Clinicopathological validation study of four sets of clinical criteria for vascular dementia.

OBJECTIVE: The authors' goal was to validate the clinical criteria for vascular dementia of the State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC), the National Institute for Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN), DSM-IV, and ICD-10. METHOD: Sensitivity and specificity were assessed by comparing the clinical with the neuropathological diagnosis of 89 autopsied patients with dementia from a geriatric and psychiatric hospital. All cases were reviewed by a clinician and a neuropathologist who were blind to each other's findings. RESULTS: Neuropathologically there were 20 cases of vascular dementia, 23 cases of mixed dementia, and 46 cases of Alzheimer's disease among the autopsied patients. The sensitivity was 0.50 for DSM-IV criteria for vascular dementia, 0.70 for ADDTC criteria for possible vascular dementia, 0.55 for NINDS-AIREN criteria for possible vascular dementia, 0.20 for ICD-10 criteria for vascular dementia, 0.25 for ADDTC criteria for probable vascular dementia, and 0.20 for NINDS-AIREN criteria for probable vascular dementia. Specificity was 0.84, 0.78, 0.84, 0.94, 0.91, and 0.93, respectively. The proportion of cases clinically classified as vascular dementia ranged from 0% to 13% for neuropathologically confirmed cases of Alzheimer's disease and 9% to 39% for neuropathologically confirmed cases of mixed dementia. There was no statistically significant relationship between the neuropathological diagnosis and three of the clinical criteria sets studied (ICD-10 criteria for vascular dementia and ADDTC and NINDS-AIREN criteria for probable vascular dementia). CONCLUSIONS: Clinical criteria for vascular dementia are not interchangeable. The ADDTC criteria for possible vascular dementia are the most sensitive for the detection of vascular dementia; however, the DSM-IV criteria for vascular dementia and the NINDS-AIREN criteria for possible vascular dementia may be more effective in excluding mixed dementia. Given their inability to detect the vast majority of cases of vascular dementia, the ICD-10 criteria for vascular dementia and the ADDTC and NINDS-AIREN criteria for probable vascular dementia should be revised.     

Vascular cognitive impairment

Cognitive impairment commonly accompanies clinical syndromes associated with vascular disease of the brain. Because of evolving definitional criteria, however, the frequency of cognitive impairment attributable to cerebrovascular disease is difficult to determine. Dementia occurs in up to one-third of elderly patients with stroke, a subset of whom have Alzheimer's disease (AD) rather than a pure vascular dementia syndrome. In fact, pure vascular dementia has been shown to be uncommon in most large autopsy series. A mixed etiology of AD and cerebrovascular disease is thought to become more common with increasing age, although no clinical criteria for the diagnosis of AD with cerebrovascular disease are currently available. Epidemiological studies have implicated subcortical small-vessel disease as a risk factor for cognitive impairment and dementia, but the cognitive expression and clinical significance of MRI white matter changes in individual patients is difficult to establish. The frequency of specific neuropathologic features of vascular cognitive impairment depends largely on study inclusion criteria. Cerebral meningocortical microangiopathies with distinctive clinicopathological profiles are associated with dementia in both sporadic cases and familial syndromes. In patients with AD, the contribution of amyloid-beta protein to the degree of cognitive impairment has not been clearly defined.     

Alzheimer's disease and brain infarcts in the elderly. Agreement with neuropathology

Clarifying the etiology of dementia is one of the most difficult diagnostic challenges, especially in the elderly. We examined the accuracy of clinical criteria to distinguish Alzheimer's disease (AD) and dementia associated with infarcts of the brain, either isolated (vascular dementia) or associated with degenerative lesions (mixed dementia). We carried out a prospective clinico-neuropathological study in a selected series of hospitalized patients. We evaluated the clinical aspects of 33 patients aged over 75 years by use of the criteria and scores of DSMIII, NINCDS-ADRDA, Loeb and Gandolfo, ADDTC and NINDS-AIREN and the Hachinski Ischemic Score. The neuropathological diagnosis was considered to be the gold standard. When comparing clinical criteria and neuropathology, the agreement was moderate for Hachinski's score (0.50) and Loeb's score (0.43) and substantial for the ADDTC (0.63) and the NINDS-AIREN (0.67). When mixed dementias were excluded, the agreement between all clinical criteria and scores and the pathological diagnosis rose to 0.88. Hachinski's score was the most sensitive (0.89) and the NINDS-AIREN the most specific (0.86) for the diagnosis of vascular dementia. In conclusion, all sets of clinical criteria distinguished pure AD from vascular dementia with a high accuracy whereas mixed dementia was clinically under-recognized. The NINDS-AIREN criteria were the most discriminating for the accurate identification of patients with mixed dementia. Received: 17 November 2001, Received in revised form: 14 May 2002, Accepted: 22 May 2002 Correspondence to Pr. Jean-Jacques Hauw     

CT brain findings in clinical dementia investigation--underestimation of mixed dementia

Dementia has been found to display a more heterogeneous clinical picture than previously recognized. We investigated brain changes on computed tomography (CT) in a clinical dementia population consisting of 67 cases with Alzheimer's disease (AD), 13 with mixed dementia (AD and vascular dementia, VaD), 71 with VaD, and 12 cases that were not demented. Temporal cortical atrophy and atrophy around the temporal horns were more common in patients with mixed dementia compared to patients with VaD and the non-demented, respectively. Frontal white matter changes were present in 64% of AD, in 85% of mixed dementia and in 79% of VaD cases, but there were no differences between the dementia groups. Lacunes were present in almost 40% of AD cases and in 80 and 85% of VaD and mixed dementia cases, respectively. Only 14% of the VaD cases had large infarcts on the CT. We conclude that large infarcts were rare, even in VaD cases. The increased incidence of white matter changes and lacunes in AD patients strongly indicates an underestimation of the mixed dementia diagnosis. More distinct criteria for this diagnostic category are warranted.     

Recent clinical-pathologic research on the causes of dementia in late life: update from the Honolulu-Asia Aging Study

In this study, we compare neuropathological findings at autopsy with clinical dementia diagnoses, such as Alzheimer's disease and vascular dementia. Participants consisted of 363 aged Japanese-American men from the Honolulu-Asia Aging Study. Results indicated that the correspondence between clinical and neuropathologic diagnosis was not great, with 56% of patients diagnosed with probable or possible Alzheimer's disease during life but with only 19% having neuritic plaques and/or neurofibrillary tangles as the sole or dominant dementia-related lesions in the brain at autopsy. Although 16% of cases were attributed to mixed causes during life, almost 40% were found to have significant mixtures of dementia-related lesions at autopsy. Finally, both Alzheimer's disease and non-Alzheimer's disease neuropathologic lesions contributed independently to the explanation of variance on a test of overall cognitive performance. The results suggest that clinical diagnosis of dementia made during life may fail to reflect the pathogenic complexity of this condition in very elderly persons.     

Vascular dementias

Cerebrovascular disorders are the second most frequent cause of dementia in late life next to Alzheimer's disease. A recent community-based autopsy study has demonstrated that relevant cerebrovascular changes are much more prevalent in individuals aged 70+ years than previously assumed. Furthermore, the combination between cerebrovascular lesions and Alzheimer-type pathology is the most common neuropathological finding in elderly patients with dementia. There is still some uncertainty about which types of cerebrovascular changes are most likely to cause cognitive impairment including dementia and which pathogenetic mechanisms are involved. Without doubt, however, the vascular dementias are a heterogeneous group of diseases in terms of etiology, histopathology, and clinical appearance. According to the vessel calibres and perfusion territories that are preferentially affected a distinction is commonly made between the frequent subcortical small-vessel disease and the rare cortical large-vessel disease. With these morphological subtypes three major clinical variants are associated: dementia due to subcortical lacunes and white matter changes including Binswanger's disease, multi-infarct-dementia, and dementia due to singular strategic infarcts. In most cases of dementia of cerebrovascular origin the pattern of intellectual impairment is frontal or subcortical, in contrast to the typical cortical presentation of Alzheimer's disease. Deterioration of executive function and attention as well as changes in personality, rather than memory loss, are the predominant symptoms. Therefore the current diagnostic criteria for dementia are poorly suited for the detection of vascular dementias. None of the criteria that have been specifically proposed for the diagnosis of vascular dementias provide clear guidelines for evaluating the causal relationship between cerebrovascular lesions and psychopathological findings. Further research will reveal whether clinical diagnosis can be improved by taking into account the heterogeneity of cerebrovascular diseases. A large proportion of dementias of cerebrovascular origin may be preventable by treating the risk-factors for stroke. Once significant cognitive impairment has occurred, however, there is no established pharmacological treatment for the vascular dementias to date. Only recently results of placebo-controlled clinical trials have become available showing that cholinergic treatment strategies are effective in vascular dementia and in dementia due to combined vascular and neurodegenerative pathologies.     

Prospective neuropathological validation of Hachinski''s Ischaemic Score in dementias.

The sensitivity and specificity of Hachinski's Ischaemic Score (IS) in the diagnosis of the vascular aetiology of dementia was studied in a series of 32 demented patients, dementia of the Alzheimer type (16), multi-infarct dementia (7), mixed dementia (6), Pick's disease (3), with neuropathological diagnosis as the point of reference. The IS distinguished between primary degenerative dementia and multi-infarct or mixed dementia. As single features of the IS "a positive history of stroke" and "a fluctuating course" showed differing prevalences in the latter two diagnostic categories. The IS labelled 21% of patients with primary degenerative dementia as having a vascular aetiology. The uncritical application of the IS to large samples in epidemiological studies may cause incorrect labelling of a significant proportion of patients with primary degenerative dementia as vascular dementia. These results are based on observations of long-term inpatients and depend on neuropathological criteria. While the definite diagnosis of DAT by threshold criteria concerning plaque and tangle counts is well established, neither clinical nor pathological evidence of stroke necessarily means that cerebrovascular disease has anything to do with a patient's dementia.     

Rethinking the dementia diagnoses in a population-based study: what is Alzheimer's disease and what is vascular dementia?. A study from the kungsholmen project

OBJECTIVE: To explore the hypothesis that older adults often are affected by more than one disease, making the differential diagnosis between Alzheimer's disease (AD) and vascular dementia (VaD) difficult. METHODS: Incident dementia cases (n = 308) from a population-based longitudinal study of people 75+ years were investigated. The DSM-III-R criteria were used for the clinical diagnosis of dementia. Data on vascular disorders (hypertension, cerebrovascular and ischemic heart diseases, heart failure, atrial fibrillation, diabetes) as well as type of onset/course of dementia were used retrospectively to reclassify dementias. RESULTS: Only 47% of the AD cases were reclassified as pure AD without any vascular disorder. Among subjects with AD and with a vascular component, cerebrovascular disease was the most common (41%). Only 25% of VaD were reclassified as pure VaD. Further, 26% of the pure AD subjects developed a vascular disorder in the following 3 years. CONCLUSIONS: Both vascular and degenerative mechanisms may often contribute to the expression of dementia among the elderly. Most of the AD cases have vascular involvements, and pure dementia types in very old subjects constitute only a minority of dementia cases.     

Dementia in Saudi Arabia: experience from a university hospital

Objectives - To describe the pattern of presentation, the types of dementia and the associated conditions in Saudi patients. Materials and methods -Hospital-based study using DSM-IV and ICD 10 criteria for consensus diagnosis of cases from clinical information and results of investigations. Dementia subtypes were made according to NINCDS-ADRDA, NINDS-AIREN and ICD 10 criteria while CDR was used for severity grading. Results - A total of 77 demented patients (49 males, 28 females) were studied. The hospital frequency was 19.3/100,000 patients. The mean age at presentation was 74.6 years and age at onset was below 65 years in 17 patients. The types of dementia were: Alzheimer's disease (51.9%), vascular dementia (18.2%), mixed cases (15.6%), dementia with Parkinson's disease (7.8%) and treatable dementia (5.2%). Only 3 patients were in the severe clinical stage and infections were important causes of deterioration. Conclusion - The hospital frequency appears to be low probably because of the relatively young population. The pattern of dementia with preponderance of AD is similar to that in western countries and intervention directed at the risk factors for stroke could reduce the burden of vascular dementia.     

Epidemiology: identifying vascular cognitive impairment

There has been a move in recent years to recognize that the most effective treatment for vascular dementia, and for the mixed component of mixed vascular dementia and Alzheimer's disease, lies not in treatment but in prevention. This requires that cases be identified before the onset of vascular damage (a stage termed "brain-at-risk") or, failing this, as soon as possible but certainly before dementia has developed. These early stages are termed vascular cognitive impairment (VCI). No criteria exist for this early stage of cognitive loss due to cerebrovascular disease and relatively little data exist to indicate how such cases might be identified. The data that do exist suggest that many of the traditional "vascular" features of sudden onset and stepwise progression, etc., are not common in VCI and new criteria will be needed to identify cases. This paper summarizes the data that describe the clinical, neuropsychological, and radiological features that are to be expected in VCI.     

Anosmia in dementia is associated with Lewy bodies rather than Alzheimer's pathology

OBJECTIVES: To assess olfactory function of patients with dementia. Odour detection ability is impaired in clinical Parkinson's disease. Evidence of impaired detection in patients with clinically diagnosed Alzheimer's disease is inconsistent. No studies of olfaction have been neuropathologically validated. METHODS: The olfactory function of 92 patients with dementia and 94 controls was assessed using a simple bedside test as part of the Oxford Project To Investigate Memory and Ageing (OPTIMA). Neuropathological assessment was made of cortical Lewy bodies and substantia nigra (SN) cell counts and of Alzheimer's disease in all 92 patients, 22 of whom had SN Lewy bodies and 43 of whom had only Alzheimer's disease. RESULTS: Patients with Lewy bodies were more likely to be anosmic than those with Alzheimer's disease or controls. Patients with Alzheimer's disease were not more likely to be anosmic than controls. Nor was anosmia associated with degree of neurofibrillary tangles, as assessed by Braak stage. Among subjects with Lewy bodies, overall cortical Lewy body scores and Lewy body density in the cingulate were higher in those who were anosmic. Consensus clinical criteria for dementia with Lewy bodies had a sensitivity of 64% and specificity of 89%. In the absence of definite Alzheimer's disease, the criteria had sensitivity of 100%. In patients with definite Alzheimer's disease, anosmia was slightly more sensitive (55%) than the consensus criteria (33%). However, the addition of anosmia to the consensus criteria did not improve their overall performance. CONCLUSION: Dementia with Lewy bodies is associated with impaired odour detection. Misdiagnosis may have accounted for some previous reports of impaired odour detection in Alzheimer's disease. Simple but more sensitive tests of anosmia are required if they are to be clinically useful in identifying patients with dementia with Lewy bodies.     

Defining dementia: clinical criteria for the diagnosis of vascular dementia

The recognition of cerebrovascular disease (CVD) as a contributing factor and a cause of dementia has led to the development of clinical criteria for vascular dementia (VaD). Due to high specificity, the consensus criteria developed by the National Institute for Neurological and Communicative Disorders and Stroke (NINDS)–Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) have been used in controlled clinical trials to select patients with pure VaD. VaD is predominantly a subcortical frontal form of dementia with prominent executive dysfunction. In contrast, the criteria of the NINCDS–Alzheimer's Disease and Related Disorders Association (ADRDA) emphasize memory loss as the main feature to distinguish Alzheimer's disease (AD) from VaD and from other forms of dementia. Moreover, CVD may precipitate the clinical expression of AD. Although no criteria have been created specifically for patients having AD with CVD, the ischemic score, the Informant Questionnaire on Cognitive Decline in the Elderly and a history of prestroke mild cognitive impairment (MCI) may be useful for identifying patients with this mixed form of dementia.     

Specificity of the clinical diagnosis of dementia.

The specificity of anatomo-clinical observations were investigated on 776 out of 982 consecutive persons hospitalized at the University Psychiatric Clinic of Geneva. Discriminant function analysis shows that most of the anatomical classes (no dementia, senile dementia, Alzheimerized senile dementia and Alzheimer's presenile dementia, vascular dementia, combined dementia nnd undefined form of encephalopathy) are at least partially separable (less than 50% overlap). On the basis of anatomical criteria, Alzheimer's presenile dementia is not separable from Alzheimerized senile dementia, and senile dementia is not separable from combined dementia. Differentiation between the anatomical classes is improved by a preliminary analysis based on clinical diagnosis. Senile plaques account for 43.4% of the total variation between the anatomical classes. The coefficient of agreement between anatomical and clinical diagnosis is 0.27, which is highly significant. The diagnosis of senile dementia has a poor specificity, while the diagnosis of senile Alzheimerized dementia has a better one. The diagnosis of combined dementia has to be reserved for cases with a similar intensity of vascular and degenerative changes. Alzheimer's presenile dementia has a distinct dominant hereditary pattern and must be considered a separate entity. The high specificity of the diagnosis of Alzheimer's presenile dementia makes it possible to conduct epidemiologic and genetic surveys based on clinical data.     

血管性痴呆国际诊断标准的解读与比较

在国外研究中比较常用的血管性痴呆诊断标准有多项。这些诊断标准对于痴呆、卒中以及痴呆和卒中的相关性有不同的定义,一些内容存在较大差异。临床病理对照研究显示这些血管性痴呆诊断标准的诊断敏感度均较低;部分临床诊断标准与病理诊断的一致性较差。目前常用的血管性痴呆国际诊断标准不能互换。     

Vaskuläre Demenz

The term vascular dementia refers to dementia syndromes which are caused by hypoxic-ischaemic brain lesions. Lesions found in vascular dementia such as complete and incomplete infarctions, selective necroses, and others are nonspecific. The characteristics and severity of the clinical syndrome are determined by the size and topography of the ischaemic lesions. Among others, age and pre-existing brain atrophy are risk factors for the development of dementia based on vascular lesions. There is a high comorbidity of Alzheimer's disease and vascular dementia. It can be presumed that ischaemic lesions and Alzheimer-like pathological changes exert additive effects in the manifestation of the clinical dementia syndrome. The diagnostic process follows three steps: 1. presence of a dementia syndrome, 2. presence of cerebrovascular disease, 3. evidence for a relationship between 1 and 2. Present diagnostic criteria, such as "International Classification of Diseases" (ICD-10), "National Institute of Neurological Disorders," "Stroke-Associated Internationale pour la Reserche et l'Enseignement en Neurosciences" (NINDS-AIREN), and "Alzheimer's Disease Diagnostic and Treatment Centers" (ADDTC) describe differing constellations and show little congruence. Estimates of the prevalence depend highly on the set of criteria used. Hence, they differ considerably.     

Mixed dementia: Alzheimer's and cerebrovascular disease

"Mixed dementia" is traditionally defined as Alzheimer's disease with cerebrovascular disease (CVD). Because the risks of both neurodegenerative dementias and cerebrovascular disease increase with age, the mixed dementias are likely the most common. In practice, patients with mixed dementia are diagnosed by one of two routes: Either they have evidence of a neurodegenerative dementia and CVD at the outset, or, they have a classical neurodegenerative presentation but are found to have ischemic lesions by neuroimaging. These facts have implications for the development of evidence-based diagnostic criteria.     

Mild cognitive impairment: believe it or not?

Mild cognitive impairment (MCI) was previously defined as a transitional state that can precede dementia, but the condition and the rates of conversion remain controversial. MCI is now the focus of natural history studies, along with Alzheimer's disease (AD) prevention. The objective of our review will be to consider the question of whether MCI is a well enough established entity that it can be a diagnosis in medical practice and a valid target of Alzheimer's prevention therapy. MCI was originally defined by Petersen et al. (1999) as progressive memory loss, prodrome of Alzheimer's disease. More recently MCI has been expanded to other cognitive domains with other potential causes like normal aging, fronto-temporal dementia, and vascular dementia. Despite many consensus conferences, experts cannot agree on critical aspects of the MCI, particularly with respect to its clinical utility. Based on neuropsychological studies, a hippocampal memory profile has been proposed for MCI as prodromal AD. Further research is needed to advance these criteria. We have no doubt, however, that in the future, the diagnosis of AD as disease (not only a dementia syndrome) will be made in the early pre-dementia stage and will be drawn from a combination of neuropsychological, neuro-imaging and CSF biomarkers.     

Neuropathological findings in patients with clinical diagnoses of probable Alzheimer's disease

To assess prospectively the accuracy of standard antemortem clinical diagnostic criteria for Alzheimer's disease, post-mortem examinations were performed on 25 patients who had met DSM-III criteria for primary degenerative dementia and National Institute of Neurological and Communicative Disorders and Stroke criteria for probable Alzheimer's disease. Seventeen patients (68%) met neuropathological criteria for Alzheimer's disease. Two presenile-onset patients had diffuse neocortical senile plaques of insufficient number for definite Alzheimer's disease. Six patients had non-Alzheimer's disease diagnoses. Five of these six had presenile-onset dementia. These results suggest caution in the antemortem diagnosis of Alzheimer's disease in presenile-onset dementia.     

Diagnosis,risk factors,and treatment of vascular dementia

Although the introduction of modern neuroimaging techniques and standardized clinical evaluations has improved the identification of cerebrovascular disease, the clinical diagnosis of vascular dementia (VaD) is still problematic. Neuropathologic studies have found the current clinical criteria for VaD had low sensitivity with high specificity, suggesting that cerebrovascular disease of sufficient severity to cause cognitive deficits is frequently associated with other disease processes (eg, Alzheimer’s disease). The critical factors about the diagnosis of VaD are centered on two issues: definition of dementia and determination of vascular disease. The current clinical criteria for VaD have different definitions of dementia, which are mainly based on an Alzheimer’s disease-like presentation, and severe vascular disease can present with or without history of clinical strokes. Therefore, there is a need for a better definition of VaD. This is extremely important to better understand its risk factors, as well as to create homogenous cohorts suitable for drug trials.