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

1
2 R. N. DAVIS ET AL.
tion by recalling that information over increasingly
longer periods. In this approach, patients are taught some
information and then repeatedly tested on it over time.
When a successful retrieval is made, the interval preced-
ing the next recall test increases. When a retrieval failure
occurs, the patient is given the correct response and
asked to repeat it.
Spaced-retrieval interventions have been found to im-
prove retention of names of common objects (Abrahams
and Camp, 1993), face-name associations (Camp and
Stevens, 1990), object-location associations (Camp and
Stevens, 1990), and performance on a prospective
memory task (Camp et al., 1996; McKitrick et al., 1992)
among patients with AD. Interventions using spaced re-
trieval may be advantageous for AD patients because
they seem to require little cognitive effort (Camp and
Stevens, 1990). Moreover, there is some evidence that
the spaced-retrieval method relies on implicit memory
(Camp et al., 1996), that is, knowledge expressed in per-
formance that does not require conscious awareness
(Schachter et al., 1988), which seems to be relatively
intact in AD (Maki, 1995).
Although spaced retrieval seems to be a promising
intervention for memory decline in AD, virtually all
studies of its efficacy have used small (n < 10) sample
sizes, have not used control groups, have not randomly
assigned patients to conditions, and have not used asses-
sors blind to condition. Moreover, it is unclear if pa-
tients gains after spaced-retrieval interventions general-
ize to psychometric improvement or improvement in
quality of life.
Second, some cognitive stimulation programs have
demonstrated efficacy among patients with AD (Breuil et
al., 1994; Quayhagen et al., 1995). For example, Quay-
hagen et al. (1995) randomly assigned 78 family dyads
(one AD patient plus one family caregiver) to active
cognitive stimulation, passive cognitive stimulation, or a
wait-list control group. All families in the treatment
groups received weekly training visits by members of the
research team, who trained patients and their caregivers
to implement various cognitively stimulating activities.
Active cognitive stimulation occurred daily for 60 min-
utes 6 days per week across 12 weeks and consisted of
memory, problem-solving, and conversation activities.
Passive cognitive stimulation differed from active cog-
nitive stimulation only in that the patient was exposed to
passive observation of the activity without enforced par-
ticipation.
After the intervention, patients receiving active stimu-
lation exhibited improvement in overall cognitive func-
tioning on the Mattis Dementia Rating Scale (Mattis,
Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001
1988) and on a composite measure of word fluency. In
contrast, patients receiving passive stimulation and wait-
list controls declined on these measures. Moreover, pa-
tients in both treatment conditions improved slightly on
a composite measure of nonverbal memory, whereas the
control group declined on this measure. Patients in both
treatment conditions also exhibited fewer behavioral
problems compared with the patients in the control
group. No significant differences were found among
groups on measures of problem solving or verbal
memory. After 9 months of follow-up without continued
intervention, the original active group returned to base-
line on those measures it had improved on after treat-
ment, whereas the other two groups fell below baseline
on almost all measures (Quayhagen et al., 1995).
Although these results are encouraging, they are some-
what difficult to interpret for two reasons. First, the au-
thors used composite scores derived from several mea-
sures of each outcome domain. For example, scores on
the memory factor of the Mattis Dementia Rating Scale
were aggregated with scores on Logical Memory (LM) I,
Figural Memory, and Visual Reproduction (VR) from
the Wechsler Memory ScaleRevised (WMS-R; Wech-
sler, 1987), from which a memory composite score
was calculated. The psychometric properties of these
composite scores are unknown, and no precedent ex-
ists for aggregating these scores in such a manner. More-
over, it is not clear on which specific measure(s), if any,
the groups differed. Second, the authors report only the
results of their omnibus F-tests (group time) but no
follow-up test results. It is therefore impossible to deter-
mine which groups, if any, differed from one another at
each time point (before treatment, after treatment, and at
9-month follow-up).
In another test of the efficacy of cognitive stimulation,
56 patients with dementia (not necessarily AD) were
randomly assigned to receive either 10 cognitive stimu-
lation sessions over 5 weeks or no treatment (Breuil et
al., 1994). Cognitive stimulation sessions relied strongly
on mental imagery to stimulate encoding, consolidation,
and retrieval of information. At follow-up, the interven-
tion group had significantly higher scores on the Mini-
Mental State Examination (MMSE; Folstein et al., 1975)
and marginally significant improvement on word list
memory from the Consortium to Establish a Registry for
Alzheimers Disease battery (Morris et al., 1989). Pa-
tients in the intervention group improved an average of
1.4 points on the MMSE and 1.1 points on word list
memory from before to after treatment. No significant
differences emerged on a measure of verbal fluency, and
scores on five other measures were not analyzed because
of ceiling or floor effects.
 COGNITIVE INTERVENTION IN AD
Training in face-name associations has also demon-
strated effectiveness for AD patients (Kesslak et al.,
1997). In one study, 11 AD patients and their relatives
(who served as controls) participated in a 4-week inter-
vention targeting face-name recall. Patients and their
relatives were seen as a group and received instruction in
strategies for face-name rehearsal. Photographs were
taken of each group member, and participants practiced
recalling each group members name when shown a pho-
tograph. To facilitate face-name identification, each
group member discussed his or her interests, family, and
background in the groups presence to facilitate deep
processing. This intervention yielded significant im-
provement in face-name recall among AD patients as
well as improvement on the Geriatric Depression Scale
(GDS; Yesavage et al., 1983) and a digit copying task
(Kesslak et al., 1997). Another intervention that used
face-name rehearsal among AD patients also yielded im-
proved face-name recall using highly similar procedures
(Sandman, 1993).
Although cognitive stimulation and face-name train-
ing seem to be promising interventions for memory de-
cline in AD, most studies conducted thus far have not
included adequate measures of neuropsychologic func-
tioning and/or patient quality of life. In some cases, even
when psychometric improvement is detected, it remains
unclear as to whether the changes are detectable to care-
givers or actually influence the patients daily function-
ing. Moreover, as noted previously, the outcome mea-
sures used in some of these studies have been difficult to
interpret.
In the current study, we sought to conduct a rigorous
test of a cognitive intervention that included the most
promising cognitive interventions for AD patients ac-
cording to past literature: face-name training, spaced re-
trieval, and cognitive stimulation. We included measures
of face-name recall and recall of personal information as
well as a battery of neuropsychologic tests (administered
by examiners blind to treatment condition) and a care-
giver rating scale to assess patient quality of life. Patients
with AD were randomly assigned to receive either the
cognitive intervention or a mock (placebo) intervention.
The placebo group crossed over to receive the interven-
tion after the original intervention group had been
treated. Based on previous findings, we hypothesized
that patients would exhibit enhanced face-name recall
and recall of personal information after receiving the
cognitive intervention. Furthermore, we hypothesized
that the cognitive intervention would improve neuropsy-
chologic functioning in patients compared with the mock
intervention and that the improvement would be detect-
able to caregivers reporting on patient quality of life.
3
SUBJECTS AND METHODS
Participants
Thirty-seven patients (16 men, 21 women) partici-
pated in the study. All patients were diagnosed with
probable AD by National Institute of Neurological Com-
municative Disorders and StrokeAlzheimers Disease
and Related Disorders Association criteria (McKhann et
al., 1984). The patients were randomly assigned to one of
two groups: a 5-week intervention group or a 5-week
placebo group. The placebo group (6 men, 12 women)
had a mean educational level of 12.97 years (SD 2.56)
and a mean age of 72.56 years (SD 7.62). The inter-
vention group (10 men, 9 women) had a mean educa-
tional level of 15.06 years (SD 3.86) and a mean age
of 68.67 years (SD 3.86). At baseline, the placebo
group had a mean MMSE score of 22.78 (SD 4.45),
and the intervention group had a mean MMSE score of
21.84 (SD 4.03). Both groups scored within the nor-
mal range on the GDS: the placebo group had a mean
score of 5.67 (SD 7.11), and the intervention group
had a mean score of 4.37 (SD 2.27). None of these
minor group differences was statistically significant.
Regarding medication use, five patients in the inter-
vention group and four patients in the placebo group
were taking anti-dementia medication (donapezil [Ari-
cept; Pfizer] or tacrine [Cognex; Parke-Davis]). Five pa-
tients in the intervention group and two patients in the
placebo group were taking antidepressant medication,
mainly fluoxetine (Prozac; Eli Lilly and Co.) or sertraline
(Zoloft; Roerig).
Finally, two patients in each group were taking minor
tranquilizers. The relative frequencies of patients taking
these various medications did not differ significantly be-
tween the intervention and placebo groups.
Materials
MMSE
The MMSE (Folstein et al., 1975) is a 30-item assess-
ment of cognitive status. It was administered according
to standardized procedures.
WMS-R Logical Memory
Immediate and 30-minute WMS-R Logical Memory
(CLM; Wechsler, 1987) delayed recall was tested. Test-
ing was administered according to standardized proce-
dures.
WMS-R Visual Reproduction
Immediate and 30-minute WMS-R Visual Reproduc-
tion (CVR; Wechsler, 1987) delayed recall was tested.
Testing was administered according to standardized pro-
cedures.
Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001
4 R. N. DAVIS ET AL.
Wechsler Adult Intelligence ScaleRevised Digit Span
Forward and backward Wechsler Adult Intelligence
ScaleRevised Digit Span (Wechsler, 1981) scores were
considered separately. Testing was administered accord-
ing to standardized procedures.
Verbal Series Attention Test
The Verbal Series Attention Test (VSAT; Mahurin
and Cooke, 1996) consists of a series of timed tasks,
including saying the alphabet, counting backward from
20 by 1s, counting backward from 100 by 3s, reciting the
days of the week and months of the year in forward and
reversed order, and saying numbers and letters in alter-
nating ascending order (e.g., 1-A-2-B).
Controlled Oral Word Association Test
In the Controlled Oral Word Association Test (Benton
and Hamsher, 1989), patients orally generated words be-
ginning with the letters C, F, and L in 1-minute periods.
Category Fluency
In the Category Fluency test (Newcombe, 1969), pa-
tients recited as many animal names and items found in
a supermarket as they could in two separate 1-minute
intervals.
Finger Tapping Test
We assessed both dominant (D) and nondominant
(ND) hands using the Finger Tapping Test (Reitan and
Wolfson, 1989). It was administered according to stan-
dardized procedures.
GDS
The GDS (Yesavage et al., 1983) is an orally admin-
istered 30-item measure of depressive symptoms. Pa-
tients responded to each item by saying Yes or No.
Quality of Life AssessmentPatient
The Quality of Life AssessmentPatient (QLA-P;
Blau, 1977) is a rating scale completed by caregivers to
assess broad areas of patient quality of life. The original
version includes 10 categories (working, leisure, eating,
sleeping, social contact, earning, parenting, loving, en-
vironment, and self-acceptance). Caregivers read verbal
descriptions of each category at the anchor points (0 and
50) and rate the patients quality of life on a scale of zero
to 50, with higher scores reflecting higher quality. In the
current study, we excluded the earning and parenting
categories because of a lack of relevance. The verbal
Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001
descriptions for the anchor points of the working cat-
egory were reworded slightly, and the environment cat-
egory was replaced with a family/caregiver category to
increase relevance to AD patients.
Procedure
Patients were recruited from the Alzheimers Disease
Research Center at Baylor College of Medicine. All pa-
tients and caregivers provided informed consent before
participating in the study. Patients and their caregivers
were not informed of which condition (placebo or inter-
vention) they would participate in first. At baseline, all
participants underwent a 1-hour neuropsychologic as-
sessment while their caregivers completed the QLA-P.
Examiners were blind to each patients condition (pla-
cebo or intervention). After the baseline assessment, the
placebo group received 5 weeks of a mock intervention,
and the intervention group received 5 weeks of the cog-
nitive intervention. After 5 weeks, all patients were re-
assessed by examiners who were blind to condition. The
placebo group then crossed over to receive the 5-week
intervention. Four patients did not cross over to receive
the intervention because of a lack of interest in continu-
ing the study. The crossover group was then tested a third
time after it received the intervention. (It was not pos-
sible to maintain examiner blindness to condition for the
third assessment of patients who crossed over to receive
the intervention.) Patients who originally received the
intervention were not tested a third time.
Placebo Condition (Mock Intervention)
Patients in the placebo condition attended individual
weekly 1-hour clinic visits for 5 weeks. These visits con-
sisted of unstructured conversation and questioning by
an examiner. Examiners asked patients about how their
memory was doing and had patients recite overlearned
material (e.g., the alphabet, months of the year, days of
the week). Participants also watched videotapes about
general health issues.
Intervention Condition
Patients in the intervention condition attended indi-
vidual weekly 1-hour clinic visits for 5 weeks. Addition-
ally, they were instructed to participate in home attention
exercises (30 minutes each day for 6 days per week)
directed by caregivers. These exercises included a vari-
ety of attention-stimulating activities (described below).
At the first clinic visit, an examiner completed a 28-item
interest inventory with each patient. This inventory,
which includes domains such as sports, cultural events,
 COGNITIVE INTERVENTION IN AD
and religion, was completed to determine the patients
interests. These areas of interest were used to facilitate
discussion with the patient during the intervals in the
spaced-retrieval exercises (see below). In addition, at the
first visit, caregivers provided seven items of personal
information (name, street address, city and state, zip
code, age, date of birth, and telephone number) for use in
these exercises.
The weekly 1-hour intervention sessions began with
testing a patients recall of the seven personal items. At
the first session, 18 of the 37 patients (49%) recalled all
seven items correctly. Consequently, these patients did
not receive the spaced-retrieval intervention and started
immediately on the peg task described below. For the
spaced-retrieval intervention, patients were shown flash
cards with the personal information items they had been
unable to recall initially and were asked to retrieve the
information at expanding intervals of 5, 10, 20, 40, and
60 seconds. According to Camps (1989) suggestion,
when patients successfully remembered an item after the
60-second interval, subsequent intervals were increased
by 30 seconds up to the 3-minute maximum interval.
When patients failed to recall an item successfully, the
examiner engaged the patient in casual conversation di-
rected toward his or her interests to maintain the patients
attention. When the patient recalled an item successfully
after 3 minutes, the examiner began spaced retrieval on a
subsequent item. At the conclusion of each session, the
examiner again tested the patients knowledge of all
seven personal items.
The peg task was administered to the 18 patients who
recalled all the personal items at the outset and thus did
not receive the spaced-retrieval intervention as well as to
8 additional patients who only needed to work on one or
two pieces of personal information in the spaced-
retrieval intervention and thus had time to participate in
this next task. Patients were presented initially with three
rhyming number-object pairs (1-bun, 2-shoe, 3-tree)
and were told to use the numbers as pegs or reminders to
help them recall the words. If a patient recalled all three
pairs, a fourth pair was added (4-door). If all four pairs
were recalled, a fifth pair was added, and then additional
pairs up to a maximum of 10 pairs. The maximum num-
ber of pairs that could be recalled was recorded for each
of the five intervention sessions. The same pegs and
words were used in all sessions.
After patients completed the peg task, in which they
had become familiar with the idea of using a word to cue
another word, they were administered the face-name
training task. In this intervention, patients attempted to
learn and recall a minimum of three staff members
names when shown their photographs. In the training
5
phase, patients were shown the photograph and were
given a verbal peg to help them remember the name (e.g.,
knee for Naomi). In addition, they were asked to try
to visualize the peg and associate it with the face. After
training was completed, the patients were shown the pho-
tographs one at a time and were asked to provide the
name. If a patient successfully recalled all three names, a
fourth photograph (with a new peg and name) was added
to the initial three, and the training and subsequent test-
ing were repeated. The number of correctly recalled
names was recorded for each of the five intervention
sessions. It was not possible to maintain examiner blind-
ness to condition for these data, because they were col-
lected during the intervention session. Twenty-three of
the 26 patients who completed the initial peg task were
also able to complete the face-name intervention.
The cognitive stimulation intervention consisted of a
series of home attention exercises intended to stimulate
the five attention levels incorporated in the Attention
Process Training Program (Mateer and Sohlberg, 1988):
focused, sustained, selective, alternating, and divided at-
tention. For variety and to sustain interest, six attention
exercises were sent home with patients each week, with
1 scheduled day off per week. Some exercises focused on
physical senses (e.g., identifying smells, listening to mu-
sic, describing meals), whereas others emphasized stay-
ing on task (e.g., card sorts, dual tasks, card games) and
long- and short-term memory tasks (e.g., drawing a dol-
lar bill, describing previously owned automobiles and
houses). Caregivers were asked to complete a weekly
compliance sheet that recorded the time spent on each
days exercises.
Complete data were obtained from 14 of the 19 care-
givers of patients in the intervention group and from 8 of
the 14 caregivers of patients in the placebo group who
later crossed over to receive the intervention. The fre-
quency and quantity of participation in the at-home ex-
ercises were nearly identical in the two groups.
The 22 patients with available compliance data par-
ticipated in the at-home exercises a mean of 25.59 days
(of 30 total days; SD 5.57) and a mean of 11.82 hours
(of 15 total hours; SD 3.86).
RESULTS
Treatment Effects
The effects of the intervention were assessed using a
series of 2 (group) 2 (time) mixed-model ANOVAs. In
this approach, the presence of a significant group time
interaction suggests a treatment effect. Follow-up paired
t tests on time 1 versus time 2 data within each group
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
conducted a series of multiple regressions that included
baseline MMSE scores, group (placebo or intervention),
and the MMSE group interaction as predictor vari-
ables. The purpose of these analyses was to test for the
presence of MMSE group interactions (i.e., to assess
whether patients responded differently to the interven-
tion as a function of their baseline MMSE scores). These
analyses revealed a significant MMSE group interac-
tion on only one variable, Digits Forward [F(3, 33)
3.07; p < 0.05]. Follow-up analyses (Baron and Kenny,
1986) indicated that in patients scoring below the median
of baseline MMSE scores, there was a significant group
difference between placebo and intervention groups (
0.46; p < 0.05), with the intervention group scoring
lower than the placebo group.
This lone and anomalous significant finding is most
likely spurious. Among patients who scored above the
median of baseline MMSE scores, differences between
placebo and intervention groups were not statistically
significant ( 0.23; p > 0.10).
Analyses of Crossover Data
Next, we tested the effects of the intervention on the
crossover group using paired t tests. These analyses were
conducted on the crossover group alone, because the
original intervention group was not reassessed a third
time. Using change scores (time 3 time 2) as dependent
variables, these analyses revealed a significant increase
on only one outcome measure, Tapping (D) [t(13)
2.17; p 0.05]. No other significant differences
emerged in these analyses (p > 0.10). Because of con-
cerns about variability in the cognitive status of cross-
over group patients, we performed a set of regressions
similar to those previously described, in which perfor-
mance scores were regressed on time 2 MMSE scores,
time (as a within-subject variable), and the MMSE
time interaction.
These analyses revealed no significant MMSE time
interactions (p > 0.10). These findings suggest that the
crossover groups cognitive status at the outset of the
cognitive intervention did not affect its response to the
intervention.
Intervention Sessions
As noted previously, 18 of the 37 patients (49%) re-
called all seven items of personal information success-
fully and consequently did not receive the spaced-
retrieval component of the intervention. Four patients
refused to receive the intervention; thus, 15 patients re-
ceived the spaced-retrieval intervention.
These 15 patients successfully recalled an average of
7
4.27 items of personal information (SD 1.39; range:
26) the first time they were tested. Over the first and
subsequent intervention sessions, the mean total number
of items worked on in the intervention was 8.07 (SD
6.24), and the mean total number that was responded to
correctly at the end of the sessions was 4 (SD 2.73).
These within-session total improvement scores differed
significantly from zero [t(14) 5.68; p < 0.01]. Regard-
ing across-session data (more important than the within-
session results), the mean improvement from the first
intervention pretest to the last session pretest was 1.33
items (SD 1.05), which differed significantly from
zero, [t(14) 4.93; p < 0.01]. Adjusting for the number
of items on which each patient was trained, patients
learned a mean of 55% of the items they had failed
initially (SD 54.81).
Finally, we tested across-session patient improvement
on the peg and face-name tasks using paired t tests with
mean change scores (session 5 session 1) as dependent
variables. These analyses revealed that patient perfor-
mance on both tasks improved significantly during the
intervention [t (25) 5.75; p < 0.01 and t(22)
8.35; p < 0.01, respectively]. Figure 1 displays the
change in performance on these tasks across all five as-
sessment sessions.
DISCUSSION
In this study, we hypothesized that AD patients receiv-
ing face-name training, spaced retrieval, and cognitive
stimulation would exhibit improved recall of personal
information and face-name recall compared with patients
receiving a placebo intervention. Moreover, we hypoth-
esized that patients in the intervention condition would
show improved neuropsychologic functioning after the
intervention and that caregivers would perceive this im-
provement as improved patient quality of life. The results
only modestly support our hypotheses. Patients exhibited
enhanced recall of personal information and face-name
recall during the 5-week intervention and improved sig-
nificantly from before to after treatment on these tasks.
Moreover, the intervention group showed enhanced
performance on an attention/concentration task (VSAT-
seconds), whereas the placebo groups performance re-
mained constant. The intervention group did not improve
significantly from before to after treatment, however, or
more than the placebo group on additional measures of
dementia severity, verbal memory, visual memory, word
generation, motor speed, depressive symptoms, and care-
giver-rated patient quality of life. Taken together, these
findings indicate that the cognitive intervention im-
proved AD patients ability to recall personal informa-
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.
FIG. 1. Improvement on peg memory and face-name recall tasks dur-
ing the intervention. (A) Peg memory task. (B) Face-name recall task.
generalize to psychometric improvement and quality of
life improvement, however, as detected by caregivers.
This finding is consistent with previous studies (Camp et
al., 1996), in which AD patients overall cognitive func-
tioning declined over time even as they showed improve-
ment on domain-specific memory tasks after spaced-
retrieval interventions. Moreover, in another study, AD
patients exhibited improved name-face recall but only
slight evidence of generalized improvement (Kesslak et
al., 1997).
Across both conditions, patients improved from before
to after treatment on measures of verbal memory (LM-
D), visual memory (VR-IM, VR-D), attention/concen-
tration (VSAT-seconds), and category fluency (Ani-
mals). The crossover groups performance also improved
on one measure of motor speed (Tapping-D) relative to
its baseline. Because these effects are not specific to the
Alzheimer Disease and Associated Disorders, Vol. 15, No. 1, 2001
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
replicate this effect may imply that specific cognitive
stimulation techniques conducted by trained profession-
als (as in the study by Breuil et al, 1994) are more ef-
fective at increasing global cognitive functioning than
cognitive stimulation exercises overseen by caregivers
combined with face-name training and spaced retrieval.
Differences in the implementation of cognitive stimula-
tion across studies may also partly account for this dis-
crepancy. A true test of this hypothesis would require a
comparative treatment outcome study on comparable
groups of AD patients, however.
The present study has some potential limitations. First,
we cannot clearly separate the contributions of the
spaced-retrieval intervention from the contributions of
face-name training or the cognitive stimulation exercises.
It is therefore not clear if an increased emphasis on one
component or the other would have improved patients
functioning to a greater extent. Second, we relied on a
sample of AD patients who varied considerably in their
cognitive status at baseline. Our results indicate that this
 COGNITIVE INTERVENTION IN AD
variability did not affect patients responses to the inter-
vention, however. Third, it might be argued that our in-
tervention was not powerful enough to produce the de-
sired level of change. This criticism is largely untenable
when the burden placed on patients and caregivers that
participate in these studies is considered. The sessions
required transportation, an available caregiver, and the
caregivers willingness to stimulate the patient 6 days per
week for 5 weeks. Moreover, the duration of the inter-
vention falls within the accepted standard duration for
memory training methods (Yesavage, 1985) and is com-
parable to that of previous interventions of the same type
(Breuil et al., 1994). Finally, we do not know how long
the gains experienced by patients for learning personal
information and names would have persisted had they
continued to practice the intervention.
In the absence of pharmacologic interventions, it is
clear that the progressive neural degeneration in AD ex-
ceeds the capacity of the central nervous system to com-
pensate for the neuroanatomic changes and resulting
functional deficits. Clearly, there are limits on what may
be reasonably expected of a cognitive intervention in
unmedicated AD patients. With the advent of new symp-
tomatic pharmacologic interventions (Rogers et al.,
1998), however, cognitive interventions that stimulate
neural functioning may become increasingly effective
(Kesslak et al., 1997). It remains to be determined if
adding a cognitive intervention to drug treatment en-
hances patient functioning over drug treatment alone.
Given the improvements exhibited on some tasks by AD
patients after cognitive interventions, studies of combi-
nation (drug plus cognitive intervention) treatments are
likely to constitute a worthy and timely endeavor over
the next few years.
Acknowledgments. This research was supported by grants
from the Methodist Hospital Foundation and the Harry and
Isabel Cameron Foundation to Rachelle S. Doody, M.D., Ph.D.
Drs. Doody and Massman also received support from NIH
grant AGO8664.
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