Patterns of Neuropsychological Performance in Alzheimer's Disease and Vascular Dementia

PATTERNS OF NEUROPSYCHOLOGICAL PERFORMANCE IN ALZHEIMER'S DISEASE AND V ASCULAR DEMENTIA Ove Almkvist', Lars Backman2, Hans Basun' and Lars-Olof Wahlund3 ('Department of Geriatric Medicine, Karolinska Institute, Huddinge Hospital, Huddinge; 2Section of Psychology, Stockholm Gerontology Research Center, Stockholm; 3Department of Psychiatry, Karolinska Institute, St. Goran's Hospital, Stochkolm)

Alzheimer's disease (AD) and vascular dementia (VD) are the two most common dementia diseases. The degenerative etiology of AD presents as a slowly progressive impairment of higher cortical functions, such as orientation in the environment, construction, word finding, and memory, especially learning of new information. Later on in the pathogenetic process, aphasia, apraxia, and agnosia are typically added to the profile of symptoms (Cummings and Benson, 1983). However, AD may not affect all individuals in a similar manner; subgroups have been suggested in terms of degenerative focus (Martin, Brouwers, Lalonde et aI., 1986), dominant symptoms (Blennow, Wallin and Gottfries, 1991), and rate of progression (Mayeux, Stem and Spanton, 1985). The vascular etiology associated with major cerebral arteries causing large brain infarction may present as a sudden change with selective gross neurobehavioral dysfunctioning, which may disappear or decrease in degree over time. The vascular etiology associated with small-vessel pathology and incomplete infarctions, mainly in subcortical areas, typically present with an insidious onset, affecting a variety of basic cognitive functions, such as mental tempo, attention, memory, and mood. Thus, a wide range of symptoms is included in the vascular etiology making it symptomatically heterogeneous (Erkinjuntti and Sulkava, 1991; Mahler and Cummings, 1991; Wallin and Blennow, 1991). Hypothetically, the different etiologies of AD and VD may be related to different patterns of cognitive and sensory-motor dysfunction. In AD, the primary sensory and motor projection areas are relatively spared from neuropathological changes (Brun and Gustafsson, 1976; Tomlinson, Blessed and Roth, 1970). In VD, however, lesions in primary sensory and motor projection areas can occur following different types of cerebrovascular incidents (CVI). First, hemispheric differences may develop that could be observed by measuring differences between right and left hand in sensory and motor tasks. Second, sensory-motor heterogeneity may result from a selective CVI affecting one sensory modality, although other modalities as well as motor functions may remain unchanged. Third, a noninfarct pathogenetic pathway to VD related to cerebrovascular insufficiency (Wallin and Blennow, 1991) may reduce the metabolic activity all over the brain and result in general cognitive and sensory-motor dysfunction. In contrast, AD patients may show relatively larger differences beCortex, (1993) 29, 661-673

662

O. Almkvist and Others

tween cogmtIve and sensory-motor performance. Fourth, white-matter abnormality affecting subcortical regions of the brain has been found to a larger extent in VD than in AD (Kertesz, Polk and Carr, 1990). The degree of whitematter abnormality is most related to performance in certain neuropsychological tests measuring cognitive and motor speed (Almkvist, Wahlund, AnderssonLundman et aI., 1992). However, previous research has not found any consistent differential neuropsychological patterns of dysfunction in AD and VD (Brinkman, Largen, Cushman et aI., 1986; Erkinjuntti, Laaksonen, Sulkava et aI., 1986; Gandolfo, Vecchia, Moretti et aI., 1986; Mazzucchi, Capitani, Poletti et aI., 1987). Perez, Rivera, Meyer et ai. (1975) found that all subtest scores of the Wechsler Adult Intelligence Scale (WAIS) were higher in VD compared to AD patients, although the VD patients were older than the AD patients. A discriminant analysis, using all the W AIS subtests as well as age and education, could correctly classify 74% of the patients with Block Design and Similarities as the two single best discriminants. However, in the study by Mazzucchi et ai. (1987), the VD patients were also somewhat older than the AD patients, but there were no reliable group differences in W AIS subtests .. Some promising findings concerning specific verbal and visuospatial patterns of impairment, separating AD from VD, have been reported. It has been suggested that intrusion errors (inappropriate recurrence of a response from a previous test) are more common among AD patients (Fuld, Katzman, Davies et aI., 1982), but the evidence on this point is not conclusive (Brinkman et aI., 1986; Fuld, 1986). Hier and associates (1985) observed that VD patients had a more simplified syntax than AD patients, whereas Bayles and Tomoeda (1983) as well as Powell and coworkers (1988) reported less severe naming impairment in VD compared to AD patients. Recently, evidence was presented that AD patients had more pronounced difficulties in understanding and constructing complex grammatical structures, whereas VD patients had particular problems in recognition of words, naming, and repetition (Kontiola, Laaksonen, Sulkava et aI., 1990). Impaired visuospatial functions, such as copying, is said to be a hallmark of AD, and has been shown to be related to severity of cognitive decline in AD, but not in VD (Reichman, Cummings, Flynn et aI., 1990). In a recent study, Gainotti, Parlato, Monteleone et ai. (1992) reported that the frequency of both "closing-in" while copying simple designs and "globalistic" answers in Ravens's Colored Progressive Matrices were significantly higher in AD compared to YD. Concerning memory functions, Erkinjuntti et ai. (1986) could not find any differences between AD and VD patients in memory tests when the groups were stratified according to severity of cognitive decline. Another recent report (Mendez and Mendez, 1991) indicated that AD patients performed better than VD patients in unstructured cognitive tasks (e.g., free description of Cookie Theft Picture and free Tinker Toy constructions). Also, Tierney, Snow, Reid et ai. (1987) suggested that tests measuring noncognitive and behavioral factors should be used to differentiate between these dementia groups, because of a larger number of neuropsychiatric symptoms in VD compared to AD patients (see also Mahler and Cummings, 1991).

Differantiation of AD and VD

663

To summarize, past research has yielded conflicting evidence regarding possible differences in patterns of neuropsychological impairment between AD and YD. The issue of neuropsychological differentiation between these groups remains open, especially concerning sensory-motor functions. As well, most previous studies have not taken into account the possible interaction between type and severity of dementia. The purpose of this study was to compare AD and VD patients with regard to both cognitive and sensory-motor functions across severity of cognitive decline, and to find possible differential neuropsychological patterns in AD and YD.

MATERIALS AND METHOD

Examinations All patients were examined according to a comprehensive procedure, including a somatic examination, neurological status, psychiatric status, blood tests (blood hemoglobin, sedimentation rate, complete blood cell count), serum tests tglucose, sodium, potassium, calcium, chloride, phosphate, iron, creatinine, albumin, ASAT, ALAT, cholesterol, triglyceride, thyroid hormones, vitamin B 12 , folic acid, HIV, Borrelia, syphilis), urinalysis (glucose, protein, pH, microscopic examination), ECG, EEG, chest-radiography, Magnetic Resonance Imaging (MRI; Wahlund, Agartz, Almkvist et ai., 1990), and neuropsychological assessment. Subjects and Diagnosis All patients diagnosed as having AD and VD at the Geropsychiatric Unit, St. Goran's Hospital, between October 1, 1987 and September 1, 1990, were included in the study. One hundred and sixty-seven patients out of 217 referrals met the criteria for clinical diagnosis of dementia according to DSM-III-R (American Psychiatric Association, 1987). Eighty-three demented patients satisfied the criteria for clinical diagnosis of AD according to NINCDS-ADRDA (McKhann, Drachmann, Folstein et ai., 1984). These criteria are probably the most sophisticated available for clinical diagnosis of AD. Between 85% (Tierney, Fisher, Lewis et ai., 1988) and 100% (Martin, Wilson, Penn et ai., 1987) of the cases satisfying these criteria are later found to have the neuropathological changes characteristic of AD. Forty-two demented patients met the following criteria of clinical VD: dementia according to DSM-III-R (American Psychiatric Association, 1987), a history of acute signs and/or symptoms referable to disturbed cerebral circulation in temporal connection with the evolution of dementia, and signs of focal disturbances presented at the neurological examination (Erkinjuntti and Sulkava, 1991). No VD patient had a large brain infarction according to MRI. Nine out of 42 VD patients were diagnosed as having multi-infarct dementia (MID) based on a history of cerebrovascular disease and symptoms indicating a stepwise course. Sixteen patients had dementia of various specific origins (frontal lobe dementia, Parkinson's disease, alcohol abuse, brain tumor) and twenty-six patients had dementia of unknown origin. These forty-two dementia patients were excluded from the study. Fourteen subjects got a psychiatric diagnosis (e.g., depression, schizophrenia) and 36 subjects were not demented, or did not get a psychiatric or any other diagnosis. These 50 nondemented subjects were also excluded from the study. Based on their scores on the MMSE, the AD and VD patients were classified into four levels of severity: very mild (MMSE: 24-30), mild (MMSE: 19-23), moderate (MMSE: 1318), and severe (MMSE: 0-12).

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O. Almkvist and Others

Neuropsychological Assessment

The tests were selected to assess a broad spectrum of basic cognitive functions, verbal ability, visuospatial functions, primary and secondary memory, attention, and sensory-motor functions. All patients were tested by the same experienced neuropsychologist with the MiniMental State Examination (MMSE; Folstein, Folstein and McHugh, 1975); six test from the Wechsler Adult Intelligence Scale - Revised (WAIS-R; Wechsler, 1981): Information, Digit Span, Similarities, Block Design, Object Assembly, and Digit Symbol; two tests of secondary memory from the Wechsler Memory Scale (Wechsler, 1945): Associative Learning and Visual Reproduction; two tests of primary memory: Corsi Block Span (Milner, 1971) and Digit Span Forward, both administered according to an up-and-down technique; the Simple Reaction Time test (Gamberale, Iregren and Kjellberg, 1989); and three Finger-Tapping tests: right hand, left hand, and alternating hands (Gamberale et aI., 1989). After April 1, 1989, the following tests were added to the battery: the Boston Naming test (Kaplan, Goodglass and Weintraub, 1978; items 1-30); and one test of tactile perception: the Tactile Identification of Objects test, with right and left hand separately (Luria, 1966). The WAIS-R fullscale intelligence quotient (FSIQ) was estimated from the six WAIS-R tests.

RESULTS

Demographic characteristics of the subjects are presented in Table I. According to a two-way analysis of variance (ANOV A) on age, with type of dementia (AD, VD) and severity of cognitive decline (very mild, mild, moderate, severe) as between-subjects factors, there were main effects of type of dementia (F = 20.22; d.f. = 1, 116; p< .000 1), and of severity (F = 4.06; d.f. = 3, 116; p<.01), but no interaction effect. The effect of type of dementia was due to the inclusion of patients with an early onset, which occurred exclusively in AD in our sample. This is a standard finding indicating that AD generally has an earlier onset than VD (Cummings and Benson, 1983). The effect of severity resulted from a gradual increase in severity with increasing age in both groups. A X2 test on sex distribution showed no effects whatsoever (ps> .10). Regarding years of education, a two-way ANOV A yielded a significant interaction between type and severity of dementia (F = 3.40; dJ. = 3, 75; p<.05), but no main effects. The interaction effect was due to a relatively long education in the very mildly demented AD patients, and in the severely demented VD patients. Neuropsychological Tests

In Table II, the means and standard deviations of the raw scores on the neuropsychological tests for the AD and VD patients are presented across severity of dementia. A 2 (type) X 4 (severity) ANOVA was conducted for each neuropsychological measure. A summary of these analyses is displayed in Table III. Type of dementia was statistically significant in six tests: Similarities (F=5.21; d.f.= 1, 101; p<.05), Object Assembly (F= 12.27; d.f.= 1, 101; p<.OOl), Digit Symbol (F = 11.25; d.f. = 1, 82; p<.OOl), Simple Reaction Time (F=4.14; dJ. = 1, 105;p<.05), Finger-Tapping: Left Hand (F=4.67; d.f. = 1, 104; p<.05), and Finger-Tapping: Alternating Hands (F= 12.23; d.f.= 1, 91; p<.OOl). All these differences were in favor of the AD patients. However, the proportion of variance accounted for by type of dementia was low for all these

22 3/19 74.8±7.3 51-86 9.3± 3.3

14 717 69.9±7.2 61-84 11.3±4.2 23 9/14 76.6±6.1 62-87 9.2±3.3

24 2/22 74.6±6.4 61-83 8.0±1.8

TABLE ((

Severe

Moderate 10 317 77.3±3.3 73-82 8.2±3.1

Very mild 12 517 79.4±4.8 70-88 83 . ±2.7

Mild

VD

Severe 63.4±6.4 4.5±2,7 5.6±3.3 2.5±3.2 O.9±2.1 5.8±6,6 3.9±4.4 19.3±5.0 3A± 1.6 O.9±1.4 4.2±O.7 3.1±O.8 439±146 49±8 43±9 54±12 3.2±1.8 4.0±2.7

Moderate 72A±7 ,7 96 . ±5.6 8.4±2.4 6.0±4.9 2,8±4.8 9.0±5.8 6.7±6,3 23.4±3.7 5.3± 1.6 O.9±1.l 5.0±O.8 3.5±O.7 364±122 50±1O 46±11 57±15 2.8±1.0 3.9±2.6

Mild 82,8 ± 7A 13.1±4,6 1O.5±2.4 12.3±5.9 7.1±5A 13.7±6.4 17.8±8.0 24.1±4.5 7.1 ±2.4 2.6±1.4 5.6±0.6 4 .2± O.6 355±133 53±9 48±1l 60±15 3.8±2.1 2.5±1.2

Very mild

87.4±7,O 15,2±5.3 1O.2±2A 14.5±4.4 12.9±7.4 17.1±8.3 22.5±8.7 27,5±2.2 9.1 ±3.3 4.1±2.6 5.3±O.6 4.3±0.6 270±78 55±13 50±12 64±18 1.9±O.6 1.8±OA

WAIS-R: FSIQ WAIS-R: Information WAIS-R: Digit Span WAIS-R: Similarities WAIS-R: Block Design WAIS-R: Object Assembly WAIS-R: Digit Symbol Boston Naming WMS : Associative Learning WMS : Visual Reproduction Digit Span Forward Corsi Block Tapping Span Simple Reaction Time (msec) Finger-Tapping: Right Hand Finger-Tapping: Left Hand Finger-Tapping: Alternating Hands Tact. Ident. Objects: Rt Hd (sec) Tact. Ident. Objects: Lt Hd (sec)

AD

"

80.9±3.3 13.1 ±3.1 9.9±2,2 11.3±4.0 7,9±6.0 8,8±4.6 11.1 ±5.3 26.1 ±2.3 7.4±2.8 2.9±2.8 5A±O.7 4.0±O.7 326±60 52±11 44±10 46±1l 2.1 ± 1.4 3.7±1.8

Very mild

78,9±4.7 1O,7±3,5 7 9. ±3,1 9.6±4.8 7.4±6.3 9.9±5.8 12A±5A 24.6±2.9 68 . ±2.2 25 . ± 1.4 5.2±O.6 4.0±O.5 371±143 50±11 45±1O 49±14 3.1±1.7 3.3±3.1

Mild

VD

Neuropsychological Performance (mean±S.D.) in AD and VD Patients Across Severity of Dementia

Mild

Very mild

AD

Neuropsychological test

N Sex (males/females) Age (mean±S.D.) Age range Education (mean±S.D.)

TABLE I

Subject Characteristics

72.3±5.8 9.2±4.0 9.0±2.4 5.1 ±4.1 1.2± 1.3 5.9±4.9 5.6±3.4 24 .6±3.3 5.4±2.1 O.9±O.7 5.1±O.8 3.7±O.4 415±102 49±13 39±12 43±15 3.5±2.1 4.2±2.2

Moderate

12 3/9 79.1 ±5.4 70-88 8.3 ± 1.7

Moderate

63,8± 1.7 53 . ±4.7 5,O±2A 0.3 ±O.8 O,7±O.8 3.1±2.8 4,O±6.9 21.8± 1.3 4.3±0.9 O.9±O.6 4.6 ±0.8 3.3 ±O.8 524±114 46±16 41±1 2 57±12 2.0± 1.6 33 . ±2.7

Severe

8 2/6 81.8±4.3 75-88 12.0±5.8

Severe

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measures (£if=.02-.10); the overlap between the two patient groups was substantial, which is illustrated by the Digit Symbol data in Table IV. As well, it may be noted that the comparisons between measures are not independent of each other and thus values of p<.05 must be accepted with caution. For all tests assessing general intelligence, language ability, visuospatial functions, memory, and attention, there was a significant effect of severity of dementia (see Tables II and III). However, severity of dementia did not affect performance in any of the sensory-motor tasks (ps>.lO). In addition, for none of the tests the interaction between type and severity of dementia approached significance (ps> .10). TABLE III

Summary Table of Statistical Analyses

Neuropsychological test W AIS-R: FSIQ WAIS-R: Information WAIS-R: Digit Span WAIS-R: Similarities WAIS-R: Block Design WAIS-R: Object Assembly WAIS-R: Digit Symbol Boston Naming WMS : Associative Learning WMS: Visual Reproduction Digit Span Forward Corsi Block Tapping Span Simple Reaction Time Finger-Tapping: Right Hand Finger-Tapping: Left Hand Finger-Tapping: Alternating Hands Tactile Ident. Objects: Right Hand Tactile Ident. Objects: Left Hand

Type

Severity

TXS

n.s. n.s. n.s.

*** * ** *** ***

n.s. n.s. n.s. n.s. n.s. n.s. n.s. n. s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s.

*

n.s.

*** * ** n.s. n.s. n.s. n.s. n.s.

*

n.s.

*

*** n.s. n.s.

***

*** *** *** *** *** *** *** ** * n.s. n.s. n.s. n.s. n.s.

n.s. =p >. lO; *=p < .O.5; ** = p < .OI ; ***= p <.OOI.

Derived Measures

Based on etiological models of AD and VD, three hypotheses concerning possible differentiating indices based on sensory-motor performance were formulated. The first hypothesis relates to a possible differences between right and left hand in Finger-Tapping and Tactile Identification of Objects. The analyses were performed on z-transformed raw scores using a group of healthy aged individual as reference group (N = 28, 16 females and 12 males; mean::':: S.D. for age: 78.4::'::S.D.; mean::':: S.D. for years of education: 9.9::'::3.9) (Wahlund et al., 1990). An ANOVA on quadrated z-transformed difference scores for Finger-Tapping yielded a significant difference between AD and VD patients (F = 8.93; d.f. = 1, 104; p<.Ol), which showed a larger difference between the right and the left hand in VD compared to AD patients. Severity and the interaction effect were nonsignificant (ps > .l 0). A corresponding analysis for Tactile Identification of Objects did not yield any statistically sig-

Differantiation of AD and VD

667

nificant results (ps> .10). The second hypothesis, assuming that sensory-motor heterogeneity might differentiate between AD and VD, was confirmed by an ANOV A performed on the standard deviations of three Finger-Tapping tests (F = 9.65; d.f. = 1, 104; p<.Ol), again showing a larger heterogeneity in VD than in AD patients, as illustrated in Figure 1. Neither severity nor the interaction effect were significant in these analyses (ps> .10). A similar analysis of the standard deviations in Tactile Identification of Objects yielded no significant effects (ps> .10). Finally, we tested the hypothesis that sensory-motor performance is relatively more impaired in VD compared to AD patients. This hypothesis was tested by ANOV As on two difference indices beween global cognitive functions and specific sensory or motor functions expressed as z-values (FSIQ - mean of three Finger-Tapping tests; FSIQ - mean of two tests of Tactile Identification of Objects). There were no main or interaction effects in any of these analyses (ps>.1O).

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mild

moderate

severe

Severity of Dementia Fig. 1 - Heterogeneity in Finger-Tapping (S.D.) in AD and VD Patients Across Severity of Dementia.

Differentiating Formulas

In order to evaluate the discriminative power of the present neuropsychological tests, a stepwise discriminant analysis was performed on the six tests resulting in significant group differences (Similarities, Object Assembly, Digit

O. Almkvist and Others

668

TABLE IV

Frequency Distribution of WAIS-R: Digit Symbol Scores for AD and VD Patients Across Severity of Dementia

Severity of dementia Very mild Digit symbol score

AD

0-10 11-20 21-30 31-40 51Missing Total

6 5 1 1 1 14

Mild

Moderate

Severe

VD

AD

VD

AD

VD

AD

VD

4 3 1

4 6 9

3 5 1

15 2 1

7

12 1

2 1

1 9

3 22

3 12

6 24

5 12

10 23

5 8

TABLE V

Predicted Diagnosis and Clinical Diagnosis in AD and VD Patients

Clinical diagnosis Predicted diagnosis

AD

VD

Total

AD VD Total*

44 16 60

10 23 33

54 39 93

* Excluding

the severely demented patients.

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Canonical Variate Fig. 2 - Frequency Distribution of AD and VD Patients on the Canonical Variate.

3.0

Dijferantiation of AD and VD

669

Symbol, Simple Reaction Time, Finger-Tapping: Left Hand, Finger-Tapping: Alternating Hands) and two significant indices of variability in motor function (difference between right hand and left hand in Finger-Tapping and standard deviation of the three Finger-Tapping tests). When all four levels of dementia severity were included in the analysis, four significant (X 2 = 16.6; d.f. = 4; N = 83; p<.003) variables appeared (standardized discriminant coefficients within parentheses): Object Assembly (.41), Simple Reaction Time (.44), Finger-Tapping: Alternating Hands (.76), and squared difference between hands in Finger-Tapping (- .61), with a canonical correlation coefficient of .44. The classification hit rate was 67% including all patients (56/ 83 AD patients and 28/42 VD patients). The distribution of patients on the canonical variate is shown in Figure 2. The calculation was repeated for each level of dementia severity in order to examine whether the set of differentiating variables varies across the disease process. For the very mildly demented patients, a significant discriminant function (X 2 = 10.9; d.f. = 3; N = 19; p<.02) was obtained with a considerable canonical correlation coefficient (r = .71) and three significant variables: Object Assembly (.57), Digit Symbol (.45), and FingerTapping: Left Hand (.47), with 78% of the cases correctly classified (9/14 AD patients and 9/9 VD patients). '~ In the group of mildly demented patients, 71% were correctly classified (16/ 22 AD patients and 8/12 VD patients) by means of a significant function (X 2 ; dJ. = 2; N = 24; p<.04) using two variables: Digit Symbol (.74), and the squared difference between right and left hand in Finger-Tapping (- 0.86). The canonical correlation coefficient was .53. 69 percent (19/24 AD patients and 6/12 VD patients) of the moderately demented patients were correctly classified with a significant discriminant function (X 2 = 9.7; d.f. = 3; N = 24; p<.03) and a canonical correlation coefficient of .61, using three variables: Similarities (.57), Finger-Tapping: Alternating Hands (.63), and the standard deviation of the Finger-Tapping tests (- 1.03). For the severely demented patients, the discrimination function was nonsignificant (p> .10). A summary of predicted versus clinical diagnosis is presented in Table V. The overall hit rate was 72% when classification was performed separately for each level of dementia severity, excluding the severely demented patients. The discriminant analyses presented so far were based on a hypothesisgeneration approach, and no statistical criteria for inclusion of variables were used. In order to evaluate further the discriminative power of the tests, the overall analysis was repeated using a strict criterion for inclusion of variables (p<.05). Two finger-motor variables: Finger-Tapping: Alternating Hands (.74), and the squared difference between hands in Finger-Tapping (- .69) appeared in the discriminant function (X 2 = 13.04; d.f. = 2; N = 83; p<.OO2), yielding an overall hit rate of 65% (59/83 AD patients and 22/42 VD patients). DISCUSSION

The two groups of dementia patients differed in age although they were matched for severity of dementia. This result is due to the fact that AD typically has an earlier onset than VD (Cummings and Benson, 1983). Consequently, if

670

O. Almkvist and Others

the two groups had been matched on age, a difference would have been expected in general level of cognitive functioning in favor of the VD patients (cf. Erkinjuntti et aI., 1986; Gainotti et aI., 1992; Perez et aI., 1975). A striking finding in this study was the strong effect of severity of dementia on all cognitive measures, and the general lack of such an effect on sensorymotor performance in both AD and VD patients. This pattern of results indicates that severity of dementia as measured by the MMSE may be thought of as a cognitive rather than a sensory-motor phenomenon. Note that a lack of relationship between severity of dementia and sensory-motor functioning was seen also in the VD patients. This result is in disagreement with etiological models of VD associating focal disturbances with dementia (Erkinjuntti and Sulkava, 1991; Mahler and Cummings, 1991). An important finding was the absence of an interaction between type and severity of dementia in all neuropsychological measures. These results suggest that the pattern of cognitive impairment across the course of dementia is similar in AD and YD. This functional similarity is interesting to note in light of assumed differences between these dementia types in pathological mechanisms (Tomlinson et aI., 1970; Wallin and Blennow, 1991). Another major finding was the statistiCally significant group differences between AD and VD patients in a number of neuropsychological tests and derived measures, pointing at a weak, but possible dissociation of dysfunction patterns. The AD patients were less impaired in tests of visuospatial functioning (Object Assembly), and motor functions (Finger-Tapping and derived measures of intraindividual variability in Finger-Tapping), but the overlap between AD and VD patients was considerable in these tests. Those test in which the VD patients performed worse than the AD patients all draw on motor or cognitive speed. In many of these tests, performance has been found to be related to white matter abnormalities that are more common in VD than in AD patients (Almkvist et aI., 1992). Thus, the obtained differences between AD and VD patients may be due to a more pronounced subcortical involvement in VD compared to AD (Cummings, 1986). There were no reliable differences between AD and VD patients in general intelligence as measured by the FSIQ from WAIS-R, secondary memory as measured by Associative Learning and Visual Reproduction from WMS, or primary memory as measured by Digit Span Forward and Corsi Block Span. These results indicate that the two patient groups were similar in intelligence and memory, although the VD patients were somewhat older that the AD patients. In addition, a discriminant analysis on single tests and derived measures was moderately successful in differentiating between AD and VD patients, using results from cognitive and finger-motor tasks that are speed-related. Using a strict criterion for inclusion of variables into the discriminant analysis, it was evident that the discrimination was predominantly based on tests drawing on motor speed. The discriminative power of the tests used was highest for very mild and mild dementia. No significant discriminant function was obtained for the severely demented patients. This pattern of data is reasonable given that the progression of both AD and VD is likely to result in gradually more global disturbances. Slightly more than 70% of the patients were correctly classified

Differantiation of AD and VD

671

when the classification was done separately for each level of severity, excluding the severely demented patients. There are several reasons for the imperfect classification. One reason may be that the diagnostic procedure employed did not allow for mixed cases, although such cases exist and may be recognized at autopsy. The prevalence of mixed cases has been estimated from neuropathological data to about 10% (Gustafson, 1990). A second reason for the imperfect differentiation of AD and VD may be that, for may cognitive functions, AD and VD are functionally rather similar, and a perfect discrimination should thus not be expected. This interpretation implies a similarity in regional brain affection in AD and VD despite different pathogenetic mechanisms. The present finding that AD and VD are functionally similar with regard to patterns of neuropsychological impairment across severity of dementia, supports the idea that the evolution of VD typically is based on a general rather than a selective affection of the brain. This interpretation runs counter to the influential concept of multi-infact dementia (MID) introduced by Hachinski (1974), but it is in agreement with a multifactorial view of VD, including mechanisms of general malfunction of cerebrovascular circulation (e.g., Loeb, 1990; Scheinberg, 1988; Wallin and Blennow, 1991). , The general conclusion from this study, that it is not possible with a high rate of success to differentiate whole groups of AD and VD patients by using neuropsychological test results, is in agreement with previous studies (Brinkman et aI., 1986; Erkinjuntti et aI., 1986; Gandolfo et aI., 1986; Mazzucchi et aI., 1987; Perez et aI., 1975; Tierney et aI., 1987). Thus, the main conclusion of this research is negative. Nevertheless, this study has shown that some neuropsychological tests measuring cognitive and motor speed may be useful in differentiating between AD and VD patients. These tests are related to white matter abnormalities (Almkvist et aI., 1992) and are sensitive to subcortical lesions, which are more common in VD than in AD. ABSTRACT

The hypothesis that Alzheimer's disease (AD) and vascular dementia (VD) may be associated with specific patterns of neuropsychological dysfunction was tested by assessing sensory-motor performance, attention, memory, visuospatial functions, verbal ability, and intelligence in AD (N = 83) and VD (N = 42) patients stratified into four levels of severity based on the Mini-Mental State Examination. Results showed a progressive deterioration due to severity of dementia in both AD and VD patients in all cognitive tasks, but not in the sensory-motor tasks, and no significant interaction between type and severity of dementia in any measure, indicating a similar pattern and course of neuropsychological deterioration in AD and YD. Yet it was possible to differentiate the two groups with moderate success using tests drawing predominantly on motor speed and, to a lesser extent, on cognitive speed. In all these speeded tests, the AD patients outperformed the VD patients. Acknowledgments. The study was conducted in partial fulfilment of the doctoral degree requirements under the supervision of the second author. Parts of this research were presented at the 4th Cognitive Aging Conference, Atlanta, U.S.A., April 9-12, 1992. The preparation of this article was supported by grants from the Bank of Sweden Tercentenary Foundation to Lars Backman, and from Gun and Bertil Stohne's Foundation, Fredrik and Ingrid Thuring's Foundation, and Petrus and Augusta Hedlund's Foundation to Bengt Winblad.

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