Comparability of the clinical diagnostic criteria for vascular dementia: a critical review. Part I

This review is the first of a two-part series focusing on the comparability of eight clinical criteria used for the diagnosis of vascular dementia: the Hachinski Ischemic Scale; the Ischemic Scale of Rosen; the criteria proposed by the Diagnostic and Statistical Manual of Mental Disorder-Third Edition (DSM-III), DSM-III-R, DSM-IV; International Classification of Diseases, 10th Revision (ICD-10); State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC); and the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN). The authors discuss the critical issues related to the definition of the cognitive syndromes as well as the vascular causes and associated heterogeneity of symptomatology across these criteria.     

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.     

Validity of clinical criteria for the diagnosis of dementia with Lewy bodies

OBJECTIVE: To assess the clinical validity of clinical diagnostic criteria for dementia with Lewy bodies (DLB). METHODS: We assessed the sensitivity, specificity, and positive and negative predictive values of the clinical criteria of the Consortium on dementia with Lewy Bodies (CDLB) in 18 patients with autopsy-proven DLB and in 76 patients with dementia not associated with Lewy bodies, using postmortem diagnosis as a gold standard. RESULTS: CDLB criteria had either high sensitivity or high specificity, but no set of criteria simultaneously provided both high sensitivity and high specificity. Clinical criteria had higher predictive validity in patients with pure DLB than in patients with DLB and AD. Seventy-eight percent of patients with pure DLB had two or more major criteria, compared with 44% of patients with DLB and AD (p<0.02). If the nine patients with DLB and AD were excluded from the DLB group, the CDLB criteria for probable DLB had sensitivity of 78% and specificity of 85%. CDLB criteria for probable DLB (two or more major criteria) distinguished DLB from AD with a sensitivity of 78% and a specificity of 64%. CONCLUSIONS: The proposed CDLB criteria have high negative predictive value and thus do well at excluding patients with DLB. Positive predictive value of 75% can be achieved by a combination of any three major or minor criteria, providing the analysis is confined to patients with mild to moderate dementia. Criteria were most accurate if confined to patients with pure DLB who had mild to moderate dementia.     

Clinical differentiation of primary degenerative and multi-infarct dementia: a critical review of the evidence. Part II: Pathological studies

A critical examination of representative pathological studies published over the past four decades reveals that this literature fails to provide sufficient support for the antemortem differentiation of primary degenerative dementia (PDD) from multi-infarct dementia (MID) on the basis of clinical criteria. Similar conclusions with respect to clinical studies and articles are presented in Part I of this overview. Among the difficulties commonly encountered in the literature are sampling bias, retrospective design, nonblind assessments, inadequate sample size, failure to consider overlap (i.e., mixed cases), absence of pathological verification in the clinical studies and post hoc reasoning. The necessity to assure that one is dealing with a case of PDD as opposed to some other dementing process is self-evident. However, these reviews show that this capability has not been adequately established with respect to the differential diagnosis of PDD and MID; the evidence to date indicates that the clinical diagnosis of MID, in particular, should be made with caution until more conclusive methods become available.     

Alcohol-related dementia: validation of diagnostic criteria.

OBJECTIVE: The authors sought to validate the diagnostic criteria for alcohol-related dementia. METHODS: The sample consisted of veterans consecutively admitted to a 240-bed VA Nursing Home Care Unit. Baseline and follow-up assessments included measures of cognition and functioning. The diagnosis and type of dementia was determined within 2 months of admission by a geropsychiatrist using patient interviews, chart review, and information from a structured collateral interview. Residents were followed for up to 2 years. RESULTS: Data were collected on 192 of the residents, of whom, 158 (82%) were diagnosed with some form of dementia. Alcohol-related dementia (ARD) was diagnosed in 16 residents (10.1%), probable Alzheimer dementia (AD), in 26 (16.5%); vascular dementia (VD), in 46 (29.1); and mixed or dementia of undetermined origin, in 70 (44.3%). Those with ARD were less cognitively impaired and were more often unmarried. Residents with ARD demonstrated a stabilization of both cognition and functional status, whereas those with AD and VD showed a general decline in both cognition and functional status. CONCLUSION: These results serve to validate the diagnostic criteria for ARD and suggest that abstinence may be of clinical value in treating patients with dementia and alcohol dependence. Further research needs to be conducted to confirm the value of abstinence.     

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.     

Clinical criteria for the diagnosis of vascular dementia

The clinical diagnosis of dementia includes medical history, neurological examination, psychiatric interview and dementia scale. The identification of conditions producing dementia can only be achieved by adding to the clinical information the data gathered from ancillary investigations. The usual ancillary diagnostic investigations (biochemical tests, cerebrospinal fluid (CSF), EEG, CT, MRI, angiography) can rather easily identify brain disorders due to tumors, vascular malformations, hematomas, infections, toxins and drugs, deficiency diseases, normal-pressure hydrocephalus, metabolic and endocrine derangements. The differential diagnosis between degenerative and vascular dementia needs laboratory tests such as CSF, EEG, Somatosensory Evoked Potentials, CT (which constitutes a major role in a modified ischemic score) and MRI. The three final diagnostic labels are possible, probable and definite vascular dementia, which include clinical features and laboratory investigations concurrently confirming the diagnosis. If ancillary investigations fail to show multiple infarct lesions or if mixed forms are suspected an unequivocal diagnosis can be made only on histopathological evidence.     

Clinical diagnostic criteria for dementia associated with Parkinson's disease.

Dementia has been increasingly more recognized to be a common feature in patients with Parkinson's disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD-D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD-D. The Task Force members were assigned to sub-committees and performed a systematic review of the literature, based on pre-defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point-prevelance is close to 30%, older age and akinetic-rigid form are associated with higher risk. PD-D is characterized by impairment in attention, memory, executive and visuo-spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body-type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD-D are proposed.     

Validity of clinical diagnosis in dementia: a prospective clinicopathological study.

With neuropathological diagnosis as the point of reference, the accuracy of clinical diagnosis was studied in a series of 58 demented patients. Alzheimer's disease and multi-infarct dementia were recognised with sensitivities and specificities exceeding 70%, whereas combined dementia as a separate group was relatively unreliably diagnosed. The value of Hachinski's Ischaemic Score in differentiating between Alzheimer's disease and vascular dementias was demonstrated. Its performance was to some extent improved by assigning new weights to the items. In a logistic regression model, fluctuating course, nocturnal confusion, and focal neurological symptoms emerged as features with the best discriminating value, and helped to diagnose correctly 89% of the Alzheimer and 71% of the vascular dementia patients.     

The clinical phenomenology of presenile dementia. A critical review of the literature.

The more recent literature addressing the clinical phenomenology of presenile dementia is reviewed. This survey, spanning approximately the past 4 decades and comprising a large number of articles in scientific journals, reveals that reported epidemiological data, symptoms and signs, and results of ancillary tests often vary widely from study to study, especially as regards findings of history and of mental status and neurological examinations. There is considerable indication that diagnostic specificity in presenile dementia in the absence of pathological examination of the brain by tissue biopsy or at autopsy may not be as reliable as is generally thought to be the case. The observed problems with interstudy agreement are discussed and are seen to be due in large measure to methodological inconsistency and nonuniformity. Areas of difficulties in methods are identified and guidelines for subsequent, needed clinical studies are suggested.     

Establishing diagnostic criteria for vascular depression

We have proposed a subtype of vascular depression with two key elements: (1) presence of major depression and (2) presence of cerebrovascular disease on neuroimaging. Future studies are needed to refine these diagnostic criteria. There must be a consensus as to whether requiring major depression criteria is acceptable, or possibly too stringent. There are several methodological issues regarding cerebrovascular disease, including defining severity and thresholds, importance of location and system of assessment. Once agreement is reached on a working diagnosis of vascular depression, researchers will be in a position to estimate prevalence of the disorder, determine conditions that represent risk factors, and examine important outcomes in patients with vascular depression.     

Clinical differentiation of primary degenerative and multi-infarct dementia: a critical review of the evidence. Part I: Clinical studies

For patient care and for research purposes there is an obvious need for a valid and reliable set of clinical criteria to distinguish antemortem between primary degenerative dementia (PDD) and multi-infarct dementia (MID). To this end, specific diagnostic criteria for each have been promulgated in the official nomenclature, and a rating scale devised to differentiate these disorders is in wide use. These efforts suggest a diagnostic capability that is not, however, well supported by the literature. This critical analysis of representative clinical studies and articles published over the past two decades reveals important drawbacks in methodologic approaches and interpretation of data which seriously undermine confidence in making the clinical distinction between PDD and MID.     

Brain hypoperfusion: a critical factor in vascular dementia

Subcortical ischemic vascular dementia is a relatively common form of dementia. Anatomical changes of ageing in the brain arteries predispose the elderly to the effects of hypotension. Depending on their circulatory pattern, particular regions of the brain are susceptible to ischemic hypoperfusive lesions. These regions include the periventricular white matter, basal ganglia, and hippocampus. Interruption of prefrontal-basal ganglia circuits important for cognition and memory may result from these lesions. Hypotension and hypoperfusion explain the high risk for the development of cognitive impairment and vascular dementia in older patients affected by orthostatic hypotension, congestive heart failure, as well as in those undergoing surgical procedures such as hip and knee replacement and coronary artery bypass graft (CABG). Recognition of the susceptibility of elderly subjects to cerebral lesions induced by hypoperfusion should result in appropriate preventive measures and better treatment.     

CADASIL: a review with proposed diagnostic criteria

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be considered as a new disease predominantly affecting the small vessels of the brain with an autosomal dominant transmission linked to chromosome 19. This review includes an historical perspective showing how the disease was identified from the spectrum of vascular leukoencephalopathies. More than two hundred patients have now been described, belonging to at least 30 unrelated pedigrees in Europe, America and Asia. The clinical features include four major neurological presentations associated in variable degrees during the course of the disease: migraine with or without aura, strokes or stroke-like episodes, major psychiatric symptoms and dementia. The patients are free of the classical vascular risk factors. The disease has a progressive or stepwise course with age at onset in the forties and a mean duration of 13.6 I 10.7 years. Death occurs in the fifties in a characteristic condition associating a pseudo-bulbar syndrome and subcortical dementia. Cerebral magnetic resonance imaging (MRI) is highly contributive to the diagnosis, showing a diffuse leukoencephalopathy with subcortical infarcts in the basal ganglia and white matter. Pathological data show macroscopic lesions similar to Binswanger's disease but different lesions of the small vessels including thickening of the media, characteristic PAS+ granular material and narrowing of the lumen. Skin biopsy may be a valuable diagnostic tool, showing ultrastructural alterations of skin vessels similar to those of brain vessels. The disease is highly homogeneous on a genetic basis and the identification of the gene Notch 3 on chromosome 19 has opened new avenues for research and genetic counselling. The pathogenesis of the disease has still to be elucidated. A definite diagnosis relies on genetical or pathological data. Diagnostic criteria are proposed to recognize the disease on clinical and imaging parameters. So far, no treatment has been reported to be successful for CADASIL.     

Macrocephaly-capillary malformation syndrome: description of a case and review of clinical diagnostic criteria

Macrocephaly-capillary malformation (M-CM) is characterized by prenatal overgrowth, variable somatic and cerebral asymmetry, primary megalencephaly, characteristic facial features, an abnormal neurocognitive profile and cutaneous vascular malformations. It was previously known under the name macrocephaly-cutis marmorata telangiectatica congenital (M-CMTC). However a recent review of the previously reported cases has suggested that the vascular anomalies are not true CMTC but rather capillary malformations. The diagnosis is primary clinical and different criteria have been proposed for this purpose. However, M-CM is frequently associated with structural brain abnormalities that should be properly investigated and monitored because of their possible progressive development. We report the neuroradiological and morphological features observed in a girl with M-CM and we compared them with proposed diagnostic criteria found in the literature.     

Validity of the Short-Memory Questionnaire in vascular dementia

PURPOSE. To determine whether the Short-Memory Questionnaire (SMQ) being administered by caregivers to patients with Alzheimer's disease (AD) is also valid when given to patients with vascular dementia (VaD). METHODS. Subjects were 58 patients with VaD, 26 patients with cerebrovascular disorders free of cognitive deficit (CVD) and 62 healthy controls. All subjects received the Mini-Mental State Examination (MMSE), and their primary caregivers (or family members with same household) received the SMQ. RESULTS. In the VaD patients, the SMQ score was highly correlated with the MMSE score. When 39/40 was defined as a cutoff point based on the results of previous study, the SMQ properly classified 55 of the 58 VaD patients and 61 of the 62 controls, but only about half of the 26 CVD patients, as cases. CONCLUSION. The SMQ, a simple quantitative rating test for memory disturbance, is useful for the assessment and screening of VaD patients as well as AD patients, although careful attention should be paid to the assessment of CVD patients.