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Cognitive decline in patients with Alzheimer's Disease, vascular dementia and senile dementia of Lewy body type.

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 SDLT 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 CAMDEX 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 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 w as 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 Mann-Whitney 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 I 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 SDLT. 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 follow-up. 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. Twenty-eight of the patients not completing follow-up had Alzheimer's disease, five had vascular dementia and three had SDLT. Their mean baseline CAMCOG score was 38.58 (Alzheimer's disease mean 39.4, vascular dementia mean 39.2, SDLT mean 30.0). Fifty-three of the patients completing the repeat cognitive testing suffered from Alzheimer's disease, 14 had vascular dementia and seven had SDLT. 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 SDLT had a mean score of 47.67 (SD 18.0). None of these differences was significant (Mann-Whitney 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. SDLT: 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 SDLT 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 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       Alzheimer's         Vascular
              disease vs.       disease vs.         dementia vs.
              vascular          senile              senile
              dementia          dementia of         dementia of
                                Lewy body type      Lewy body
                                                    type

CAMCOG score     Wald     p     Wald      p      Wald      p

Total           0.19    0.66     0.22    0.64    1.51    0.22
Orientation     0.46    0.50     2.10    0.15    0.82    0.37
Comprehension   2.01    0.16     0.11    0.74    1.56    0.21
Expression      0.25    0.62     0.79    0.37    1.29    0.26
Praxis          1.27    0.26     0.55    0.46    0.40    0.53
Recent memory   5.30    0.02(*)  5.41    0.02(*) 0.05    0.82
Visual memory   7.94    0.005(*) 0.18    0.67    4.18    0.04
Remote memory   0.73    0.39     1.82    0.18    2.09    0.15
Attention and
  calculation   0.43    0.51     0.10    0.75    0.33   0.57
Perception
  (agnosia)     1.89    0.17     0.45    0.50    0.20   0.66
Abstract
  thinking      1.15    0.28     0.18    0.67    0.01   0.93
Verbal
  fluency       0.22    0.64     0.03    0.85    0.26   0.61

(*) p < 0.05.




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.
Table II. A linear regression analysis of variables associated
with the severity of cognitive impairment: T-values and
probability (p)

Variable                            t     p

Female sex                        2.47   0.01(*)
Age at onset of dementia          0.07   0.94
Age of patient at assessment     -0.63   0.53
Cornell depression score          0.28   0.78
Deafness                          0.43   0.67
Number of years of education     -0.51   0.96
One or more psychotic symptom    -0.75   0.45

(*) p < 0.05.




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 SDLT, 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.
Table III. Correlation coefficients (Pearson) between
CAMCOG sub-scores and total CAMCOG scores

                            Alzheimer's    Vascular
                            disease       dementia    SDLT(*)

Orientation                 0.69           0.84      0.57
Comprehension               0.74           0.87      0.87
Expression                  0.77           0.82      0.76
Praxis                      0.68           0.75      0.87
Recent memory               0.58           0.73      0.36
Visual memory               0.55           0.74      0.67
Remote memory               0.69           2.92      0.60
Attention and calculation   0.49           0.82      0.68
Perception                  0.61           0.77      0.79
Abstract thinking           0.55           0.62      0.09
Verbal fluency              0.56           0.73      0.54

(*) Senile dementia of Lewy body type.




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 SDLT. There was a trend for patients with SDLT 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.
Table IV. Linear regression analysis of variables associated
with the magnitude of cognitive decline over 1 year: t statistic
and p values

Variables                           t      p

Female sex                         0.11    0.89
Age of onset of dementia           0.53    0.59
Age of patient at assessment       0.12    0.91
Cornell depression score           0.24    0.81
Deafness                           0.03    0.93
Number of years of education       0.76    0.45
One or more psychotic symptom     -0.83    0.60




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 SDLT, however, showed a significantly greater deterioration in verbal fluency (Wald = 5.63; p = 0.02) 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.

[TABULAR DATA V OMITTED]

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 SDLT 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 between-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 SDLT, 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 SDLT had a similar level of cognitive impairment at the time of the baseline interview, patients with SDLT 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 SDLT 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 SDLT patients followed up for 1 year must be considered when interpreting the data. Patients with SDLT 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 SDLT patients.

Compared with patients with Alzheimer's disease there was a poor correlation between abstract thinking and the total CAMCOG score in SDLT patients. This might form the basis of a diagnostic instrument if a reference range could be established.

Acknowledgement

We thank the MRC for support.

References

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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 ILK

Received in revised form 2 October 1995
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Author:Ballard, C.; Patel, A.; Oyebode, F.; Wilcock, G.
Publication:Age and Ageing
Date:May 1, 1996
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