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Alzheimer Disease and Associated Disorders

Vol. 15, No. 1, pp. 19


2001 Lippincott Williams & Wilkins, Inc., Philadelphia

Cognitive Intervention in Alzheimer Disease: A Randomized


Placebo-Controlled Study

*Robert N. Davis, *Paul J. Massman, and Rachelle S. Doody


*Department of Psychology, University of Houston, Houston, Texas, U.S.A.; and Baylor College of Medicine,
Houston, Texas, U.S.A.

Summary: The efficacy of a cognitive intervention consisting of training in face-name


associations, spaced retrieval, and cognitive stimulation was tested in a sample of 37
patients (16 men, 21 women) with probable Alzheimer disease (AD). Patients with AD
were randomly assigned to receive either the cognitive intervention or a mock (pla-
cebo) intervention for 5 weeks. The placebo group then crossed over to receive the
intervention. During the intervention, AD patients showed significant improvement in
recall of personal information, face-name recall, and performance on the Verbal Series
Attention Test. Improvement did not generalize to additional neuropsychologic mea-
sures of dementia severity, verbal memory, visual memory, word generation, or motor
speed, or to caregiver-assessed patient quality of life. Results suggest that although
face-name training, spaced retrieval, and cognitive stimulation may produce small
gains in learning personal information and on a measure of attention, improvement
does not generalize to overall neuropsychologic functioning or patient quality of life.
Key Words: Alzheimer diseaseCognitive interventionDementia
Neuropsychology.

Alzheimer disease (AD) is a progressive dementing long-term projected total losses to the U.S. economy as-
illness affecting approximately 5 to 10% of the popula- sociated with AD have been estimated at $1.75 trillion
tion older than 65 years of age and as many as 50% of (Ernst and Hay, 1994). Therefore, any significantly ef-
those older than 85 years of age (Kaplan and Sadock, fective treatments that delay the progression of the dis-
1995). Initial manifestations of AD include subtle ease should decrease costs to patients, caregivers, and
memory loss and forgetfulness, which progress to pro- society as a whole in addition to improving patient and
found memory loss, cognitive dysfunction, and behav- caregiver quality of life.
ioral and emotional disturbances that may eventually in- Whereas some pharmacologic therapies such as done-
terfere with the patients ability to perform basic activi- pezil have shown early progress in treating the cognitive
ties of daily living. These sequelae culminate in a patient decline associated with AD (Rogers et al., 1998), patients
who requires increasing levels of care throughout the and their families often ask if anything can be done at
course of the illness and 24-hour supervision in its final home to help the patient to function better, even if only
stages. An estimated 4 million people in the United temporarily. Numerous cognitive training programs have
States alone have AD, and as many as 9 million may been developed in an attempt to slow or reverse AD-
have the disease by the year 2040 (Evans, 1994). The related cognitive decline and have reported varying de-
grees of success (Backman, 1992, 1996; Camp et al.,
1996; Gagnon, 1996). Because several of these programs
Received March 5, 1999. Revised December 29, 1999. have been reviewed in detail elsewhere, only the most
Accepted May 17, 2000. promising interventions are summarized here.
Address correspondence and reprint requests to Robert N. Davis,
M.A., Department of Psychology, University of Houston, Houston, TX First, the spaced-retrieval method (Camp, 1989) is a
772045341, U.S.A., or robnd@uh.edu. procedure that facilitates learning and retaining informa-

1
2 R. N. DAVIS ET AL.

tion by recalling that information over increasingly 1988) and on a composite measure of word fluency. In
longer periods. In this approach, patients are taught some contrast, patients receiving passive stimulation and wait-
information and then repeatedly tested on it over time. list controls declined on these measures. Moreover, pa-
When a successful retrieval is made, the interval preced- tients in both treatment conditions improved slightly on
ing the next recall test increases. When a retrieval failure a composite measure of nonverbal memory, whereas the
occurs, the patient is given the correct response and control group declined on this measure. Patients in both
asked to repeat it. treatment conditions also exhibited fewer behavioral
Spaced-retrieval interventions have been found to im- problems compared with the patients in the control
prove retention of names of common objects (Abrahams group. No significant differences were found among
and Camp, 1993), face-name associations (Camp and groups on measures of problem solving or verbal
Stevens, 1990), object-location associations (Camp and memory. After 9 months of follow-up without continued
Stevens, 1990), and performance on a prospective intervention, the original active group returned to base-
memory task (Camp et al., 1996; McKitrick et al., 1992) line on those measures it had improved on after treat-
among patients with AD. Interventions using spaced re- ment, whereas the other two groups fell below baseline
trieval may be advantageous for AD patients because on almost all measures (Quayhagen et al., 1995).
they seem to require little cognitive effort (Camp and Although these results are encouraging, they are some-
Stevens, 1990). Moreover, there is some evidence that what difficult to interpret for two reasons. First, the au-
the spaced-retrieval method relies on implicit memory thors used composite scores derived from several mea-
(Camp et al., 1996), that is, knowledge expressed in per- sures of each outcome domain. For example, scores on
formance that does not require conscious awareness the memory factor of the Mattis Dementia Rating Scale
(Schachter et al., 1988), which seems to be relatively were aggregated with scores on Logical Memory (LM) I,
Figural Memory, and Visual Reproduction (VR) from
intact in AD (Maki, 1995).
the Wechsler Memory ScaleRevised (WMS-R; Wech-
Although spaced retrieval seems to be a promising
sler, 1987), from which a memory composite score
intervention for memory decline in AD, virtually all
was calculated. The psychometric properties of these
studies of its efficacy have used small (n < 10) sample
composite scores are unknown, and no precedent ex-
sizes, have not used control groups, have not randomly
ists for aggregating these scores in such a manner. More-
assigned patients to conditions, and have not used asses-
over, it is not clear on which specific measure(s), if any,
sors blind to condition. Moreover, it is unclear if pa-
the groups differed. Second, the authors report only the
tients gains after spaced-retrieval interventions general-
results of their omnibus F-tests (group time) but no
ize to psychometric improvement or improvement in follow-up test results. It is therefore impossible to deter-
quality of life. mine which groups, if any, differed from one another at
Second, some cognitive stimulation programs have each time point (before treatment, after treatment, and at
demonstrated efficacy among patients with AD (Breuil et 9-month follow-up).
al., 1994; Quayhagen et al., 1995). For example, Quay- In another test of the efficacy of cognitive stimulation,
hagen et al. (1995) randomly assigned 78 family dyads 56 patients with dementia (not necessarily AD) were
(one AD patient plus one family caregiver) to active randomly assigned to receive either 10 cognitive stimu-
cognitive stimulation, passive cognitive stimulation, or a lation sessions over 5 weeks or no treatment (Breuil et
wait-list control group. All families in the treatment al., 1994). Cognitive stimulation sessions relied strongly
groups received weekly training visits by members of the on mental imagery to stimulate encoding, consolidation,
research team, who trained patients and their caregivers and retrieval of information. At follow-up, the interven-
to implement various cognitively stimulating activities. tion group had significantly higher scores on the Mini-
Active cognitive stimulation occurred daily for 60 min- Mental State Examination (MMSE; Folstein et al., 1975)
utes 6 days per week across 12 weeks and consisted of and marginally significant improvement on word list
memory, problem-solving, and conversation activities. memory from the Consortium to Establish a Registry for
Passive cognitive stimulation differed from active cog- Alzheimers Disease battery (Morris et al., 1989). Pa-
nitive stimulation only in that the patient was exposed to tients in the intervention group improved an average of
passive observation of the activity without enforced par- 1.4 points on the MMSE and 1.1 points on word list
ticipation. memory from before to after treatment. No significant
After the intervention, patients receiving active stimu- differences emerged on a measure of verbal fluency, and
lation exhibited improvement in overall cognitive func- scores on five other measures were not analyzed because
tioning on the Mattis Dementia Rating Scale (Mattis, of ceiling or floor effects.

Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001


COGNITIVE INTERVENTION IN AD 3

Training in face-name associations has also demon- SUBJECTS AND METHODS


strated effectiveness for AD patients (Kesslak et al.,
1997). In one study, 11 AD patients and their relatives Participants
(who served as controls) participated in a 4-week inter- Thirty-seven patients (16 men, 21 women) partici-
vention targeting face-name recall. Patients and their pated in the study. All patients were diagnosed with
relatives were seen as a group and received instruction in probable AD by National Institute of Neurological Com-
strategies for face-name rehearsal. Photographs were municative Disorders and StrokeAlzheimers Disease
taken of each group member, and participants practiced and Related Disorders Association criteria (McKhann et
recalling each group members name when shown a pho- al., 1984). The patients were randomly assigned to one of
tograph. To facilitate face-name identification, each two groups: a 5-week intervention group or a 5-week
group member discussed his or her interests, family, and placebo group. The placebo group (6 men, 12 women)
background in the groups presence to facilitate deep had a mean educational level of 12.97 years (SD 2.56)
processing. This intervention yielded significant im- and a mean age of 72.56 years (SD 7.62). The inter-
provement in face-name recall among AD patients as vention group (10 men, 9 women) had a mean educa-
well as improvement on the Geriatric Depression Scale tional level of 15.06 years (SD 3.86) and a mean age
(GDS; Yesavage et al., 1983) and a digit copying task of 68.67 years (SD 3.86). At baseline, the placebo
(Kesslak et al., 1997). Another intervention that used group had a mean MMSE score of 22.78 (SD 4.45),
face-name rehearsal among AD patients also yielded im- and the intervention group had a mean MMSE score of
proved face-name recall using highly similar procedures 21.84 (SD 4.03). Both groups scored within the nor-
(Sandman, 1993). mal range on the GDS: the placebo group had a mean
Although cognitive stimulation and face-name train- score of 5.67 (SD 7.11), and the intervention group
ing seem to be promising interventions for memory de- had a mean score of 4.37 (SD 2.27). None of these
cline in AD, most studies conducted thus far have not minor group differences was statistically significant.
included adequate measures of neuropsychologic func- Regarding medication use, five patients in the inter-
tioning and/or patient quality of life. In some cases, even vention group and four patients in the placebo group
when psychometric improvement is detected, it remains were taking anti-dementia medication (donapezil [Ari-
unclear as to whether the changes are detectable to care- cept; Pfizer] or tacrine [Cognex; Parke-Davis]). Five pa-
givers or actually influence the patients daily function- tients in the intervention group and two patients in the
ing. Moreover, as noted previously, the outcome mea- placebo group were taking antidepressant medication,
sures used in some of these studies have been difficult to mainly fluoxetine (Prozac; Eli Lilly and Co.) or sertraline
interpret. (Zoloft; Roerig).
In the current study, we sought to conduct a rigorous Finally, two patients in each group were taking minor
test of a cognitive intervention that included the most tranquilizers. The relative frequencies of patients taking
promising cognitive interventions for AD patients ac- these various medications did not differ significantly be-
cording to past literature: face-name training, spaced re- tween the intervention and placebo groups.
trieval, and cognitive stimulation. We included measures
Materials
of face-name recall and recall of personal information as
well as a battery of neuropsychologic tests (administered MMSE
by examiners blind to treatment condition) and a care- The MMSE (Folstein et al., 1975) is a 30-item assess-
giver rating scale to assess patient quality of life. Patients ment of cognitive status. It was administered according
with AD were randomly assigned to receive either the to standardized procedures.
cognitive intervention or a mock (placebo) intervention. WMS-R Logical Memory
The placebo group crossed over to receive the interven-
Immediate and 30-minute WMS-R Logical Memory
tion after the original intervention group had been
(CLM; Wechsler, 1987) delayed recall was tested. Test-
treated. Based on previous findings, we hypothesized
ing was administered according to standardized proce-
that patients would exhibit enhanced face-name recall
dures.
and recall of personal information after receiving the
cognitive intervention. Furthermore, we hypothesized WMS-R Visual Reproduction
that the cognitive intervention would improve neuropsy- Immediate and 30-minute WMS-R Visual Reproduc-
chologic functioning in patients compared with the mock tion (CVR; Wechsler, 1987) delayed recall was tested.
intervention and that the improvement would be detect- Testing was administered according to standardized pro-
able to caregivers reporting on patient quality of life. cedures.

Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001


4 R. N. DAVIS ET AL.

Wechsler Adult Intelligence ScaleRevised Digit Span descriptions for the anchor points of the working cat-
Forward and backward Wechsler Adult Intelligence egory were reworded slightly, and the environment cat-
ScaleRevised Digit Span (Wechsler, 1981) scores were egory was replaced with a family/caregiver category to
considered separately. Testing was administered accord- increase relevance to AD patients.
ing to standardized procedures.
Procedure
Verbal Series Attention Test Patients were recruited from the Alzheimers Disease
The Verbal Series Attention Test (VSAT; Mahurin Research Center at Baylor College of Medicine. All pa-
and Cooke, 1996) consists of a series of timed tasks, tients and caregivers provided informed consent before
including saying the alphabet, counting backward from participating in the study. Patients and their caregivers
20 by 1s, counting backward from 100 by 3s, reciting the were not informed of which condition (placebo or inter-
days of the week and months of the year in forward and vention) they would participate in first. At baseline, all
reversed order, and saying numbers and letters in alter- participants underwent a 1-hour neuropsychologic as-
nating ascending order (e.g., 1-A-2-B). sessment while their caregivers completed the QLA-P.
Examiners were blind to each patients condition (pla-
Controlled Oral Word Association Test cebo or intervention). After the baseline assessment, the
placebo group received 5 weeks of a mock intervention,
In the Controlled Oral Word Association Test (Benton
and the intervention group received 5 weeks of the cog-
and Hamsher, 1989), patients orally generated words be-
nitive intervention. After 5 weeks, all patients were re-
ginning with the letters C, F, and L in 1-minute periods.
assessed by examiners who were blind to condition. The
placebo group then crossed over to receive the 5-week
Category Fluency intervention. Four patients did not cross over to receive
In the Category Fluency test (Newcombe, 1969), pa- the intervention because of a lack of interest in continu-
tients recited as many animal names and items found in ing the study. The crossover group was then tested a third
a supermarket as they could in two separate 1-minute time after it received the intervention. (It was not pos-
intervals. sible to maintain examiner blindness to condition for the
third assessment of patients who crossed over to receive
Finger Tapping Test the intervention.) Patients who originally received the
We assessed both dominant (D) and nondominant intervention were not tested a third time.
(ND) hands using the Finger Tapping Test (Reitan and
Wolfson, 1989). It was administered according to stan- Placebo Condition (Mock Intervention)
dardized procedures. Patients in the placebo condition attended individual
weekly 1-hour clinic visits for 5 weeks. These visits con-
GDS sisted of unstructured conversation and questioning by
The GDS (Yesavage et al., 1983) is an orally admin- an examiner. Examiners asked patients about how their
istered 30-item measure of depressive symptoms. Pa- memory was doing and had patients recite overlearned
tients responded to each item by saying Yes or No. material (e.g., the alphabet, months of the year, days of
the week). Participants also watched videotapes about
Quality of Life AssessmentPatient general health issues.
The Quality of Life AssessmentPatient (QLA-P;
Blau, 1977) is a rating scale completed by caregivers to Intervention Condition
assess broad areas of patient quality of life. The original Patients in the intervention condition attended indi-
version includes 10 categories (working, leisure, eating, vidual weekly 1-hour clinic visits for 5 weeks. Addition-
sleeping, social contact, earning, parenting, loving, en- ally, they were instructed to participate in home attention
vironment, and self-acceptance). Caregivers read verbal exercises (30 minutes each day for 6 days per week)
descriptions of each category at the anchor points (0 and directed by caregivers. These exercises included a vari-
50) and rate the patients quality of life on a scale of zero ety of attention-stimulating activities (described below).
to 50, with higher scores reflecting higher quality. In the At the first clinic visit, an examiner completed a 28-item
current study, we excluded the earning and parenting interest inventory with each patient. This inventory,
categories because of a lack of relevance. The verbal which includes domains such as sports, cultural events,

Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001


COGNITIVE INTERVENTION IN AD 5

and religion, was completed to determine the patients phase, patients were shown the photograph and were
interests. These areas of interest were used to facilitate given a verbal peg to help them remember the name (e.g.,
discussion with the patient during the intervals in the knee for Naomi). In addition, they were asked to try
spaced-retrieval exercises (see below). In addition, at the to visualize the peg and associate it with the face. After
first visit, caregivers provided seven items of personal training was completed, the patients were shown the pho-
information (name, street address, city and state, zip tographs one at a time and were asked to provide the
code, age, date of birth, and telephone number) for use in name. If a patient successfully recalled all three names, a
these exercises. fourth photograph (with a new peg and name) was added
The weekly 1-hour intervention sessions began with to the initial three, and the training and subsequent test-
testing a patients recall of the seven personal items. At ing were repeated. The number of correctly recalled
the first session, 18 of the 37 patients (49%) recalled all names was recorded for each of the five intervention
seven items correctly. Consequently, these patients did sessions. It was not possible to maintain examiner blind-
not receive the spaced-retrieval intervention and started ness to condition for these data, because they were col-
immediately on the peg task described below. For the lected during the intervention session. Twenty-three of
spaced-retrieval intervention, patients were shown flash the 26 patients who completed the initial peg task were
cards with the personal information items they had been also able to complete the face-name intervention.
unable to recall initially and were asked to retrieve the The cognitive stimulation intervention consisted of a
information at expanding intervals of 5, 10, 20, 40, and series of home attention exercises intended to stimulate
60 seconds. According to Camps (1989) suggestion, the five attention levels incorporated in the Attention
when patients successfully remembered an item after the Process Training Program (Mateer and Sohlberg, 1988):
60-second interval, subsequent intervals were increased focused, sustained, selective, alternating, and divided at-
by 30 seconds up to the 3-minute maximum interval. tention. For variety and to sustain interest, six attention
When patients failed to recall an item successfully, the exercises were sent home with patients each week, with
examiner engaged the patient in casual conversation di- 1 scheduled day off per week. Some exercises focused on
rected toward his or her interests to maintain the patients physical senses (e.g., identifying smells, listening to mu-
attention. When the patient recalled an item successfully sic, describing meals), whereas others emphasized stay-
after 3 minutes, the examiner began spaced retrieval on a ing on task (e.g., card sorts, dual tasks, card games) and
subsequent item. At the conclusion of each session, the long- and short-term memory tasks (e.g., drawing a dol-
examiner again tested the patients knowledge of all lar bill, describing previously owned automobiles and
seven personal items. houses). Caregivers were asked to complete a weekly
The peg task was administered to the 18 patients who compliance sheet that recorded the time spent on each
recalled all the personal items at the outset and thus did days exercises.
not receive the spaced-retrieval intervention as well as to Complete data were obtained from 14 of the 19 care-
8 additional patients who only needed to work on one or givers of patients in the intervention group and from 8 of
two pieces of personal information in the spaced- the 14 caregivers of patients in the placebo group who
retrieval intervention and thus had time to participate in later crossed over to receive the intervention. The fre-
this next task. Patients were presented initially with three quency and quantity of participation in the at-home ex-
rhyming number-object pairs (1-bun, 2-shoe, 3-tree) ercises were nearly identical in the two groups.
and were told to use the numbers as pegs or reminders to The 22 patients with available compliance data par-
help them recall the words. If a patient recalled all three ticipated in the at-home exercises a mean of 25.59 days
pairs, a fourth pair was added (4-door). If all four pairs (of 30 total days; SD 5.57) and a mean of 11.82 hours
were recalled, a fifth pair was added, and then additional (of 15 total hours; SD 3.86).
pairs up to a maximum of 10 pairs. The maximum num-
ber of pairs that could be recalled was recorded for each RESULTS
of the five intervention sessions. The same pegs and
words were used in all sessions. Treatment Effects
After patients completed the peg task, in which they The effects of the intervention were assessed using a
had become familiar with the idea of using a word to cue series of 2 (group) 2 (time) mixed-model ANOVAs. In
another word, they were administered the face-name this approach, the presence of a significant group time
training task. In this intervention, patients attempted to interaction suggests a treatment effect. Follow-up paired
learn and recall a minimum of three staff members t tests on time 1 versus time 2 data within each group
names when shown their photographs. In the training separately were used to qualify the nature of the effect(s).

Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001


6 R. N. DAVIS ET AL.

Table 1 summarizes this set of analyses, and Table 2 TABLE 2. Means and SDs of task performance by group
reports means and SDs for all tasks by group and time. and time
As reported in Table 1, there were no significant group
Placebo (N 18) Intervention (N 19)
time interactions on any variable at the 0.05 signifi-
cance level. Marginally significant (p < 0.10) group Source Time 1 Time 2 Time 1 Time 2
time interactions did appear on three variables: Tapping Dementia severity
(D), Tapping (ND), and VSAT-seconds. Because of the MMSE 22.78 23.00 21.84 22.00
(4.45) (3.82) (4.03) (4.18)
exploratory nature of the study, we performed follow-up Verbal memory
paired t tests on time 1 versus time 2 data within each LM-IM 9.22 9.00 6.68 8.11
group to qualify the nature of these interactions. These (5.39) (6.13) (5.20) (5.79)
LM-DE 2.17 3.82 1.32 2.47
analyses revealed no significant differences between (3.28) (5.78) (2.71) (3.69)
time 1 and time 2 data within either group for Tapping Visual memory
(D) or Tapping (ND) (p > 0.10). In contrast, there was a VR-IM 13.17 17.53 14.84 17.56
(7.88) (9.65) (8.53) (6.84)
significant decrease in VSAT-seconds scores for the in- VR-DE 2.72 5.12 2.89 6.61
tervention group [t(18) 2.26; p < 0.05] but not for the (3.89) (6.91) (3.84) (9.41)
placebo group [t(17) 0.22; p > 0.10]. Attention/concentration
Digits forward 6.06 6.28 5.61 5.44
(1.66) (2.25) (1.36) (2.66)
Change Over Time Digits backward 4.83 3.67 4.83 4.17
(2.23) (2.28) (2.31) (2.38)
As shown in Table 1, there were significant increases VSATseconds 196.17 195.17 218.79 197.05
in performance from time 1 to time 2 on five measures (96.64) (101.48) (93.09) (80.21)
VSATerrors 11.11 12.11 13.79 14.79
(10.04) (11.86) (10.41) (10.99)
Word generation
TABLE 1. ANOVAs on task performance COWA 25.50 26.83 23.89 24.11
(13.07) (14.94) (11.60) (12.57)
F-ratio Animals 8.78 9.61 8.21 9.37
Degrees of (3.77) (3.88) (4.69) (5.00)
Source freedom Time Group Group time Supermarket 11.72 12.78 10.21 12.05
Dementia severity (4.20) (6.64) (4.92) (6.96)
MMSE 1,35 0.24 0.55 0.01 Motor speed
Verbal memory Tapping (D) 43.22 41.06 44.78 46.53
LM-IM 1,35 0.89 0.97 1.67 (10.45) (11.05) (7.80) (10.71)
LM-DE 1,34 6.83 0.89 0.13 Tapping (ND) 42.17 39.89 39.61 43.41
Visual memory (8.18) (9.36) (10.93) (9.40)
VR-IM 1,33 8.50 0.10 0.34 Depressive symptoms
VR-DE 1,33 7.98 0.26 0.23 GDA 5.67 5.50 4.37 4.05
Attention/concentration (7.11) (6.79) (2.27) (2.48)
Digits Forward 1,34 0.01 0.99 0.68 Quality of life
Digits Backward 1,34 1.00 1.60 1.00 QLA-P 269.94 269.71 269.17 244.41
VSATseconds 1,35 4.43 0.17 3.68* (67.94) (51.64) (51.28) (62.11)
VSATerrors 1,35 1.16 0.61 0.00
Word generation All means and SDs are based on raw scores.
COWA 1,35 0.91 0.26 0.48 MMSE, Mini-Mental State Examination; LM, Logical Memory; IM,
Animals 1,35 5.60 0.09 0.15 immediate; DE, delayed; VR, Visual Reproduction; VSAT, Verbal
Supermarket 1,35 2.79 0.43 0.21 Series Attention Test; COWA, Controlled Oral Word Association Test;
Motor speed D, dominant hand; ND, nondominant hand; GDS, Geriatric Depression
Tapping (D) 1,32 0.02 1.69 3.18* Scale; QLA-P, Quality of LifePatient.
Tapping (ND) 1,32 0.13 0.31 3.35*
Depressive symptoms
GDS 1,35 0.56 0.69 0.05
Quality of life
across both conditions. Across both intervention and pla-
QLA-P 1,32 2.88 0.40 2.10 cebo groups, patients performance improved signifi-
cantly on the variables of LM (delayed), VR (immedi-
Degrees of freedom reported less than 1,35 reflect missing data.
MMSE, Mini-Mental State Examination; LM, Logical Memory; IM, ate), VR (delayed), VSAT (seconds), and Animals.
immediate; VR, Visual Reproduction; VSAT, Verbal Series Attention
Test; COWA, Controlled Oral Word Association Test; DE, delayed; D,
dominant hand; ND, nondominant hand; GDS, Geriatric Depression Assessing the Effects of Baseline MMSE Scores on
Scale; QLA-P, Quality of LifePatient. Responses to the Intervention
*p < 0.10.
p < 0.05. Because of the variability in patients cognitive status
p < 0.01. across both groups at baseline (MMSE range: 1529), we

Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001


COGNITIVE INTERVENTION IN AD 7

conducted a series of multiple regressions that included 4.27 items of personal information (SD 1.39; range:
baseline MMSE scores, group (placebo or intervention), 26) the first time they were tested. Over the first and
and the MMSE group interaction as predictor vari- subsequent intervention sessions, the mean total number
ables. The purpose of these analyses was to test for the of items worked on in the intervention was 8.07 (SD
presence of MMSE group interactions (i.e., to assess 6.24), and the mean total number that was responded to
whether patients responded differently to the interven- correctly at the end of the sessions was 4 (SD 2.73).
tion as a function of their baseline MMSE scores). These These within-session total improvement scores differed
analyses revealed a significant MMSE group interac- significantly from zero [t(14) 5.68; p < 0.01]. Regard-
tion on only one variable, Digits Forward [F(3, 33) ing across-session data (more important than the within-
3.07; p < 0.05]. Follow-up analyses (Baron and Kenny, session results), the mean improvement from the first
1986) indicated that in patients scoring below the median intervention pretest to the last session pretest was 1.33
of baseline MMSE scores, there was a significant group items (SD 1.05), which differed significantly from
difference between placebo and intervention groups ( zero, [t(14) 4.93; p < 0.01]. Adjusting for the number
0.46; p < 0.05), with the intervention group scoring of items on which each patient was trained, patients
lower than the placebo group. learned a mean of 55% of the items they had failed
This lone and anomalous significant finding is most initially (SD 54.81).
likely spurious. Among patients who scored above the Finally, we tested across-session patient improvement
median of baseline MMSE scores, differences between on the peg and face-name tasks using paired t tests with
placebo and intervention groups were not statistically mean change scores (session 5 session 1) as dependent
significant ( 0.23; p > 0.10). variables. These analyses revealed that patient perfor-
mance on both tasks improved significantly during the
Analyses of Crossover Data intervention [t (25) 5.75; p < 0.01 and t(22)
8.35; p < 0.01, respectively]. Figure 1 displays the
Next, we tested the effects of the intervention on the
change in performance on these tasks across all five as-
crossover group using paired t tests. These analyses were
sessment sessions.
conducted on the crossover group alone, because the
original intervention group was not reassessed a third DISCUSSION
time. Using change scores (time 3 time 2) as dependent
In this study, we hypothesized that AD patients receiv-
variables, these analyses revealed a significant increase
ing face-name training, spaced retrieval, and cognitive
on only one outcome measure, Tapping (D) [t(13)
stimulation would exhibit improved recall of personal
2.17; p 0.05]. No other significant differences
information and face-name recall compared with patients
emerged in these analyses (p > 0.10). Because of con-
receiving a placebo intervention. Moreover, we hypoth-
cerns about variability in the cognitive status of cross-
esized that patients in the intervention condition would
over group patients, we performed a set of regressions
show improved neuropsychologic functioning after the
similar to those previously described, in which perfor-
intervention and that caregivers would perceive this im-
mance scores were regressed on time 2 MMSE scores,
provement as improved patient quality of life. The results
time (as a within-subject variable), and the MMSE
only modestly support our hypotheses. Patients exhibited
time interaction.
enhanced recall of personal information and face-name
These analyses revealed no significant MMSE time
recall during the 5-week intervention and improved sig-
interactions (p > 0.10). These findings suggest that the
nificantly from before to after treatment on these tasks.
crossover groups cognitive status at the outset of the
Moreover, the intervention group showed enhanced
cognitive intervention did not affect its response to the
performance on an attention/concentration task (VSAT-
intervention.
seconds), whereas the placebo groups performance re-
mained constant. The intervention group did not improve
Intervention Sessions significantly from before to after treatment, however, or
As noted previously, 18 of the 37 patients (49%) re- more than the placebo group on additional measures of
called all seven items of personal information success- dementia severity, verbal memory, visual memory, word
fully and consequently did not receive the spaced- generation, motor speed, depressive symptoms, and care-
retrieval component of the intervention. Four patients giver-rated patient quality of life. Taken together, these
refused to receive the intervention; thus, 15 patients re- findings indicate that the cognitive intervention im-
ceived the spaced-retrieval intervention. proved AD patients ability to recall personal informa-
These 15 patients successfully recalled an average of tion and face-name associations. These gains failed to

Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001


8 R. N. DAVIS ET AL.

intervention group and were not predicted, they likely


reflect small practice effects on these measures.
The finding of AD patients improvement on tests of
personal information and face-name recall are consistent
with previous studies of spaced-retrieval interventions
(Abrahams and Camp, 1993; Camp et al., 1996; Camp
and Stevens, 1990; McKitrick et al., 1992). On the other
hand, the current study differs from these previous in-
vestigations in its inclusion of a carefully chosen set of
neuropsychologic outcome measures as well as a ran-
domized placebo-controlled design with blinded assess-
ments. In addition, our groups were sufficiently compa-
rable on major variables such as age, gender, depression,
baseline MMSE scores, and years of education. Our find-
ings suggest that whereas spaced-retrieval may be quite
useful for helping AD patients remember personal infor-
mation over longer periods of time, the method (in con-
junction with face-name training and cognitive stimula-
tion) does not seem to yield generalized improvement on
memory or other neuropsychologic tasks. Nonetheless, our
replication of several previously successful spaced-retrieval
interventions is encouraging, as AD patients did demon-
strate improved retention of at least some information.
The present findings are partly consistent with previ-
ous studies of cognitive stimulation. As noted earlier,
whereas some studies of cognitive stimulation have
yielded positive results (Breuil et al., 1994; Quayhagen
et al., 1995), interpretation of these results has been im-
peded by methodological problems. Our cognitive inter-
vention did not lead to improvement on the MMSE, a
result that one cognitive stimulation intervention did pro-
duce (Breuil et al., 1994). The current studys failure to
FIG. 1. Improvement on peg memory and face-name recall tasks dur- replicate this effect may imply that specific cognitive
ing the intervention. (A) Peg memory task. (B) Face-name recall task.
stimulation techniques conducted by trained profession-
als (as in the study by Breuil et al, 1994) are more ef-
generalize to psychometric improvement and quality of fective at increasing global cognitive functioning than
life improvement, however, as detected by caregivers. cognitive stimulation exercises overseen by caregivers
This finding is consistent with previous studies (Camp et combined with face-name training and spaced retrieval.
al., 1996), in which AD patients overall cognitive func- Differences in the implementation of cognitive stimula-
tioning declined over time even as they showed improve- tion across studies may also partly account for this dis-
ment on domain-specific memory tasks after spaced- crepancy. A true test of this hypothesis would require a
retrieval interventions. Moreover, in another study, AD comparative treatment outcome study on comparable
patients exhibited improved name-face recall but only groups of AD patients, however.
slight evidence of generalized improvement (Kesslak et The present study has some potential limitations. First,
al., 1997). we cannot clearly separate the contributions of the
Across both conditions, patients improved from before spaced-retrieval intervention from the contributions of
to after treatment on measures of verbal memory (LM- face-name training or the cognitive stimulation exercises.
D), visual memory (VR-IM, VR-D), attention/concen- It is therefore not clear if an increased emphasis on one
tration (VSAT-seconds), and category fluency (Ani- component or the other would have improved patients
mals). The crossover groups performance also improved functioning to a greater extent. Second, we relied on a
on one measure of motor speed (Tapping-D) relative to sample of AD patients who varied considerably in their
its baseline. Because these effects are not specific to the cognitive status at baseline. Our results indicate that this

Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001


COGNITIVE INTERVENTION IN AD 9

variability did not affect patients responses to the inter- Breuil V, De Rotrou J, Forette F, et al. Cognitive stimulation of patients
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Acknowledgments. This research was supported by grants Quayhagen MP, Quayhagen M, Corbeil R, et al. A dyadic remediation
from the Methodist Hospital Foundation and the Harry and program for care recipients with dementia. Nurs Res 1995;44:1539.
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Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001