Age and Ageing 1996.25:209-21 3
Cognitive Decline in Patients with
Alzheimer's Disease, Vascular Dementia and
Senile Dementia of Lewy Body Type
C. BALLARD, A. PATEL, F. OYEBODE, G. WILCOCK
Summary
One hundred and twenty-four patients with DSM-III-R dementia were assessed with a standardized battery
which included the Geriatric Mental State Schedule, the History and Aetiology Schedule, the Secondary
Dementia Schedule and the CAMCOG. Eighty-nine patients were followed up for 1 year, 76 of whom
completed a repeat CAMCOG. Patients with Alzheimer's disease, vascular dementia and senile dementia of
Lewy body type (SDLT) all had a similar degree of cognitive impairment at the time of the baseline interview.
Patients with Alzheimer's disease and vascular dementia each experienced a mean decline of 13 points on the
CAMCOG in 1 year compared with a mean decline of 27 points in patients with S D L T . Patients with S D L T
had a significantly greater decline of verbal fluency than both the other groups. Women were significantly more
impaired than men at the time of the baseline assessment but experienced a similar decline during the year of
follow-up.
Introduction
Cognitive decline is an integral part of Alzheimer's
disease. A patient may be expected to deteriorate by 3 to
4 points on a Mini-Mental State Examination [1] or
approximately 12 points on a CAMCOG schedule [2]
annually. There has been some suggestion that patients
with mild impairment decline at a faster rate [3-5] and
that women with Alzheimer's disease have worse
cognitive functioning than men with a comparable
duration of illness [6], although other studies have been
unable to confirm these findings [2]. Early onset of
Alzheimer's disease has also been suggested as a factor
related to more rapid cognitive decline, with a two-fold
difference evident between patients aged under- and
over-65 years [7], although other reports have not
found a significant association [2]. The presence of
extrapyramidal symptoms was linked to more severe
cognitive impairment in one report [8]. Samples have
generally been small and the sample origins have
differed between studies and this may partially explain
some of the discrepancies.
Less attention has been focused upon vascular
dementia. Almkvist [9] has reviewed the literature
comparing patients with vascular dementia and Alzheimer's disease. Controlling for the duration of illness,
there appears to be no difference in the overall severity
of cognitive impairment but patients with vascular
dementia tend to have slower reaction times, more
impaired verbal fluency and more difficulties with
planning tasks. Senile dementia of Lewy Body type
(SDLT) has received little attention but planning tasks
have been found to be particularly severely impaired
[10] and neuropathological studies have reported
hippocampal sparing [11]. Treatment trials involving
patients with vascular dementia have suggested an
annual decline of approximately 4% on formal tests of
cognitive function [12]. The rate of progression of
S D L T is unknown.
This study reports the results of a CAMCOG
assessment of a sample of dementia patients in contact
with clinical services at baseline and after 1 year of
follow-up.
Methods
The case notes of consecutive referrals to four old-age
psychiatry services in the West Midlands and a Memory
Clinic in Bristol were reviewed. All patients aged 65 years or
over who fulfilled the CAM DEX criteria for mild or moderate
dementia [13] and had an informant in contact at least once a
week were selected. All those who fulfilled the entry criteria
were contacted together with their carer and asked if they
would like to participate in the study. This procedure
continued from April 1993 until the target number of patients
had been recruited in December 1993. A comprehensive
assessment was completed which included a Geriatric Mental
State Schedule [14] and History and Aetiology Schedule [15].
Cognitive function was assessed using the CAMCOG
schedule [13]. The total score was identified as well as the
scores on each of the sub-sections [16]—orientation, comprehension, expression, praxis, recent memory, visual
C. BALLARD ET AL.
memory, remote memory, attention and calculation, perception (agnosia), verbal fluency and abstract thinking.
Information regarding a range of potential associations
including deafness, education and the age of onset of the
dementia was obtained from the History and Aetiology
Schedule [15]. Depression was assessed using the Cornell
Depression Scale [17] and psychotic symptoms were assessed
using the Burns Symptom Checklist [18].
Dementia was diagnosed according the NINCDS ADRDA
[19], DSM-III-R [20], the Hachinski scale [21], criteria for
SDLT [22] and the HAS AGECAT [15]. The method of
application is described elsewhere [18].
One year after the initial interview, each patient was
re-interviewed and the CAMCOG schedule was again
administered. The sub-scales were derived in the same
manner as described for the initial interviews.
Descriptive data are reported including the mean baseline
total CAMCOG scores. These scores were compared between
patients with the different dementias using the MannWhitney U test. A stepwise logistic regression analysis [23]
was used to compare the CAMCOG sub-scores between
patients with Alzheimer's disease and vascular dementia,
Alzheimer's disease and SDLT, and vascular dementia and
SDLT, respectively. In addition, a linear regression analysis
was undertaken to explore the association of total CAMCOG
scores and a range of demographic factors including sex, age,
age at onset, Cornell Depression Score, deafness, number of
years of education and the presence of psychotic symptoms.
Spearman's rank correlation coefficients between each of the
CAMCOG sub-scores and the overall CAMCOG score were
included. These were calculated separately for patients with
Alzheimer's disease, vascular dementia, and SDLT.
The number of points of deterioration on the total
CAMCOG score at 1 year's follow-up is described for
patients with Alzheimer's disease, vascular dementia and
SDLT. The magnitude of deterioration between the different
dementias was compared using the Mann-Whitney U test.
The magnitude of deterioration over 1 year was also evaluated
using a linear regression analysis with sex, age, age at onset,
Cornell Depression Scores, deafness, number of years of
education and psychotic symptoms as the independent
variables. Deterioration in each of the CAMCOG subscores
was compared between patients with Alzheimer's disease and
vascular dementia and between men and women using logistic
regression analysis.
Results
Of the patients approached, 90.4% agreed to participate
in the study. Of the 125 participants, 124 fulfilled the
DSM-III-R criteria for dementia. The mean age of the
subjects was 79.6 years, 91 were women and 33 men.
Two were inpatients, 39 day patients and the remainder
outpatients. Fifty-five patients had probable Alzheimer's disease, 33 possible Alzheimer's disease, 20
vascular dementia and 12 S D L T . Four patients fulfilled
the DSM-III-R criteria for dementia but could not be
classified further. One hundred and sixteen patients
completed a baseline CAMCOG assessment. Six had
impaired vision and two were unco-operative.
Eighty-nine patients completed the year of followup. Twenty-one patients died during the course of the
study, four moved to different areas, five dropped out
and the follow-up information was incomplete for five
patients. Seventy-six of the 89 patients had repeated
CAMCOG assessments at 1 year, seven patients were
unable to complete the repeat CAMCOG because of
poor eyesight and six were unco-operative. Twentyeight of the patients not completing follow-up had
Alzheimer's disease, five had vascular dementia and
three had S D L T . Their mean baseline CAMCOG
score was 38.58 (Alzheimer's disease mean 39.4,
vascular dementia mean 39.2, S D L T mean 30.0).
Fifty-three of the patients completing the repeat
cognitive testing suffered from Alzheimer's disease,
Table I. Comparing the baseline cognitive assessments between patients with the different dementias using a logistic regression
analysis, Wald statistics and probability (p) values
Alzheimer's disease vs.
vascular dementia
Alzheimer's disease vs.
senile dementia of
Lewy body type
Vascular dementia vs.
senile dementia of
Lewy body type
CAMCOG score
Wald
P
Wald
P
Wald
P
Total
Orientation
Comprehension
Expression
Praxis
Recent memory
Visual memory
Remote memory
Attention and calculation
Perception (agnosia)
Abstract thinking
Verbal fluency
0.19
0.46
2.01
0.25
1.27
5.30
7.94
0.73
0.43
1.89
1.15
0.22
0.66
0.50
0.16
0.62
0.26
0.02*
0.005*
0.39
0.51
0.17
0.28
0.64
0.22
2.10
0.11
0.79
0.55
5.41
0.18
1.82
0.10
0.45
0.18
0.03
0.64
0.15
0.74
0.37
0.46
0.02*
0.67
0.18
0.75
0.50
0.67
0.85
1.51
0.82
1.56
1.29
0.40
0.05
4.18
2.09
0.33
0.20
0.01
0.26
0.22
0.37
0.21
0.26
0.53
0.82
0.04
0.15
0.57
0.66
0.93
0.61
•p < 0.05.
COGNITIVE DECLINE IN THREE TYPES OF DEMENTIA
Table II. A linear regression analysis of variables associated
with the severity of cognitive impairment: T-values and
probability (p)
Table IV. Linear regression analysis of variables associated
with the magnitude of cognitive decline over 1 year: t statistic
and p values
Variable
Variables
Female sex
Age at onset of dementia
Age of patient at assessment
Cornell depression score
Deafness
Number of years of education
One or more psychotic symptom
2.47
0.07
-0.63
0.28
0.43
-0.51
-0.75
0.01»
0.94
0.53
0.78
0.67
0.96
0.45
Female sex
Age of onset of dementia
Age of patient at assessment
Cornell depression score
Deafness
Number of years of education
One or more psychotic symptom
0.11
0.53
0.12
0.24
0.03
0.76
-0.83
0.89
0.59
0.91
0.81
0.93
0.45
0.60
• p < 0.05.
14 had vascular dementia and seven had S D L T .
Twenty-one were men and 55 were women.
Overall, the mean CAMCOG scores of the sample
were 43.86 with a standard deviation of 19.30. The
range was 1-86. Patients with Alzheimer's disease had a
mean score of 42.68 (SD 17.94), patients with vascular
dementia had a mean score of 44.50 (SD 24.30) and
patients with S D L T had a mean score of 47.67 (SD
18.0). None of these differences was significant (MannWhitney U test: Alzheimer's disease vs. vascular
dementia: U = 862.5; z = -0.12; p = 0.90, Alzheimer's
disease vs. SDLT: U = 441; z = -0.92; p = 0.36,
vascular dementia vs. S D L T : U = 105.5; z = —0.56;
p = 0.57). Stepwise logistic regression analyses showed
that patients with vascular dementia had significantly
better recent memory (Wald = 5.30; p = 0.02) and
significantly better visual memory (Wald = 7.94;
p = 0.005) than patients with Alzheimer's disease.
Patients with S D L T had significantly better recent
memory (Wald = 5.41; p = 0.02) than patients with
Alzheimer's disease and significantly better visual
memory (Wald = 4.1; p = 0.004) than patients with
vascular dementia. These results are shown in more
detail in Table I.
Table III. Correlation coefficients (Pearson) between
CAMCOG sub-scores and total CAMCOG scores
Orientation
Comprehension
Expression
Praxis
Recent memory
Visual memory
Remote memory
Attention and calculation
Perception
Abstract thinking
Verbal
fluency
Alzheimer's
disease
Vascular
dementia
SDLT*
0.69
0.74
0.77
0.68
0.58
0.55
0.69
0.49
0.61
0.55
0.56
0.84
0.87
0.82
0.75
0.73
0.74
2.92
0.82
0.77
0.62
0.73
0.57
0.87
0.76
0.87
0.36
0.67
0.60
0.68
0.79
0.09
0.54
• Senile dementia of Lewy body type.
The linear regression analysis looking at the variables
sex, age, age at onset, Cornell Depression score,
deafness, number of years of education and psychotic
symptoms showed only an association between male sex
and better total scores on the CAMCOG schedule
(t = 2.47; p = 0.01). Men had a mean CAMCOG score
of 50.85 compared with a mean of 41.34 by women. The
results of the linear regression are shown in more detail
in Table II.
Examining the correlations between the sub-scores
and the overall CAMCOG scores, in patients with
Alzheimer's disease, only one of the 11 sub-scores had a
correlation of <0.50 with the total score. Ten of the 11
sub-scales had a correlation of >0.70 with the total
CAMCOG score amongst patients with vascular
dementia. For patients with S D L T , there were poor
correlations between the overall CAMCOG score and
abstract thinking (R = 0.09) and recent memory
(R = 0.36) respectively. The correlations are shown in
more detail in Table III.
At 1-year follow-up, patients with Alzheimer's
disease showed a mean deterioration of 13.21 (SD
12.61) points on the total CAMCOG schedule,
compared with a deterioration of 13.29 (SD 13.48)
points for patients with vascular dementia and 27.00
(SD 19.77) points for patients with S D L T . There was a
trend for patients with S D L T to have a greater
deterioration in their overall cognitive function than
for patients with Alzheimer's disease (Mann—Whitney
U test: U = 102; z = 1.93; p = 0.05) and patients with
vascular dementia (Mann-Whitney U test: U = 363.5;
z = 1.79; p = 0.07). There was no significant difference
in the overall deterioration of cognitive function
between patients with Alzheimer's disease and vascular
dementia (Mann-Whitney U test: U = 363.5; z = 0.11;
p = 0.90). None of the variables assessed in the linear
regression analysis was significantly associated with a
greater rate of cognitive deterioration; this is shown in
Table IV.
There were no significant differences between the
deterioration of any of the sub-scores in patients with
Alzheimer's disease and vascular dementia. Patients
with S D L T , however, showed a significantly greater
deterioration in verbal fluency (Wald = 5.63; p = 0.02)
212
C. BALLARD ET AL.
Table V. Comparison of depression on CAMCOG sub-scores between patients with different dementias using a logistic
regression analysis, Wald scores and probability (p)
Alzheimer's disease vs.
vascular dementia
Alzheimer 's disease vs.
SDLT
Vascular dementia vs.
SDLT
CAMCOG deterioration
Wald
P
Wald
P
Wald
P
Total
Orientation
Comprehension
Expression
Praxis
Recent memory
Visual memory
Remote memory
Attention and calculation
Perception (Agnosia)
Abstract thinking
Verbal fluency
0.02
0.13
0.13
0.26
0.12
0.67
1.66
0.33
0.25
0.19
0.00
2.38
0.98
0.72
0.71
0.61
0.73
0.41
0.20
0.57
0.62
0.66
0.98
0.12
0.46
3.36
0.45
0.49
0.47
0.10
0.22
0.77
0.10
1.50
1.11
5.63
0.50
0.05
0.50
0.48
0.49
0.76
0.64
0.38
0.75
0.22
0.29
0.02*
3.30
3.56
0.99
1.00
3.37
1.97
6.18
1.07
0.71
0.32
10.94
0.07
0.06
0.32
0.31
0.07
0.16
0.01*
0.30
0.40
0.57
0.0009*
•p < 0.05.
SDLT = senile dementia of Lewy body type.
than did patients with Alzheimer's disease and patients
with vascular dementia (Wald = 10.95; p = 0.0009) and
a significantly greater deterioration in remote memory
than patients with vascular dementia (Wald = 6.18;
p = 0.01). These results are shown in more detail in
Table V.
Discussion
The sample was not representative of dementia patients
in the community although in view of the high
participation rate it should be representative of patients
with mild to moderate dementia in contact with clinical
services. A standardized cognitive assessment was
undertaken at baseline and at 1-year follow-up.
Approximately 70% of the patients were re-interviewed
at that time. A similar proportion of patients with each
type of dementia dropped out of the study. Only three
patients with S D L T did not complete the study, and
they had a lower mean CAMCOG score than those
remaining in the study. This should not have been a
major bias for betvveen-group comparisons as the
comparisons between baseline and 1-year CAMCOG
scores were only made for the 76 subjects completing
the study. The study included patients with Alzheimer's disease, vascular dementia and S D L T , a comparison not previously made.
The overall level of cognitive deterioration was
approximately 13 points on the CAMCOG schedule
in 1 year amongst patients with Alzheimer's disease.
This was similar to the 12 points described by Burns
et al. [2] on the same schedule. The baseline cognitive
scores were similar in patients with the three different
dementia types, although the linear regression analysis
showed male sex to be significantly associated with
higher CAMCOG scores. This is similar to the study
by Henderson and Buckwalter [6] and is of particular
interest in view of recent suggestions that oestrogens
may modulate the progression of cognitive impairment
[24]. Sex was not however an important factor in
explaining the magnitude of cognitive deterioration
over the 1-year follow-up. It is possible that if gender
does exert an influence it may do so at an earlier stage of
the disorder, and a plateau may then be reached.
At the time of the baseline interview, patients with
vascular dementia had significantly less impairment of
recent memory and visual memory than patients with
Alzheimer's disease, although there was no significant
difference in the overall level of cognitive impairment
or verbal fluency. This supports the conclusions of
Almkvist [9] regarding the overall severity of cognitive
impairment, but differences in individual cognitive
domains require further clarification.
Although patients with Alzheimer's disease and
S D L T had a similar level of cognitive impairment at
the time of the baseline interview, patients with S D L T
showed significantly less impairment of recent memory.
This is consistent with neuropathological data suggesting hippocampal sparing [11]. In addition, over the year
of follow-up, patients with S D L T showed a trend
towards a greater overall decline in cognitive function,
with a deterioration of 27 points on the CAMCOG
score. The small number of S D L T patients followed
up for 1 year must be considered when interpreting the
data. Patients with S D L T had significantly greater
deterioration in their verbal fluency than patients with
Alzheimer's disease or vascular dementia. This is
consistent with work [10] suggesting that frontal lobe
functioning is predominantly affected in S D L T
patients.
COGNITIVE DECLINE IN THREE TYPES OF DEMENTIA
Compared with patients with Alzheimer's disease
there was a poor correlation between abstract thinking
and the total CAMCOG score in S D L T patients. This
might form the basis of a diagnostic instrument if a
reference range could be established.
14.
Acknowledgement
We thank the MRC for support.
15.
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Authors' addresses
C. Ballard
MCR Neurochemical Pathology Unit, Newcastle General
Hospital,
Westgate Road, Newcastle upon Tyne NE4 6BE
A. Patel, F. Oyebode
Queen Elizabeth Psychiatric Hospital, Birmingham B15 2QZ
G. Wilcock
Department of Health Care of the Elderly,
Frenchay Hospital, Bristol BS16 1LE
Received in revised form 2 October 1995