculardementia. The purpose of this study was to use a modifiedversion of Attention Process Training—II (APT–II; Sohlberg,Johnson, Paule, Raskin, & Mateer, 2001) with an individualwith early-stage CADASIL.Method: APT–II, modified to include strategy training, wasapplied in an A-B, multiple-probe design for an individual whohad been diagnosed with early-stage CADASIL. Outcomemeasures included pre–post neuropsychological testing ofattention, memory, and executive function; within-treatmentprobes of visual and auditory attention; and a measure ofsubjective experience of cognitive functioning in daily living.

Results: The participant demonstrated nominal gains on visualand auditory attention probes but improved performance onseveral posttreatment measures of processing speed andexecutive function. The participant also reported substantiallyimproved functional outcomes following the intervention protocol.Conclusion: This case illustrates the potential utility ofbehavioral intervention for individuals with CADASIL andhighlights issues for speech-language pathologists to con-sider when using structured cognitive training protocols inthe setting of progressive cognitive decline. These datasuggest that further controlled studies for treating this popula-tion are warranted.

Key Words: attention, degenerative brain disease, treatment

Cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy, betterknown as CADASIL, is a rare, genetic disorder with

an estimated prevalence of 1.98 to 4.14 per 100,000 adults(Chabriat & Bousser, 2007). It is characterized by anautosomal-dominant mutation in the NOTCH3 gene, causingprogressive degeneration of vascular smooth muscle cells.By the fourth or fifth decade of life, individuals with CADASILexperience repeated small-vessel ischemic events, oftenculminating in classic lacunar syndrome, followed by step-wise deterioration in cognitive function with “pure” sub-cortical vascular dementia (VaD) (Mesulam, Siddique, &Cohen, 2003). The cognitive symptoms reported mostoften in the early stages of CADASIL primarily affect an

individual’s attention, executive function, and processingspeed, suggesting dysfunction in the frontal cortical–subcorticalnetworks (Herve & Chabriat, 2010; Mesulam et al., 2003;Peters et al., 2005); such symptoms are observable evenbefore the first strokes in individuals with the geneticallyconfirmed defect (Amberla et al., 2004). Although variableexpressivity of symptoms has been reported (Lee, Yang, &Soong, 2009), most affected individuals demonstrate markedcognitive decline after age 50 years and a detectable dementiasoon after age 60 years.

At present, there is no known pharmacological or behav-ioral evidence-based treatment for CADASIL (del RíoEspínola et al., 2009; Herve & Chabriat, 2010). However,the following brief review of behavioral intervention re-search for other static and progressive neurological dis-orders will establish the rationale for exploring the effectsof cognitive training for an individual with early-stageCADASIL.

Cognitive Training for Static Neurological DisordersCommonly applied behavioral treatment models for

clients with static, neurogenic cognitive–communicative dis-orders are grounded in the idea that damaged but at least par-tially spared neural networks can be successfully retrained(Rohling, Faust, Beverly, & Demakis, 2009). One approach

aNorthern Illinois University, DeKalbbIndiana University, Bloomington

Correspondence to Jamie F. Mayer: [email protected]

Editor: Carol Scheffner HammerAssociate Editor: Carl Coelho

Received July 6, 2011Revision received December 23, 2011Accepted January 29, 2012DOI: 10.1044/1058-0360(2012/11-0066)

American Journal of Speech-Language Pathology • Vol. 21 • 167–179 • May 2012 • A American Speech-Language-Hearing Association 167

to “retraining” neural networks involves applying structured,cognitive training protocols in which repetitive exercisesdrill various cognitive capacities under increasingly difficultconditions (Rohling et al., 2009; Sohlberg, Ehlhardt, &Kennedy, 2005). Indeed, the provision of cognitive train-ing to individuals with traumatic brain injury has producedprimarily positive outcomes (for large-scale reviews, seeCicerone et al., 2000, 2005, 2011; Lincoln, Majid, & Weyman,2000; and Rohling et al., 2009). Given the prevalence andfunctional impact of generalized cognitive deficits fol-lowing stroke (Barker-Collo et al., 2009; Murray, 2004;Westerberg et al., 2007), researchers have also developedand applied cognitive training programs for stroke sur-vivors. Generally, such studies have endorsed positiveoutcomes for stroke survivors representing a variety of lesionprofiles (e.g., Barker-Collo et al., 2009; Helm-Estabrooks,Connor, & Albert, 2000; Murray, Keeton, & Karcher, 2006;Sinotte & Coehlo, 2007; Sturm & Willmes, 1991; Sturm,Willmes, Orgass, & Hartje, 1997). Although a commontheme across these studies has been a failure of improve-ments on trained or closely related tasks to generalize toeveryday functioning, more encouraging functional outcomeshave been reported when training protocols include goal-based or strategy training activities to augment the trainingexercises (Cicerone, 2002;Murray et al., 2006; Park& Ingles,2001).

Cognitive Training for ProgressiveNeurological Disorders

In the last several decades, researchers have explored theapplication of intervention models used for individuals withacquired, stable cognitive impairments to those with neuro-degenerative diagnoses. A large body of work has foundthat even individuals with moderate-to-severe cognitivedecline can benefit from focused cognitive exercises thatcapitalize on the relatively spared implicit memory pro-cesses and are designed to teach (or reteach) very specificinformation (e.g., Spaced Retrieval Training; Camp &Stevens, 1990). Although generalization to broader aspectsof cognitive function is not expected in these situations(Acevedo & Loewenstein, 2007), recent literature has iden-tified some success in increasing cognitive function on abroader scale and treating or delaying the onset of dementiaby targeting individuals for behavioral intervention in thevery early or predementia stages (i.e., before significantcognitive decline; Belleville, 2008; Jean, Bergeron, Thivierge,& Simard, 2010; Stuss et al., 2007). In fact, the increasingfocus on diagnosing and treating individuals in the pro-dromal or predementia stages of cognitive impairment hasled to the widespread acceptance of the term mild cognitiveimpairment (MCI) as a diagnostic category in and of itself(see Petersen et al., 2009, for a review). Highlighting theimportance of this construct as a focus for treatment research,Petersen et al. (2009) defined MCI simply as “the clinicalstage during which meaningful interventions can take place”(p. 1,448). Although early conceptualizations of MCI fo-cused on its utility only as a prodromal stage of Alzheimer’sdisease, investigators have more recently broadened the scope

of the term to describe the predementia phases of multipleclinical phenotypes, including those of primary degenerative(e.g., Alzheimer’s disease, frontotemporal dementia) orvascular origins (e.g., vascular dementia, CADASIL; Petersenet al., 2009).

A number of MCI studies using cognitive training pro-tocols to improve various processes including episodicmemory, attention, processing speed, visuospatial abilities,and executive function have reported posttraining gainsin objective, experimental cognitive measures as well assubjective perceptions of improvement, with medium tolarge effect sizes (e.g., Belleville et al., 2006; Cipriani,Bianchetti, & Trabucchi, 2006; for reviews, see Belleville,2008; Faucounau, Wu, Boulay, De Rotrou, & Rigaud,2010; Jean et al., 2010). Such training has most often takenthe form of group exercises (e.g., Belleville et al., 2006) orcomputer-based platforms (Cipriani et al., 2006; Galante,Venturini, & Fiaccadori, 2007; Talassi et al., 2007) andappears to be most effective for improving basic cognitiveskills such as attention or processing speed (Belleville,2008; Park & Ingles, 2001). Several studies have reportedgeneralization of training to everyday activities (e.g.,Edwards et al., 2002, 2005), but others, in line with treat-ment outcomes reported for nonprogressive disorders (e.g.,Cicerone, 2002), have stressed the importance of provid-ing direct training of functional skills and strategies inaddition to training of their underlying cognitive processes(Acevedo & Loewenstein, 2007).

In line with accepted principles of brain plasticity (e.g.,Kleim & Jones, 2008), the specificity of training seems tomatter: Studies comparing individuals receiving cognitivetraining to active (e.g., social or computer contact) as wellas no-contact control groups reported gains only in the cog-nitive intervention group (Edwards et al., 2005; Mahnckeet al., 2006; Talassi et al., 2007). The evidence to date, there-fore, supports the provision of cognitive training for indi-viduals with MCI, with the caveat that future studies withlarger sample sizes, standardized outcome measures, anddouble-blind randomized control treatment designs aredesirable (Jean et al., 2010).

Because CADASIL is genetic (i.e., the presence of theNOTCH3mutation can be identified even in presymptomaticindividuals) and autosomal dominant (i.e., many individualswill have an identifiable family history), it is likely thatmany individuals with the disorder can be identified beforethe onset of the moderate-to-severe cognitive impairmentthat marks later stages of the disease. The MCI literaturehas demonstrated that behavioral intervention appears to en-gender the best outcomes when it is implemented beforedevelopment of the moderate-to-severe cognitive declineseen in full-blown dementia (Belleville, 2008), when indi-viduals have treatment needs (i.e., subjective cognitive com-plaints) and still retain the cognitive capabilities to learnand apply new information and strategies (Faucounau et al.,2010). This suggests that individuals with early-stageCADASIL would likely benefit from exogenous strategiessuch as cognitive training to strengthen existing neuralnetworks or form new networks in the face of ongoingischemic small-vessel disease (Kleim & Jones, 2008; Listet al., 2011; Rohling et al., 2009).

168 American Journal of Speech-Language Pathology • Vol. 21 • 167–179 • May 2012

Rationale for the Current Cognitive Training ProtocolOne commercially available cognitive training program is

Attention Process Training—II (APT–II; Sohlberg, Johnson,Paule, Raskin, & Mateer, 2001), which is the upper ex-tension of Attention Process Training (APT; Sohlberg &Mateer, 1986). APT and APT–II target indidivuals’ deficitsin attentional processing, including difficulties coping withdistraction, reduced mental control, and shifting attention.Both programs are designed according to a clinical modelof attention in which attention consists of interrelatedbut separable domains supported by several neural net-works. The treatment model in both programs follows thestimulation or structured cognitive training paradigm, in whichsystematic opportunities for practicing skills are arranged ina graded level of difficulty, similar to the paradigms espousedby theMCI cognitive training literature (e.g., Jean et al., 2010).

As the upper extension of APT, APT–II is designed toincorporate more demanding tasks to address the com-plex attentional deficits associated with mild impairments,such as those seen in mild traumatic brain injury (Sohlberget al., 2001). Therefore, APT–II targets cognitive processesthat are vulnerable even in the early stages of the cognitivedecline associated with CADASIL. APT–II has been usedwith some success in clients with either traumatic braininjury (Palmese & Raskin, 2000) or stroke (Coelho, 2005;Murray et al., 2006; Sinotte & Coehlo, 2007), but not, toour knowledge, in the setting of progressive cognitivedecline. Importantly, this treatment protocol also aims tofoster generalization of the more molecular, hierarchicaltraining exercises to daily functioning by including func-tional exercises toward the end of the treatment protocol.

As the number of individuals identified in the prodromalphases of cognitive decline continues to increase (Petersenet al., 2009), and the evidence for behavioral intervention inthese early phases continues to mount (Belleville, 2008), it islikely that speech-language pathologists (SLPs) will be calledon at an increasing rate to provide services in the setting ofcognitive decline (American Speech-Language-Hearing As-sociation [ASHA], 2005). APT–II is readily available forpurchase and exemplifies the type of cognitive training thathas been used in a number of previous behavioral interventionstudies for cognitive dysfunction of a static or neurodegen-erative nature. Accordingly, the purpose of this exploratorystudy was to test whether APT–II, modified to include a moreprominent strategy training component, could positively in-fluence cognitive function (attention, memory, and executivefunction) and functional outcomes (improved performanceof everyday activities) in an individual with a history ofmultiple small-vessel ischemic infarctions and CADASIL.We hypothesized that the inclusion of strategy training in ourprotocol, following previous recommendations (Acevedo &Loewenstein, 2007; Cicerone, 2002; Murray et al., 2006),would be especially important in the setting of a progressivedisorder as a means for our participant to maintain functionover time. Our research questions were as follows:

• Is modified APT–II a viable treatment option for anindividual with CADASIL as evaluated in terms of abilityto progress through the treatment protocol?

• Will treatment lead to subjective perceptions of cognitiveimprovement?

• Will treatment measurably improve the individual’s atten-tion and executive function, as evaluated via (a) stan-dardized cognitive tests and (b) weekly probes in visualand auditory modalities?

• Will the individual’s treatment effects be maintained overa 6-month follow-up period?

MethodParticipant

SB (initials changed) is a 58-year-old white male with16 years of formal education. He presented with a 10-yearhistory of multiple small-vessel ischemic infarcts and a pos-itive family history of CADASIL, with diagnosis geneticallyconfirmed in September 2010.

Knowing his family history and CADASIL risk, SBunderwent a baseline cognitive assessment 10 years beforethis study in March 1998, at the age of 47. According to theneuropsychological report, SB’s performance at that timewas consistent with mild impairments in verbal learning,delayed recall (free recall paradigms only), and verbalfluency. Of note, these impairments were evident only onthe most sensitive cognitive measures, and no functionalimpairments were evident. A CT scan completed at that timewas consistent with multiple areas of low density bilaterally,especially affecting subcortical and frontal white matter.

SB’s most recent known ischemic event occurred inOctober 2007, È20 months before initiation of this study.He reportedly experienced “difficulty speaking and comingup with words” immediately following this event. Thesedeficits reportedly resolved without behavioral treatmentwithin 1–2 weeks, and SB was able to return to his full-timeposition as the director of education at a local church shortlythereafter. An MRI study that was completed at that timewas consistent with mild to moderate progression of thechanges noted with the CT nearly 10 years before, with“extensive punctate and patchy confluent deep whitematter signal changeIthroughout all lobes of the brainboth subcortical and periventricular in location,” affectingespecially right and left frontal deep white matter, basalganglia, thalami, and pons.

SB was first seen at our university clinic in May 2007for an audiological evaluation, which demonstrated normalhearing up to 2,000 Hz with a sloping, moderately severesensorineural hearing loss in the high frequencies (3000 Hz–8000 Hz) bilaterally. He was given open-fit digital hearingaids at that time and reportedly obtained “excellent” wordrecognition abilities. In January 2009, È14 months follow-ing his last known ischemic event, SB returned to our clinicwith concerns of a worsening hearing loss, reporting increaseddifficulty understanding speech in distracting or noisy envi-ronments. A full audiological evaluation revealed no changein SB’s hearing sensitivity or word recognition abilities, andhis hearing aids were found to be functioning appropriately.Noting that SB’s increased difficulty hearing and/or pro-cessing stimuli in background noise more likely reflected

Mayer et al.: Cognitive Training for CADASIL 169

“concentration” rather than a decrease in actual hearing acuity,the audiology team referred him for a cognitive evaluation.

Pretreatment AssessmentSB completed an initial test battery examining his lan-

guage, attention, memory, and executive function skills inJune 2009. The results of these tests are presented in Table 1.

Tests used to describe selected abilities. Given SB’sreports of language deficits immediately following his 2007ischemic event, we decided to administer the WesternAphasia Battery (Kertesz, 1982) to confirm or rule outaphasia as a contributing factor to his attentional complaints;his WAB aphasia quotient (AQ) of 99.6 substantiated thatany language deficits had fully resolved and supported ade-quate word recognition and auditory comprehension in a

TABLE 1. SB’s pre- versus posttreatment and follow-up testing data.

MeasurePretreatment

(6/09)Posttreatment

(10/09)Follow-up(6/10)

RBMT–3a

Verbal MemoryName 9 N/A N/AStory – Immediate 10 N/A N/AStory – Delayed 8 N/A N/A

Visual MemoryPicture Recognition 11 N/A N/AFace Recognition – Delayed 6d N/A N/A

Spatial MemoryRoute – Immediate 9 N/A N/ARoute – Delayed 9 N/A N/A

Prospective MemoryBelongings – Delayed 12 N/A N/AAppointments – Delayed 12 N/A N/AMessages – Immediate 11 N/A N/AMessages – Delayed 11 N/A N/A

Orientation/Date10 N/A N/A

New LearningNovel Task – Immediate 14 N/A N/ANovel Task – Delayed 10 N/A N/A

WABAphasia quotientb

99.6 N/A N/ATONI – 3c 120 N/A N/AD–KEFSa,d

TrailsCombined Scaled Score (number + letter

sequencing, Conditions 2 & 3)14 14 N/A

Condition 4: number–letter switching 5e 12** N/AContrast scaled score: Combined

number/letter vs. Switching2e 9** N/A

Fluency: VerbalLetter Fluency 8 8 13***Category Fluency 12 7f 14***Category Switching: Total Correct 6f 8 14***Category Switching: Accuracy 7f 9 12*Switching vs. Fluency 4e 11** 10**

Color-Word InterferenceColor Naming 10 10 10Word Reading 10 9 11Inhibition 13 13 13Inhibition/Switching 8 12* 11*Completion Times 10 10 11Inhibition/Switching vs. Inhibition 4e 9* 8*

Note. RBMT = Rivermead Behavioral Memory Test—Third Edition (Wilson et al., 2008), WAB = WesternAphasia Battery (Kertesz, 1982); TONI–3 = Test of Nonverbal Intelligence—Third Edition (Brown, Sherbenou, &Johnsen, 1997), D–KEFS = Delis–Kaplan Executive Function System (Delis, Kaplan, & Kramer, 2001).aM = 10, SD = 3; bCutoff for aphasia ≤ 93.8; cM = 100, SD = 15; dSelected subtest scores reported; eTestsor subtests for which BS scored ≥ 2 SDs below the mean; fTests or subtests for which BS scored ≥ 1 SD belowthe mean.

Reliable change indices are denoted with asterisks: *69% confidence interval, **95% confidence interval,***99% confidence interval.


quiet setting with bilateral hearing aids in place. SB’s per-formance on the Test of Nonverbal Intelligence—ThirdEdition (Brown, Sherbenou, & Johnsen, 1997) was also wellwithin normal limits, although a significant processing delaywas noted (È90 min administration time). Moreover, con-sistent with the notion that frontal–subcortical network im-pairments should affect attention and executive functionrather than memory per se (Amberla et al., 2004; Chabriat& Bousser, 2007), SB scored within normal limits on theRivermead Behavioral Memory Test—Third Edition (Wilsonet al., 2008).

Tests used as outcome measures. SB’s primary areasof difficulty encompassed timed tasks requiring inhibitionand especially cognitive flexibility, as exemplified by hisperformance on subtests of the Delis–Kaplan ExecutiveFunction System (D–KEFS; Delis, Kaplan, & Kramer, 2001).Consistent with prevalent cognitive patterns in CADASIL(Amberla et al., 2004; List et al., 2011; Peters et al., 2005),SB was well within normal limits on the nonexecutiveaspects of the D–KEFS (e.g., visual scanning); it was onlywhen executive or processing speed demands were increasedthat he experienced significant difficulty, with scores muchlower than expected based on his initial performance (asreflected in D–KEFS contrast scores; Table 1). Substantiat-ing these observations, SB identified significant functionaldeficits on the APT–II attention questionnaire (Sohlberget al., 2001), especially in distracting environments or onmulticomponent tasks (Table 2).

It should be noted that SB was taking both Namenda(20 mg per day) and Aricept (20 mg per day) during hisparticipation in this study. However, because he had beenprescribed these medications for È12 months before thestudy started and had maintained a stable dosage with-out noticeable behavioral benefits during this period, thesedrugs were not considered independent variables duringthe course of our study. Consistent with this approach,neither Namenda nor Aricept, nor any other cholinesteraseinhibitor (ChEI), has been approved for individuals withCADASIL (Dichgans et al., 2008; del Río Espínola et al., 2009).

In summary, consistent with early-stage CADASIL, SBdemonstrated mild, high-level cognitive deficits characterized

primarily by slowed processing and attentional and executivedysfunction, but with overwhelmingly intact componentand fundamental skills.

Study DesignDue to the exploratory nature of this study, we chose a

single-subject, A–B design with multiple target measures andfollow-up (Richards, Taylor, Ramasamy, & Richards, 1999).

Treatment ProtocolSB received cognitive treatment for 90-min twice-weekly

sessions, with an additional 60 min/day of home practicerequired, over a period of 10 weeks. Note that this level ofintensity well eclipses that suggested in the APT–II manual,consistent with recent emphases on the importance of inten-sive therapy for generating maximal neural change (Kleim& Jones, 2008; Raymer et al., 2008) and with recommenda-tions for implementing cognitive training for individuals withMCI (Jean et al., 2010).

The first half of each treatment session followed thehierarchy of attention training tasks in the APT–II manual.Following Sinotte and Coehlo (2007), 80% performanceaccuracy over two consecutive trials was required to prog-ress to the next treatment activity. This criterion level waschosen to ensure accurate performance while allowingfor steady progression through the treatment protocol(Murray et al., 2006). The second half of each treatmentsession included strategy training activities (see Table 3for examples) following the recommendations of Cicerone(2002) and Murray et al. (2006). On those APT–II exerciseson which SB failed to achieve the 80% criterion withinfive trials (typically at least one task per session), SB wastaught to use a variety of compensatory strategies to improvehis performance, including rehearsal (e.g., writing downthe task instructions and practicing with novel [clinician-generated] stimuli before completing the task itself), verbalmediation (e.g., repeating each stimulus item after it wasspoken on the CD), anticipation of task demands (e.g., pre-dicting performance by reviewing cognitive demands of thetask), and self-pacing (e.g., performing the task on stimuli

TABLE 2. SB’s performance on the Attention Process Training—II (Sohlberg, Johnson, Paule, Raskin, & Mateer, 2001) attentionquestionnaire at pre- versus posttreatment and follow-up.

Stimulus item Pretreatment (7/09) Posttreatment (10/09) Follow-up (6/10)

Seem to lack mental energy to do activities Sometimes On occasion On occasionAm slow to respond when asked a question or participating in conversations Sometimes On occasion On occasionCan’t keep mind on activity or thought because mind keeps wandering Sometimes On occasion On occasionCan only concentrate for very short periods of time Sometimes On occasion On occasionMiss details or make mistakes because level of concentration decreased Frequently On occasion Not a problemEasily get off track if other people milling about nearby Frequently Not a problem Not a problemEasily distracted by surrounding noise All of the time Sometimes On occasionTrouble paying attention to conversation if more than one other person All of the time On occasion On occasionEasily lose place if task or thinking is interrupted Frequently On occasion On occasionEasily overwhelmed if task has several components Frequently On occasion On occasionDifficult to pay attention to more than one thing at a time Frequently Not a problem Not a problem

Total score 33 11 9

Note. On occasion = <1/week; Sometimes = 1–3 times/week; Frequently = most days.


read aloud by the clinician at a slower pace than that pro-vided on the CD, then gradually working his way up to thespeed at which the stimuli were presented on the APT–IICD). These strategies were explored in a trial-and-errormanner with SB; strategies that appeared promising (i.e.,resulting in measurable improvements in performance rate oraccuracy within several trials) were written down for SB topractice repeatedly during the treatment session, and thosethat did not seem to help were discarded, to be cycled throughas needed with later exercises.

For home practice sessions, SB was given APT–II stimulito practice using the strategy training activities (provided inwritten form) that were found to be most effective at max-imizing his performance for those or similar stimuli duringtreatment sessions. Home practice sessions were designedto mimic treatment sessions, and compliance with homeworkwas monitored via a written log. SB reported high levels ofcompliance with the homework protocol. His performanceon the activities assigned for home practice was measuredat the subsequent treatment session, and his ability to use thetrained strategy was observed. Subjective feedback as tothe utility of the strategy for the attempted exercise wassought, and guided questioning was used to provide SB withopportunities to apply the practiced strategy to other func-tional activities (e.g., using rehearsal and verbal mediationto recall phone messages at work). As treatment progressed,APT–II generalization activities were included in the home-work protocol (Sohlberg et al., 2001).

Outcome MeasuresFeasibility of the treatment protocol. The feasibility of

applying APT–II to an individual with early-stage CADASILwas measured by the rate of SB’s progression through thetreatment protocol: that is, his ability to meet criterion (usingstrategies as necessary) and progress through the hierar-chical exercises within the a priori determined timeframeof 10 weeks (i.e., 20 sessions).

Subjective measures. The primary subjective outcomemeasure was the APT–II Attention Questionnaire (Sohlberget al., 2001), which was administered to SB at baseline,immediately after treatment, and at follow-up. To maximizethe test–retest reliability and minimize expectation (placebo)effects, SB was not allowed to view his previous responsesto the questionnaire at each time point, nor were question-naire outcomes reviewed with him at any point during thestudy.

Cognitive measures. Because SB perceived testingsessions as highly stressful, we used as outcome measuresonly those tests on which he had demonstrated difficulty (i.e.,below normal performance) at the pretreatment assessment.Therefore, cognitive outcome measures included the fol-lowing subtests of the D–KEFS: Trails, Fluency, and Color-Word Interference. SB did not retake the RBMT, TONI–3,or WAB, given that his scores on these measures were wellwithin normal limits before treatment.

Probes. Because APT–II targets both auditory and visualaspects of attention, SB’s attentional abilities were probedacross both modalities throughout the treatment protocol.The specific tasks used (described below) were chosen basedon their strong reliance on processing speed and error mon-itoring, given that these cognitive skills have been reportedto be the most sensitive indicators of cognitive function inclients with CADASIL (Peters et al., 2005). These behaviorswere probed at baseline (×3), at the beginning of every othertreatment session, and at follow-up. Due to technical diffi-culties during several treatment sessions (e.g., unavailabilityof a sound booth for the auditory probe), each probe wasadministered a total of seven times during the treatmentprotocol. As APT–II is designed to target both visual andauditory attention simultaneously, we chose not to staggerour probes to examine specificity of treatment effects;rather, we simply examined whether both aspects of atten-tion appeared to change during and after application of thetreatment protocol, in addition to the measures administeredat pre- and posttreatment sessions only as described above.

TABLE 3. SB’s within-treatment activities and performance data.

APT–II attentiondomain Task examples Example strategies and task modifications

# sessions to reachcriterion

Sustained Level I (Attention tapes): From a word list,identify words with more than one spelling.

None required 2a

Selective Level IV (Attention tapes): From a word list,identify related words separated by unrelatedwords in background noise.

Slowed rate; temporary removal of backgroundnoise; self-cuing by writing stimuli; repeatingeach stimulus aloud immediately followingpresentation; self-pacing (to cue for stimuluspresentation rate) by tapping with each stimulus.

5

Alternating Sentences: Alternate between repeating wordsfrom sentence stimuli in alphabetical order vs.in reverse order.

Writing instructions before each exercise and usingthe written cue to guide answers; temporarilydecreasing number of stimuli to be recalled(below level suggested on APT–II).

10

Divided Complete a math worksheet while simultaneouslycategorizing verbally presented stimuli.

Using self-generated written and verbal cues toguide performance.

4

aBecause SB’s primary complaints involved processing complex auditory stimuli in noise, and because the APT–II selective attention exercises arevirtually identical to the sustained attention exercises (with background noise added), we chose to progress directly to selective attention duringthe second treatment session after it became clear that most of the sustained attention exercises were not challenging enough for SB.


The visual attention probe consisted of an experimentalversion of the n-back task (Kirchner, 1958; Mayer, Murray,& Turkstra, 2007). The n-back is a continuous performancetask in which participants are required to monitor a streamof stimuli for one that matches the stimulus occurring “n”places back in the sequence. SB completed a two-back taskusing pictured object stimuli presented via PsyScope Beta II(Cohen, MacWhinney, Flatt, & Provost, 1993) on a laptopcomputer. The primary test measure is a signal detectionstatistic, “Pr”, which is calculated by subtracting the falsealarm rate from the hit rate (i.e., probability of correctlyselecting a target). SB’s reaction time was also recorded. Tocontrol for exposure effects, SB completed an n-back taskwith a different set of stimuli (i.e., different pictured objects)at baseline and posttreatment sessions only.

The auditory attention probe consisted of the StaggeredSpondaic Word test (SSW; Katz, 1962), which is a measureof central auditory function that is thought to reflect bothattention and working memory (Keller, Tillery, & McFadden,2006; Riccio, Hynd, Cohen, & Molt, 1996). The SSW con-sists of 40 trials in which four words (i.e., two semanticallyrelated word pairs) are presented via headphones in a stag-gered manner, with dichotic presentation (overlap) of thesecond and third words. The participant’s task is to repeat allfour words in order. The primary test measure is percentagecorrect. Due to SB’s hearing loss, we administered the SSWin a double-walled sound booth to maximize hearing sensi-tivity and eliminate any potential background noise. Soundlevel via the headphones was calibrated to SB’s comfortablelistening level for each ear during the first probe, and theappropriateness of this level was re-established at the begin-ning of each probe thereafter. To account for exposure effects,the full 40 trials were administered only during the firstand last probe; the intervening probes consisted of 30 trials.

ResultsWithin-Treatment Performance: APT–II Protocol

As shown in Table 3, SB progressed steadily throughthe modified APT–II program and reached criterion (80%accuracy × 2 per task) with concurrent strategy training andoccasional task modification (e.g., slower presentation rate).Similar to Murray et al. (2006), we found that the hierar-chy of APT–II tasks did not always match the level of diffi-culty experienced by SB; for example, although alternatingattention directly follows the sustained attention level inthe APT–II manual, this level proved quite challenging forSB and thus we addressed it later in his treatment protocolto preserve the hierarchical nature of his training.

Subjective outcomes. As shown in Table 2, SB reportedsubstantially improved functional outcomes after treatment,with his score on the APT–II questionnaire decreasing from33 before treatment to 11 after treatment. SB reported be-coming less frustrated during completion of multicomponenttasks and felt that he would be able to continue working in hiscurrent position pending any medical changes.

Posttreatment testing. As noted above, cognitive outcomemeasures included the following subtests of the D–KEFS:Trails, Fluency, and Color-Word Interference. To circumvent

concerns regarding the reliability of D–KEFS subtests forneuropsychological decision making (Crawford, Sutherland,& Garthwaite, 2008), we calculated reliable change indices(RCI; Devilly, 2004; Jacobson & Truax, 1991) to assessand objectify the degree of change from pre- to posttreatmentusing reliability data from the D–KEFS manual (Delis et al.,2001). As seen in Table 1, SB demonstrated significantchanges from pre- to posttreatment in subtests measuringhigh-level attentional skills (e.g., attention switching), withlittle change to component skills (e.g., letter fluency).

Probe performance. Baseline stability was unfortunatelynot achieved across probes. Because SB found probe tasksto be difficult and experienced a high level of frustrationduring the baseline sessions, we made a clinical judgmentto proceed with the treatment protocol despite SB’s risingbaseline trend. Although this invalidated a number of acceptedsingle-subject outcome measures (e.g., Shewart Chart trendlines; Robey, Schultz, Crawford, & Sinner, 1999), we wereable to use two methods to quantify our results: effect size(Beeson & Robey, 2006) and a time-series analysis, theC statistic (Tryon, 1982, 1984). Effect sizes were calculatedto estimate the magnitude of change from pre- to posttreat-ment. These values were obtained for each probe (visualand auditory) by dividing the difference between baselineaverage (three data points) and posttreatment scores (onedata point) by the standard deviation of the baseline phase.SB’s performance on the n-back (visual attention) probeyielded an effect size of 2.2 from pre- to posttreatment; hisperformance on the auditory (SSW) probe yielded an effectsize of .55. Beeson and Robey (2006) recommended inter-preting the magnitude of a given effect size in the context ofavailable studies directed toward a similar behavior. Accord-ing to a recent review of studies using the n-back task totrain the executive component of working memory (Dahlin,Backman, Neely, & Nyberg, 2009), our effect size of 2.2on the n-back probe was moderate; the improvement on theauditory (SSW) probe was negligible.

The C statistic was calculated to provide an estimate ofwhether the slope of probe scores during the treatment phasediffered significantly from that of the baseline phase (Tryon,1982, 1984). According to initial C-statistic analyses, therewas no significant trend in SB’s untrained baseline phase(n-back baseline: C = .439, z = 1.24, p = .107; SSW baseline:C = .07, z = .19, p = .425). However, the limited numberof baseline observations reduced the likelihood of findinga significant result (Tryon, 1982); therefore, given the visualevidence of ascending baselines, we chose to use the mostconservative application of the C statistic to further analyzeour probe data. This method minimizes Type I error by usingresiduals from the trended baseline and treatment data.

As described by Tryon (1982), we created a comparisonseries by directly subtracting data points in the baseline fromthe treatment phases and calculated the C statistic basedsolely on the comparison series rather than directly com-paring the baseline and treatment phases. Using this method,results were nonsignificant for the n-back task (C = .5, z = 1.43, p = .077) and the SSW test (C = .44, z = 1.25, p = .11).In other words, despite the visual perception of improvedperformance (accuracy) across time in the n-back and SSWprobes (Figures 1 and 2), and the moderate effect size from


pre- to posttreatment for the n-back probe, conservativestatistical analysis demonstrated that the slope of the im-provement in the treatment phase was not significantlydifferent from that of the baseline phase for either probetask.

SB’s performance on the exposure probes (i.e., thosecompleted only before and after treatment) was similarlyequivocal; he demonstrated a slightly improved score on then-back exposure probe, but his score on the initial exposuretask was much higher than that obtained on the treatmentprobe (Figure 1). SB demonstrated no change on the SSWexposure probe (Figure 2). An examination of reaction timedata for the n-back task similarly revealed nominal changeacross the treatment protocol (Figure 3).

Long-term follow-up.Wehad planned to see SB at 6monthsafter treatment; due to scheduling difficulties, he was insteadseen 8 months following cessation of the treatment protocolfor readministration of selected probes and pre/posttreatmenttasks. SB had not received any further behavioral treatment

in the intervening time nor had he changed his medicationregimen, and there was no evidence of any additionalischemic events per his neurologist. As noted in Table 1,SB maintained his improved posttreatment scores across allsubtests and exceeded both pre- and posttreatment measureswith respect to verbal fluency. Similarly, he maintainedhis improved performance (i.e., accuracy) on the visual(n-back) and auditory (SSW) probes (Figures 1 and 2), withslight but insignificant increased reaction time (Figure 3),perhaps representing a favorable speed–accuracy trade-off.SB continued to endorse improved functional outcomes; hisAPT–II questionnaire score remained substantially lowercompared to before treatment and slightly lower than imme-diately after treatment (Table 2).

DiscussionThe results of our study add to the limited existing liter-

ature regarding the feasibility and efficacy of behavioral

FIGURE 1. SB’s accuracy (Pr) on the visual attention probe, the n-back task. The vertical solid linesseparate the three baseline sessions from the treatment and follow-up sessions.

FIGURE 2. SB’s performanceon the auditory probe, the StaggeredSpondaicWord test (Katz, 1962).The vertical solid lines separate the three baseline sessions from the treatment and follow-up sessions.


intervention programs for individuals with mild cognitive–communicative disorders of a degenerative nature. Follow-ing 10 weeks of direct attention training using a modifiedversion of APT–II (Sohlberg et al., 2001), our participantdemonstrated adequate progression through the protocol,significant positive changes on tests measuring high-levelattention skills, and substantial improvement in his confi-dence in his cognitive skills. Importantly, these gains weremaintained at 8 months after treatment. The data from thevisual and auditory attention probes, which were intendedto gauge within-treatment gains, were less clear-cut. SB’srising baseline trend necessitated that these data be analyzedas conservatively as possible; thus, the likelihood of aType II error (i.e., failing to reject a false null hypothesis)was unavoidably increased. Therefore, we cautiously inter-pret our findings as providing support for direct attentiontraining to improve both impairment-level and functionaloutcomes in the context of early cognitive decline (Belleville,2008; Jean et al., 2010), consistent with those of investiga-tions demonstrating positive effects of APT–II for individualswith static neurological impairments (Coelho, 2005; Murrayet al., 2006; Palmese & Raskin, 2000; Sinotte & Coelho,2007).

Our positive findings resonate with theoretical paradigmsendorsing that brain plasticity can be maximized even inthe setting of progressive neuronal or white matter degen-eration (e.g., Louis et al., 2001). Epidemiological researchhas suggested that environmental and lifestyle-related factorsplay a pivotal role along a continuum of brain function fromage-related cognitive changes, to predementia syndromes(MCI), to frank dementia of either degenerative (dementia ofthe Alzheimer’s type) or vascular (VaD, CADASIL) origin(Panza et al., 2005). To date, no effective pharmacological orother medically based treatments have been identified thatunequivocally prevent the progression of MCI to full-blowndementia. Therefore, the role of cognitive training across thisspectrum of cognitive ability cannot be understated. It isimportant to note that SB, consistent with relatively isolateddeficits in frontal cortical–subcortical circuitry (Amberla

et al., 2004), demonstrated high-level attentional and exec-utive deficits in the context of spared memory and learning.Our results therefore support the provision of cognitivetraining as early as possible in the disease process beforesignificant memory deficits accrue and when availablecognitive capacity can be maximized during intervention(Acevedo & Loewenstein, 2007; Belleville, 2008; Petersenet al., 2009).

Study LimitationsThe exploratory nature of our design necessitates that a

number of issues be considered that potentially limit gen-eralizing our outcomes to other individuals with MCI of adegenerative or vascular nature. First, a number of theoret-ically separable factors were necessarily combined in ourtreatment approach. Our multifaceted paradigm (i.e., com-bining APT–II with both strategy training and a signifi-cant home practice component) was chosen to providethe best possible chance of a positive treatment outcome,given available evidence showing that the hierarchical exer-cises provided in APT–II appear to work best when theyare combined with explicit metacognitive strategy training(e.g., Cicerone, 2002; Murray et al., 2006), and that treat-ment intensity (i.e., incorporating home practice) is a crit-ical factor in maintenance and generalization of gains(e.g., Raymer et al., 2008). That said, this approach neces-sarily conflated these theoretically separable factors, andthus the influence of each of these treatment componentson our ultimate outcome would require individual replica-tion with additional participants. Additionally, although wedid not consider our participant’s daily regimen of ChEIsas an independent variable, given the stability of the dosagefor 1 year’s time before initiation of our study, it is possi-ble that these medications ultimately affected our results.Rozzini et al. (2007), in one of the few studies to exam-ine the interaction between ChEIs and cognitive training inMCI, randomized individuals affected with MCI into one ofthree conditions: (a) treatment with ChEIs only, (b) combined

FIGURE 3. SB’s reaction time, in ms, on the visual attention probe, the n-back task. The verticalsolid lines separate the three baseline sessions from the treatment and follow-up sessions.


treatment with ChEIs and computerized cognitive exercises(Sinforiani, Banchieri, Zucchella, Pacchetti, & Sandrini,2004), and (c) no treatment. Consistent with known prin-ciples of brain plasticity (Kleim & Jones, 2008), only theindividuals receiving ChEIs in conjunction with behavioraltreatment demonstrated gains in objectively measured cog-nitive function at the 1-year follow-up mark. The ChEI-onlyand no-treatment control groups did not differ with respect tocognitive function, with the exception of a small improve-ment in depressive symptoms in the former group. Thissupports the idea of cognitive training as a tool to potentiatethe effects of cognitively enhancing medications such asChEIs; following this logic, it is possible that our study’spositive outcomes required cognitive training in conjunc-tion with SB’s medication regimen.

A second important issue is the incompatibility of ourtreatment probe outcomes with the positive results seen onseveral cognitive tests and SB’s subjective perceptions of hiscognition. There are several possible explanations for thispattern of results, which we will consider in the followingorder: (a) poor sensitivity of probe measures (i.e., Type IIerror), (b) test–retest effects (i.e., Type I error), and (c) placebo-induced subjective improvements, based on the nonblindednature of the study.

Probe measures. The visual (n-back) and auditory (SSW)attention tasks were selected based on two factors: (a) ex-pected outcomes of the APT protocol, given its emphasison both visual and auditory attentional mechanisms, and(b) SB’s initial cognitive profile, including evidence that themost sensitive measure of cognitive function in CADASILshould focus on both processing speed and error monitoring.Additionally, SB’s high level of education and presumedhigh level of premorbid intelligence (e.g., his TONI–3 score,Table 1) required that our probe measures be difficult enough(i.e., with consistently low scores at baseline) to providepotentially sensitive indicators of improvement. It is possiblethat SB’s performance on these probe measures did not ade-quately reflect his cognitive progress over the course ofthe study; likewise, it is also possible that our conservativestatistical interpretation of his performance (i.e., the appli-cation of the most conservative version of the C statistic)underestimated potential measurable gains. Replication ofthis study with functional probe measures designed morespecifically to measure processing speed and error moni-toring, and with a clearer connection to everyday function(e.g., SB’s ability to accurately recall a rapidly spokenphone message), might provide a better gauge of true within-treatment progress.

Test–retest effects. Belleville (2008) pointed out thatthe exact endpoint or goal for cognitive training protocols inthe context of progressive cognitive decline is not well de-fined. Conversion to full-blown dementia is a binary end-point, but with very specific diagnostic requirements thatare not technically within the realm of speech-languagepathology (ASHA, 2005). On the other hand, SLPs are wellqualified to select, administer, and interpret assessmentinstruments for the cognitive–communicative disordersassociated with dementia or prodromal dementia (ASHA,2005). Improvement from pre- to posttreatment on cogni-tive tests is desirable, but a number of complicating factors

exist. First, objectively quantifying cognitive problems inmild disorders can be challenging, especially for high-functioning individuals, like SB, who likely scored aboveaverage before disease/disorder onset. Next, practice effectson cognitive tests are a well-known confound (Chein &Morrison, 2010; Crawford et al., 2008; Park & Ingles, 2001).Rohling et al. (2009), for example, found a treatment effectsize of .30 but a test–retest effect size of .41 for cognitivetraining studies employing control (no-treatment) groups.It thus appears critical to include appropriate control groupsor sham conditions when examining cognitive interventionoutcomes. For single-subject studies, an alternative optionis to include specific outcome measures that are expectedto change with treatment in addition to unrelated outcomemeasures that are expected to remain static (Richards et al.,1999). However, although this is a straightforward recom-mendation when treating certain functions (e.g., lexical–semantic retrieval, syntactic comprehension), it is lessclear-cut in cases in which the end goal is remediation ofattention deficits that in theory could influence performanceon most, if not all, higher level tasks (Riccio & French,2004).

When appropriate control groups are unavailable andethical considerations limit applying sham treatment condi-tions, a possible solution is to apply reliable change indices(Devilly, 2004; Jacobson & Truax, 1991), as we used tointerpret our participant’s data. This technique provides ameans for a more cautious interpretation of pre- versus post-intervention test scores by factoring in the imperfect reli-ability of most cognitive tests. Importantly, this calculationcan be applied straightforwardly in clinical practice becauseit requires only standard error of measurement data that areeasily found in a test manual. Including more than one mea-sure for each cognitive function would serve to furtherstrengthen postintervention interpretation of test scores,especially for individuals with very mild disorders for whomcognitive problems are difficult to objectify.

Subjective outcomes: Increasing cognitive function,cognitive self-efficacy, or both? Receiving a diagnosisentailing progressive cognitive decline is understandablydevastating; many individuals in such circumstances expe-rience anxiety, loss of self-confidence, or catastrophic reac-tions (Jean et al., 2010). A critical aspect of such diagnosesis the loss of a feeling of self-control over one’s own cog-nitive function. Cognitive self-efficacy refers to an individ-ual’s beliefs, relative to his or her capabilities, that he or shecan exert control over his or her cognition and thus executenecessary courses of action to satisfy situational demands(Kramer et al., 2003). An internal locus of control has beenshown to be crucial for successful aging in individuals with-out known neurological impairments (Mirowsky, 1997;Wolinsky et al., 2009). This is likely due to the increasedeffort and perseverance necessary for performing everydayfunctions with age (Kramer et al., 2003). Kramer et al.(2003) described low-efficacious individuals as tending to“give up, attribute failure internally, and experience greateranxiety or depression” (p. 216) when faced with challeng-ing tasks. In contrast, high-efficacious individuals tendto “put forth more effort, and persist longer in the face ofaversive stimuli” (p. 216). It follows that a robust sense of


self-efficacy would be especially critical for individualswho are facing a progressive diagnosis such as CADASIL.

Importantly, self-efficacy can be trained or incorporatedinto existing cognitive intervention programs (McDonald-Miszczak, Gould, & Tychynski, 1992). Efficacy-enhancementstrategies such as goal setting, knowledge of progress, exten-sive education regarding outcomes, and modeling havebeen incorporated into studies of exercise regimens forolder adults and have been found to significantly increaseparticipants’ adherence to and benefits from the protocol(Kramer et al., 2003; McAuley, 1993). In retrospect, our useof strategy training in conjunction with APT–II in the cur-rent study inadvertently incorporated a number of suchstrategies. The hierarchical structure of APT–II allowed SBto see clearly his progress in the treatment protocol overtime, and the inclusion of strategy training during treatmentsessions and as homework allowed him to experience suc-cess with the more difficult APT–II exercises and to attri-bute this success to his own abilities. Furthermore, tomaximize compliance with strategy practice, we providedextensive education for SB regarding the nature of his cog-nitive impairment, its neurological underpinnings relativeto CADASIL, and the expected outcomes of our trainingprotocol. Taking these factors into consideration, it is entirelypossible that an enhanced sense of cognitive self-efficacy,rather than or in addition to a true enhancement of cognitiveunderpinnings, accounted for a significant portion of thegains noted in SB. This explanation could also be invoked toexplicate SB’s unexpected increase in verbal fluency at hisfollow-up testing session (Table 1). The design of the currentstudy, however, renders this notion entirely speculative.

The question that naturally arises, then, is whether anincrease in cognitive self-efficacy, leading to improvedperformance on selected cognitive tasks and an improvedperception of performance in everyday activities, is anacceptable outcome of skilled cognitive training. We believethat this question can be answered in the affirmative, givenrecent emphases on personal and contextual factors andon individuals’ abilities to participate fully in life activitiesand roles as crucial cognitive or linguistic treatment outcomes(World Health Organization, 2001), in addition to the factthat no disease-modifying therapy is available for CADASILor other forms of dementia. Replication of this study withthe addition of more specific and personalized subjectiveoutcome measures (e.g., personalizing aspects of the APT–IIquestionnaire with specific measures of frequency of prob-lems during very specific situations) might shed light on thisissue.

ConclusionTo our knowledge, this is the first study to examine be-

havioral treatment for individuals with CADASIL as a viableoption to slow cognitive decline and/or improve function.Building on evidence-based interventions developed forother client populations with progressive or static disorders(e.g., Belleville et al., 2006; Cicerone, 2002; Sohlberg et al.,2001, 2003), the protocol included a combination of for-mal cognitive and strategy training to foster generalization.This study’s major contribution is that it demonstrates the

potential use of a behavioral treatment for people with de-generative cognitive disorders; stronger statements regard-ing the utility of this protocol for early-stage CADASILor vascular dementia await replication with additional par-ticipants. We suggest that this study may serve to furtherjustify the notion that individuals with neurodegenerativedisorders deserve to receive focused, theory-based inter-vention to strengthen the neural networks underlying cog-nitive function (Louis et al., 2001), and recommend thatfurther, controlled investigations be pursued.

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DOI: 10.1044/1058-0360(2012/11-0066) 2012;

2012;21;167-179; originally published online Feb 21, Am J Speech Lang Pathol Jamie F. Mayer, Lilli A. Bishop, and Laura L. Murray

Progressive Cognitive Decline in Individuals With Vascular Dementia

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