Comparison of Different Clinical Criteria (DSM-III, ADDTC, ICD-10, NINDS-AIREN, DSM-IV) for the Diagnosis of Vascular Dementia

Comparison of Different Clinical Criteria (DSM-III, ADDTC, ICD-10, NINDS-AIREN, DSM-IV) for the Diagnosis of Vascular Dementia T. Pohjasvaara, MD, PhD; R. Mäntylä, MD; R. Ylikoski, MA; M. Kaste, MD, PhD; T. Erkinjuntti, MD, PhD Background Purpose The criteria for vascular dementia (VaD) include definition of the cognitive syndrome the vascular cause. Different criteria for dementia identify different frequencies clusters of patients. In addition, variation in defining the cause etiology may have an effect. We compared different clinical criteria for VaD in series of patients with poststroke dementia. Methods The study group comprised 107 patients fulfilling the Diagnostic Statistical Manual of Mental Disorders, Third Edition (DSM-III) definition for dementia from a cohort of consecutive patients with ischemic stroke who completed a comprehensive neuropsychological test battery MRI. The mean age (SD) of the patients was 71.4 (7.6) years. The definitions of vascular cause of VaD were those of the DSM-III (1980), Alzheimer s Disease Diagnostic Treatment Centers (ADDTC; 1992), International Statistical Classification of Diseases, 10th Revision (ICD-10; 1992), National Institute of Neurological Disorders Stroke Association Internationale pour la Recherche et l Enseignement en Neurosciences (NINDS-AIREN; 1993), Diagnostic Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; 1994). Results The number of cases that could be classified as VaD according to the different criteria varied considerably: 36.4% (n 39) by DSM-III, 86.9% (n 93) by ADDTC, 32.7% (n 35) by NINDS-AIREN, 36.4% (n 39) by ICD-10, 91.6% (n 98) by DSM-IV criteria. The concordance between DSM-III/ICD-10 was perfect (100%; 1.0), between ICD-10/NINDS-AIREN ADDTC/DSM-IV good to moderate (85.0% 87.3%; 0.87 0.37, respectively), but otherwise poor between the other criteria. Only 31 patients fulfilled all the criteria for VaD applied. Major discriminating factors between the criteria were requirement of (1) focal neurological signs, (2) unequal distribution of deficits in higher cortical functions, (3) evidence of relevant CVD based on brain imaging findings. Conclusions Current criteria of VaD identify different frequencies clusters of patients are not interchangeable. Optimally, prospective studies with clinicopathological correlation could identify new criteria. Meanwhile, focus on more homogeneous subtypes (eg, small-vessel subcortical VaD) detailed neuroimaging criteria could improve the diagnostics. (Stroke. 2000;31:2952-2957.) Key Words: dementia diagnosis stroke Critical elements in the concept diagnosis of vascular dementia (VaD) incorporate defining the cognitive syndrome the vascular cause. Recently, the effect of different criteria for defining the cognitive syndrome, the dementia syndrome, has been shown. 1,2 Accordingly, different definitions determine different prevalence estimates identify different groups of subjects. Furthermore, differences in defining the vascular cause etiology may add to the variation. 3 6 A limitation has been that all the clinical criteria applied are consensus criteria that are neither derived from prospective community-based studies with clinicopathological correlates of vascular factors affecting the cognition nor based on detailed natural histories. 7 Currently, the most widely used criteria for VaD include the Diagnostic Statistical Manual of Mental Disorders (DSM), Alzheimer s Disease Diagnostic Treatment Centers (ADDTC), International Statistical Classification of Diseases (ICD), National Institute of Neurological Disorders Stroke Association Internationale pour la Recherche et l Enseignement en Neurosciences (NINDS-AIREN) criteria. 5,8 10 In the present study we studied the effect of different clinical definitions of VaD in case finding among patients with poststroke dementia. Received June 20, 2000; final revision received August 22, 2000; accepted August 22, 2000. From the Department of Clinical Neurosciences, Memory Research Unit (T.P., R.Y., T.E.), Stroke Unit (M.K.), Department of Radiology (R.M.), Helsinki University Central Hospital (Finl). Reviews for this manuscript were directed by Mark L. Dyken, MD. Correspondence to Timo Erkinjuntti, MD, PhD, Memory Research Unit, Department of Clinical Neurosciences, Helsinki University Central Hospital, PO Box 300, FIN-00029 HYKS, Finl. E-mail Timo.Erkinjuntti@hus.fi 2000 American Heart Association, Inc. Stroke is available at http://www.strokeaha.org 2952

Pohjasvaara et al Different Clinical Criteria for Vascular Dementia 2953 TABLE 1. Elements of 5 Guidelines for the Diagnosis of Vascular Cause of Dementia Among the 107 Patients Diagnosed as Demented According to DSM-III Criteria DSM-III ADDTC ICD-10 NINDS-AIREN DSM-IV Stepwise deterioration 1 Patchy (unequal) distribution of cognitive deficits Focal neurological signs 2 4 Focal neurological symptoms 4 2 Ischemic strokes 2 3 Evidence of significant CVD 2 3 Etiologic relation to the disturbance Temporal relationship between stroke dementia 2 (1) indicates obligatory;, not needed; 1, either onset of dementia within 3 mo after a recognized stroke /or abrupt deterioration in cognitive functions, or fluctuating, stepwide progression of cognitive deficits; 2, evidence of 2 ischemic strokes by history, or neurological signs, /or neuroimaging studies, or occurrence of a single stroke with a clearly documented temporal relationship to the onset of dementia evidence of 1 infarct outside the cerebellum by CT or T1-weighted MRI; 3, either multiple strokes or a single strategically placed infarct; 4, focal neurological signs symptoms or laboratory evidence indicative of CVD that are judged to be etiologically related to the disturbance. Subjects Methods The Helsinki Stroke Aging Memory Study included 486 consecutive patients aged 55 to 85 years with ischemic stroke. Of these 486 patients, 337 (69.3%) completed MRI of the head a comprehensive neuropsychological examination 3 months after stroke. 2,11,12 The mean age (SD) of the patients was 71.4 (7.6) years. All the subjects underwent a structured medical neurological history a structured clinical neurological examination. 2 Cognitive domains assessed by the neuropsychological test battery included memory functions (short- long-term memory), abstract thinking, judgment, aphasia, apraxia, agnosia, constructional difficulty, including visuospatial constructional functions. 11 The criteria for dementia were those of the Diagnostic Statistical Manual of Mental Disorders, Third Edition (DSM-III), 13 the diagnosis required impairment in short- or long-term memory in one other cognitive domain, as well as a cognitive decline sufficiently severe to impair everyday social functioning, including the patient s ability to work perform activities of daily living. Assessment of both basic complex activities of daily living, reflecting functions before 3 months after the index stroke, was based on 5 structured interview scales with the patient a knowledgeable informant, as well as the neurological examination. 2 Altogether, 107 patients fulfilled the definition of dementia according to the DSM-III criteria constitute the present study group, which has been clinically detailed in a previous report. 11 Definitions of vascular cause of VaD applied included the DSM- III, 13 ADDTC for probable ischemic VaD, 14 International Statistical Classification of Diseases, 10th Revision (ICD-10), 15 NINDS- AIREN for probable VaD, 16 Diagnostic Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). 17 Variables included in the 5 diagnostic guidelines applied are detailed in Tables 1 2. Focal neurological signs in the DSM-III DSM-IV definitions include exaggeration of deep tendon reflexes, extensor plantar response, pseudobulbar palsy, gait abnormalities, weakness of an extremity; in the ICD-10 criteria, unilateral spastic weakness of the limbs, unilaterally increased tendon reflexes, an extensor plantar response, or pseudobulbar palsy; in the NINDS-AIREN criteria, hemiparesis, lower facial weakness, Babinski sign, sensory deficit, hemianopia, dysarthria. In the present study presence of focal neurological signs included at least 1 of the following: hemianopia, lower facial weakness, dysarthria, motor or sensory hemisyndrome, hemiplegic gait, or positive Babinski sign. Patchy distribution of deficits (ie, affecting some functions, but not others) in DSM-III deficits in higher cognitive functions unequally distributed (with some function affected others relatively spared) in ICD-10 were recorded positive in the present study if at least 1 of the cognitive domains assessed was rated as normal. MRI was performed with a 1.0-T device (Siemens Magnetom). 12 The number, size, location of infarcts were recorded. The sites included lobes, vascular territories, specific locations. 12 Infarction was defined as lacunar if situated in the deep white or gray matter areas irrigated by the deep perforants if the diameter was 3to9mm. 18 Large-vessel infarcts were those located in the cortical or cortico-subcortical areas. White matter lesions were rated in periventricular, deep, watershed, subcortical white matter areas, as detailed previously. 12,19 Extensive periventricular white matter lesions included extending caps (hyperintensities classified on the basis of size shape), or irregular halo, or diffusely confluent lesions, or extensive white matter change, or a combination thereof. 20 Reliability of the visual rating was tested by reviewing 60 MR scans independently by the same rater (R.M.), by a board-certified neuroradiologist, by a general radiologist. The weighted values for intraobserver agreement were 0.90 for periventricular caps, 0.93 for linings halos, 0.95 for deep white matter hyperintensities. The corresponding values for interobserver agreement were 0.82 to 0.84 for caps, 0.72 to 0.82 for linings halos, 0.77 to 0.84 for deep white matter hyperintensities. 12 Clinically, all the patients were examined by the same neurologist (T.P.), all the cases were reviewed together with the senior neurologist (T.E.). The study was approved by the ethics committee of the Department of Clinical Neurosciences, Helsinki University Central Hospital, Helsinki, Finl. The study design was first explained fully; written information was offered to the patients a knowledgeable informant, if they agreed to participate, a written consent form was signed by a patient or a knowledgeable informant if the patient was obviously demented or unable in any other way to sign a consent form. In the statistical procedure we compared the effect of the definition of vascular cause on the 107 patients with a diagnosis of DSM-III dementia. The 2 test was applied for categorical data comparing patients diagnosed with VaD by different paradigms. Concordance (overlapping cases) was computed as the quotient of the cases classified as VaD by both of the criteria applied the number of cases classified as VaD by either of the criteria. Agreement between the criteria was also calculated with the use of statistics, indicating how much better the agreement is than that of chance, with a value of zero indicating no agreement better than chance. The statistics were analyzed with the BMDP program. 21 Results The frequency of patients fulfilling definitions for vascular cause varied considerably when algorithms for different

2954 Stroke December 2000 TABLE 2. Diagnosis of Vascular Cause of VaD According to DSM-III, ADDCT, ICD-10, NINDS-AIREN, DSM-IV Criteria in Patients With DSM-III Poststroke Dementia (n 107) in the Helsinki Stroke Aging Memory Study Cohort No. % DSM-III Stepwise deterioration, with patchy distribution of cognitive deficits focal neurological signs symptoms evidence from history, physical examination, or laboratory tests of significant CVD that is judged to 107 105 40 107 100.0 98.1 37.4 100.0 be etiologically related to the disturbance VaD according to DSM-III criteria 39 36.4 ADDCT Evidence of 2 ischemic strokes by history, or neurological signs, /or neuroimaging studies (CT or T1-weighted MRI), or occurrence of a single stroke with a clearly documented temporal relationship to the onset of dementia evidence of 1 infarct outside the cerebellum 28 78 12 103 26.2 72.9 11.2 96.3 by CT or T1-weighted MRI VaD according to ADDTC criteria 93 86.9 ICD-10 Deficits in higher cognitive functions are unequally distributed clinical evidence of focal brain damage (signs) evidence from the history, examination, or tests of a significant CVD, which may reasonably be judged to be etiologically related to the dementia (eg,a history of stroke, evidence of cerebral infarction) 105 40 107 98.1 37.4 100.0 VaD according to ICD-10 criteria 39 36.4 NINDS-AIREN CVD defined by the presence of focal signs on neurological examination evidence of relevant cerebrovascular disease by brain imaging (MRI) including 40 37.4 multiple large-vessel infarcts 27 25.2 or single strategically placed infarct (angular gyrus, 12 11.2 thalamus, basal forebrain, PCA or ACA territories) or multiple basal ganglia white matter lacunes 44 41.1 or extensive periventricular white matter lesions 69 64.5 or combinations thereof 92 86.0 A relationship between the above 2 disorders manifested or inferred by the presence of 1 of the following Onset of dementia within 3 mo after a recognized stroke 107 100.0 Abrupt deterioration in cognitive functions, or fluctuating, stepwise progression of 107 100.0 cognitive deficits VaD according to NINDS-AIREN criteria 35 32.7 DSM-IV Focal neurological signs symptoms or laboratory evidence indicative of CVD that are judged to be etiologically related to the disturbance VaD according to DSM-IV criteria 98 91.6 PCA indicates posterior cerebral artery; ACA, anterior cerebral artery. 40 91 37.4 85.1

Pohjasvaara et al Different Clinical Criteria for Vascular Dementia 2955 Focal neurological signs required to be present in the DSM- III, ICD-10, NINDS-AIREN criteria were recorded in 40 patients (37.4%). In the present series, presence of focal signs was the main discriminating factor between these 3 criteria ADDTC or DSM-IV criteria (Table 4). Further important discriminating factors included requirement of unequal distribution of deficits in higher cognitive functions evidence of relevant CVD based on brain imaging findings (Table 4). Subjects identified as having VaD according to various diagnostic criteria. definitions of VaD were used among the 107 patients fulfilling the DSM-III criteria for dementia: 36.4% (n 39) by DSM-III, 86.9% (n 93) by ADDTC, 32.7% (n 35) by NINDS-AIREN, 36.4% (n 39) by ICD-10, 91.6% (n 98) by DSM-IV criteria (Tables 1 2). The DSM-III the ICD-10 criteria for VaD had a concordance of 100%. The requirements of these criteria are detailed in Table 2. The ADDTC criteria for the diagnosis of probable ischemic VaD the NINDS-AIREN criteria for probable VaD are also shown in Table 2, as are the DSM-IV criteria. A total of 5 subjects did not fulfill the definition of vascular cause for VaD according to any of the 5 diagnostic criteria, only 31 subjects were diagnosed by all 5 criteria (Figure, Table 3). The concordance (percentage of overlapping cases) between the definitions varied (Table 4): it was excellent between DSM-III ICD-10 criteria (100%), good between ICD-10 NINDS-AIREN criteria (85.0%) between DSM-IV ADDTC criteria (87.3%), but poor between the other criteria ( 40%). Agreement between the guidelines was also calculated by the statistic, which indicates how much better the agreement is than by chance. The agreement was excellent between DSM-III ICD-10 criteria ( 1.0), good between ICD-10 NINDS-AIREN criteria ( 0.87), fair or poor between the other criteria, being at the level of chance between the ICD-10 ADDTC criteria ( 0.03) (Table 4). TABLE 3. Agreement on the Diagnosis of a Vascular Cause of Dementia According to Various Clinical Criteria in Patients With DSM-III Poststroke Dementia (n 107) in the Helsinki Stroke Aging Memory Study Cohort Discussion We evaluated the effect of different definitions of vascular cause in current clinical criteria for VaD in a series of 107 patients with DSM-III poststroke dementia. Different definitions for VaD gave different frequency estimates, overlap in the cases diagnosed was considerable, except between the ICD-10 DSM-III criteria, where it was perfect. The origins of these differences include the following: (1) requirement of focal neurological signs symptoms to be present in DSM-III, ICD-10, NINDS-AIREN criteria; (2) absence of brain imaging requirements of relevant cerebrovascular disease (CVD) in DSM-III, ICD-10, DSM-IV criteria; (3) requirement of patchy or unequal distribution of higher cognitive functions in DSM-III ICD-10 criteria. Additional factors include (4) qualifying extensive white matter lesions as radiological evidence of relevant CVD in NINDS-AIREN but not in ADDTC criteria (5) requiring one CT or T1-weighted MRI infarct outside the cerebellum in ADDTC criteria. The DSM-III ICD-10 criteria had a concordance of 100%. Neither of these guidelines specifies brain imaging requirements. They require evidence from history, physical examination, or laboratory tests of significant CVD that is judged to be etiologically related to the disturbance. They also require focal neurological signs symptoms on neurological examination to be present require unequal distribution of cognitive deficits. We did not study possible ICD-10 subtypes of VaD in the present study. 22 The agreement between NINDS-AIREN ICD-10 was good (concordance, 85%; weighted 0.87), as well. They both require focal neurological signs to be present, which were infrequent in the present patients with a history of ischemic stroke. The main origin of difference between these 2 criteria is requirement of unequal distribution of deficits in higher cognitive functions by ICD-10 detailed radiological criteria by NINDS-AIREN. No Vascular Cause NINDS-AIREN DSM-IV DSM-III/ICD-10 ADDTC No vascular cause 5 72 9 68 14 NINDS-AIREN 72 35 35 34 32 DSM-IV 9 35 98 39 89 DSM-III/ICD-10 68 34 39 39 33 ADDTC 14 32 89 33 93

2956 Stroke December 2000 TABLE 4. Concordance Between Various Clinical Criteria for the Diagnosis of Vascular Cause of VaD in Patients With DSM-III Poststroke Dementia (n 107) in the Helsinki Stroke Aging Memory Study Cohort Applied Criteria Concordance Discriminating Factors NINDS-AIREN/DSM-IV 35.7% 0.08 Focal neurological signs /or laboratory evidence of CVD NINDS-AIREN/ICD-10 DSM-III 85.0% 0.87 Unequal distribution of deficits in higher cognitive functions, evidence of relevant CVD in MRI NINDS-AIREN/ADDTC 33.3% 0.05 Focal neurological signs DSM-IV/ICD-10 DSM-III 39.8% 0.09 Focal neurological signs /or laboratory evidence of CVD DSM-IV/ADDTC 87.3% 0.37 Focal neurological signs /or laboratory evidence of CVD ICD-10 DSM-III/ADDTC 33.3% 0.03 Focal neurological signs In addition to the NINDS-AIREN criteria, the other criteria defining the radiological findings are the ADDTC criteria, which require at least 1 infarct outside the cerebellum detected on CT or T1-weighted MRI, but white matter lesions do not qualify for support of probable ischemic VaD. The NINDS-AIREN criteria require focal signs to always be present, the ADDTC criteria require evidence of 2 ischemic strokes by history, neurological signs, /or neuroimaging studies (CT or T1-weighted MRI); accordingly, the agreement between these 2 criteria was poor (concordance, 33%; weighted 0.05). As evaluated neuropathologically, the ADDTC criteria seem to be more sensitive the NINDS-AIREN criteria more specific, but neither is perfect. 23 The DSM-IV criteria were the most liberal; a total of 98 subjects (91.6%) fulfilled these criteria. The DSM-IV criteria do not require focal neurological signs symptoms to be present do not specify brain imaging criteria clearly. In a recent study of 25 demented subjects, the DSM-IV criteria showed the best overall agreement with other criteria for VaD ( range, 0.32 to 0.60) gave the greatest overlap with the combined ADDTC for probable possible ischemic VaD. 6 In the present study the agreement between DSM-IV the other criteria varied to a greater extent (concordance, 33% to 87%; weighted range, 0.08 to 0.37), which related to the frequency of focal neurological signs. In the present cohort, in patients with ischemic stroke, only 40 patients (37.4%) showed focal signs on neurological examination (hemianopia, lower facial weakness, dysarthria, motor or sensory hemisyndrome, hemiplegic gait, or positive Babinski sign) 3 months after stroke. In accordance with our findings, the small percentage of cases classified as VaD depended on the small number of subjects showing focal signs on the neurological examination in the series of Wetterling et al. 5 In particular, patients with small-vessel subcortical VaD frequently do not show clear-cut focal signs. Thus, neuroimaging criteria could increase sensitivity specificity in case finding, 7,24 as suggested in the recent research criteria for subcortical small-vessel VaD. 20 In the DSM-III, ICD-10, DSM-IV criteria, no clear specification of an underlying vascular process is given; the ADDTC criteria are limited to ischemic brain injury, the NINDS-AIREN criteria compile a description of many possible etiologies of VaD. Thus, it is not surprising that the concepts underlying the definitions of vascular cause are rather heterogeneous, with agreement at the level of chance (between the ADDTC ICD-10 criteria, 0.03). In conclusion, the clinical criteria for VaD are not interchangeable. Despite a degree of overall similarity, the case finding will vary significantly depending on the criteria. Our study thus strengthens the earlier findings in a large, welldefined stroke cohort. 4,5 Furthermore, we focused only on the vascular cause of dementia in patients already found to be demented. At present, the lack of comparability between diagnostic criteria is a barrier to research clinical care, further debate based on these earlier findings is needed. The differences we found will influence not only estimates of prevalence incidence of VaD but also clinical recognition treatment of the condition. 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