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.     

Clinicopathological investigation of vascular parkinsonism, including clinical criteria for diagnosis.

Vascular parkinsonism (VP) is difficult to diagnose with any degree of clinical certainty. We investigated the importance of macroscopic cerebral infarcts and pathological findings associated with microscopic "small vessel disease" (SVD) in the aetiology of VP. The severity of microscopic SVD pathology (perivascular pallor, gliosis, hyaline thickening, and enlargement of perivascular spaces) and the presence of macroscopically visible infarcts were assessed in 17 patients with parkinsonism and no pathological evidence of either Parkinson's disease or any histopathological condition known to be associated with a parkinsonian syndrome, and compared with age-matched controls. Microscopic SVD pathology was significantly more severe in the parkinsonian brains. Most patients presented with bilateral bradykinesia and rigidity together with a gait disorder characterised predominantly by a shuffling gait. Four patients presented acutely with hemiparesis and then progressed to develop a parkinsonian syndrome. They could be distinguished from the remaining VP patients by the presence at autopsy of macroscopically visible lacunar infarcts in regions where contralateral thalamocortical drive might be reduced. The clinical features at presentation varied according to the speed of onset and the underlying vascular pathological state. New clinical criteria for a diagnosis of VP are proposed based on the clinicopathological findings of this study.     

Accuracy of four clinical diagnostic criteria for the diagnosis of neurodegenerative dementias.

OBJECTIVE: To evaluate the inter-rater reliability and validity of clinical diagnostic criteria for neurodegenerative dementias. BACKGROUND: Inter-rater accuracy of the diagnosis of AD has been explored, but there are few accuracy studies for progressive supranuclear palsy (PSP) and frontotemporal lobe dementia (FTD). Furthermore, there have been no simultaneous accuracy studies in a mixed sample of patients with cortical and subcortical neurodegenerative processes. METHODS: Four experienced clinicians reviewed first-visit clinical data abstracted from the records of 40 pathologically diagnosed demented subjects. They were asked to apply the NINCDS-ADRDA criteria for AD, the NINDS-SPSP clinical criteria for PSP, the Lund and Manchester criteria for FTD, and the Consensus Guidelines for the Clinical Diagnosis of Dementia with Lewy Bodies (DLB). Results: The generalized K for AD was 0.73, for PSP 0.82, for FTD 0.75, and for DLB 0.37. The K pool test showed a statistically significant difference between DLB and the other disease processes, and no differences were observed among AD, FTD, and PSP. The mean sensitivity for AD was 95%, for PSP 75%, for FTD 97%, and for DLB 34%. The mean specificity for AD was 79%, for PSP 98.5%, for FTD 97%, and for DLB 94%. CONCLUSIONS: We found improved inter-rater reliability for the diagnosis of AD among clinicians compared with earlier studies. Similarly, there was a near-perfect and substantial inter-rater agreement for the diagnosis of PSP and FTD. The sensitivity for the diagnosis of AD was high, although clinicians overdiagnosed this condition. However, there was a reasonable accuracy for the diagnosis of PSP and FTD. Heterogeneity of the clinical presentation of DLB significantly affected inter-rater agreement and accuracy. The use of multiple diagnostic criteria for cortical and subcortical dementia increases the level of clinical diagnostic accuracy.     

Clinical criteria for psychiatric diagnosis and DSM-III.

The authors identify the differences in formal inclusion and exclusion criteria used to classify patient data into diagnoses as the largest source of diagnostic unreliability in psychiatry. They describe the efforts that have been made to reduce these differences, particularly the specified criteria approach to defining diagnostic categories, which was developed for research purposes. On the basis of studies showing that the use of specified criteria increases the reliability of diagnostic judgments, they suggest that including such criteria in the next edition of APA's Diagnostic and Statistical Manual of Mental Disorders (DSM-III) would improve the reliability and validity of routine psychiatric diagnosis.     

Electrodiagnostic criteria for diagnosis of ALS.

A consensus meeting was held to determine the best use and interpretation of electrophysiological data in the diagnosis of ALS. The utility of needle EMG and nerve conduction studies was affirmed. It is recommended that electrophysiological evidence for chronic neurogenic change should be taken as equivalent to clinical information in the recognition of involvement of individual muscles in a limb. In addition, in the context of a suspected clinical diagnosis of ALS, fasciculation potentials should be taken as equivalent to fibrillation potentials and positive sharp waves in recognising denervation. The importance of searching for instability in fasciculation potentials and in motor unit potentials in ALS is stressed. These changes in the interpretation of electrophysiological data render obsolete the category Probable Laboratory-Supported ALS in the modified El Escorial diagnostic criteria for ALS. Methods for detection of upper motor neuron abnormality appear sensitive but require further study, particularly regarding their value when clinical signs of upper motor neuron lesion are uncertain.     

Reliability of clinical criteria for the diagnosis of dementia. A longitudinal multicenter study

The reliability of the clinical diagnosis of dementia was estimated by comparing the diagnosis made at 1-year intervals on 55 consecutive subjects with suspected cognitive impairment seen at three different centers by neurologists and gerontologists. The diagnosis was based on history and clinical examination, the criteria of the Diagnostic and Statistical Manual of Mental Disorders (revised ed 3), the Modified Ischemic Score, and a computed tomographic scan. Fifty-two of 55 subjects were given the same diagnosis a year later indicating a reliability of 95%. The study shows that a diagnosis of dementia established by simple clinical criteria comparable to the NINCDS/ADRDA criteria affords sufficient reliability to allow the comparability of groups at different centers for purposes of research, including research on the evaluation of the efficacy of pharmacologic treatment.     

Reliability of NINCDS-ADRDA clinical criteria for the diagnosis of Alzheimer's disease

Although the NINCDS-ADRDA Work Group has recently developed uniform clinical criteria for the diagnosis of Alzheimer's disease (AD), inter-rater reliability studies of these criteria are few. We report a study in which 2 neurologists and 2 psychiatrists independently reviewed clinical data abstracted from the records of 30 demented subjects and 10 nondemented control subjects participating in a longitudinal study of AD at the University of Pittsburgh. We recorded the clinical data on a standardized form; the subjects' identity and clinical and pathologic diagnoses were omitted. Each physician diagnosed each case according to the NINCDS-ADRDA criteria. We calculated the inter-rater agreement for all possible 2-way combinations of clinicians with the Kappa statistic, which ranged from 0.36 (fair agreement) to 0.65 (substantial agreement). We conclude that current NINCDS-ADRDA criteria enable moderate levels of agreement among clinicians in general.     

The accuracy of clinical criteria for the diagnosis of frontotemporal dementia

The clinical diagnosis of frontotemporal dementia (FTD) can be challenging even to experienced clinicians. In the absence of a definitive clinical test, this diagnosis relies on behavioral criteria. Difficulty applying these criteria arise for four main reasons. First, FTD patients present with social and personality changes that defy the neuropsychological model of dementia. Second, FTD is not a single disorder but a spectrum of clinical syndromes with asymmetric and motor variants. Third, there may be qualitatively different symptoms during stages of FTD. Finally, pathologic and genetic variability contributes to the clinical variability. Future research should refine the clinical criteria for FTD using clinicopathological correlation in addition to working on the development of neurobiological markers.     

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.     

Diagnosis of Angelman syndrome: clinical and EEG criteria.

In order to evaluate which diagnostic criteria can be indicative for an early diagnosis of Angelman syndrome (AS), 144 children with severe epilepsy and mental retardation were evaluated. In 10 of them the diagnostic criteria indicated by Williams were present. Of the remaining 134 patients we were able to diagnose one 15-year-old patient with AS, on the basis of the EEG findings, even though the typical clinical features of the syndrome were absent. In all patients the diagnosis of AS was confirmed by fluorescent in situ hybridization (FISH) in 10 patients and by methylation analysis in one patient. AS is very likely when both typical clinical and EEG findings are present. Nevertheless, it must be considered in all patients affected by severe epilepsy and mental retardation, when the EEG pattern is sufficiently indicative, and FISH and/or molecular analysis should be performed even in absence of typical clinical signs.     

Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria

The NINCDS-ADRDA and the DSM-IV-TR criteria for Alzheimer's disease (AD) are the prevailing diagnostic standards in research; however, they have now fallen behind the unprecedented growth of scientific knowledge. Distinctive and reliable biomarkers of AD are now available through structural MRI, molecular neuroimaging with PET, and cerebrospinal fluid analyses. This progress provides the impetus for our proposal of revised diagnostic criteria for AD. Our framework was developed to capture both the earliest stages, before full-blown dementia, as well as the full spectrum of the illness. These new criteria are centred on a clinical core of early and significant episodic memory impairment. They stipulate that there must also be at least one or more abnormal biomarkers among structural neuroimaging with MRI, molecular neuroimaging with PET, and cerebrospinal fluid analysis of amyloid beta or tau proteins. The timeliness of these criteria is highlighted by the many drugs in development that are directed at changing pathogenesis, particularly at the production and clearance of amyloid beta as well as at the hyperphosphorylation state of tau. Validation studies in existing and prospective cohorts are needed to advance these criteria and optimise their sensitivity, specificity, and accuracy.     

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.     

Accuracy of clinical diagnostic criteria for Friedreich's ataxia.

The accuracy of the diagnostic criteria for Friedreich's ataxia proposed by Harding and by the Quebec Cooperative Study on Friedreich's Ataxia was studied in 142 patients with progressive unremitting ataxia of autosomal recessive inheritance or sporadic occurrence. Eighty-eight patients received the molecular diagnosis of Friedreich's ataxia. Traditional diagnostic criteria are characterized by high specificity, but they yield a high number of false-negative diagnoses. We suggest three levels of diagnostic certainty: (1) possible Friedreich's ataxia, defined as sporadic or recessive progressive ataxia with (a) lower limb areflexia and dysarthria, Babinski sign, or electrocardiographic repolarization abnormalities, or (b) with lower limb retained reflexes and electrocardiographic repolarization abnormalities (95% sensitivity and 88% positive predictive value); (2) probable Friedreich's ataxia as defined by Harding's criteria (63% sensitivity and 96% positive predictive value) or by Quebec Cooperative Study on Friedreich's Ataxia criteria (63% sensitivity and 98% positive predictive value); (3) definite diagnosis, molecularly confirmed.     

Sensitivity and specificity of three clinical criteria for dementia with Lewy bodies in an autopsy-verified sample.

OBJECTIVE: To evaluate the sensitivity and specificity of the clinical features of three published diagnostic criteria for diffuse Lewy body disease (DLBD) using autopsy-confirmed Alzheimer's (AD), DLBD and AD+DLBD (mixed) dementia cases. DESIGN: Retrospective chart review of an autopsy series of 56 patients selected from the State of Florida Brain Bank on the basis of a pathological diagnosis of either pure AD, DLBD (pure and common forms) or AD+DLBD (mixed) dementia. Clinical features were assessed by three raters blind to the pathological diagnosis. RESULTS: The existing criteria for a clinical diagnosis of DLBD were highly specific (90-100%) but not very sensitive (49-63%) in the differential diagnosis of DLBD versus AD; sensitivity did improve (61-74%) when mixed AD+DLBD cases were eliminated. Clinical features that occur more frequently in DLBD than in AD were unspecified hallucinations, unspecified EPS, fluctuating course and rapid progression. Post-hoc analysis also indicated that hallucinations and EPS were more common early in the disease course of DLBD than in AD. Empirically derived criteria, formulated using the most prevalent clinical features, demonstrated sensitivity values of 57-96% for pure forms and 43-91% for mixed forms. CONCLUSIONS: This study demonstrated that additional improvements in the established criteria for DLBD are needed. Our empirically derived criteria enhanced the distinction of DLBD from AD while allowing the clinician the choice of maximizing sensitivity with acceptable specificity, and vice versa.