Vascular dementia Diagnostic criteria for research studies: Report of the NINDS‐AIREN International Workshop*
TL;DR: These criteria for the diagnosis of vascular dementia are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible).
Abstract: Criteria for the diagnosis of vascular dementia (VaD) that are reliable, valid, and readily applicable in a variety of settings are urgently needed for both clinical and research purposes. To address this need, the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), resulting in research criteria for the diagnosis of VaD. Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features. These criteria are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible). They await testing and validation and will be revised as more information becomes available.
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Johns Hopkins University1, Johns Hopkins University School of Medicine2, Mayo Clinic3, McGill University4, Harvard University5, University of California, Irvine6, University of Pittsburgh7, Columbia University Medical Center8, Eli Lilly and Company9, Washington University in St. Louis10, UCL Institute of Neurology11, VU University Medical Center12, Alzheimer's Association13, Northwestern University14, National Institutes of Health15
TL;DR: The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available.
Abstract: The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.
13,710 citations
TL;DR: The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time.
Abstract: We developed a new instrument, the Neuropsychiatric Inventory (NPI), to assess 10 behavioral disturbances occurring in dementia patients: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability/lability, apathy, and aberrant motor activity. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patient's behavior. Studies reported here demonstrate the content and concurrent validity as well as between-rater, test-retest, and internal consistency reliability; the instrument is both valid and reliable. The NPI has the advantages of evaluating a wider range of psychopathology than existing instruments, soliciting information that may distinguish among different etiologies of dementia, differentiating between severity and frequency of behavioral changes, and minimizing administration time.
6,662 citations
Pierre-and-Marie-Curie University1, University of British Columbia2, University of Pittsburgh3, French Institute of Health and Medical Research4, University of California, Los Angeles5, University of California, San Diego6, McGill University7, University of Kentucky8, Tohoku University9, Brown University10, NewYork–Presbyterian Hospital11, VU University Medical Center12
TL;DR: The NINCDS-ADRDA and 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 as discussed by the authors.
Abstract: 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.
3,951 citations
TL;DR: This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia and provides evidence that subcortical forms of VCI with white matter hyperintensities and small deep infarcts are common and risk markers for VCI are the same as traditional risk factors for stroke.
Abstract: Background and Purpose—This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment ...
2,731 citations
Cites background from "Vascular dementia Diagnostic criter..."
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TL;DR: Elderly people with silent brain infarcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions.
Abstract: BACKGROUND Silent brain infarcts are frequently seen on magnetic resonance imaging (MRI) in healthy elderly people and may be associated with dementia and cognitive decline. METHODS We studied the association between silent brain infarcts and the risk of dementia and cognitive decline in 1015 participants of the prospective, population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia and stroke at base line. Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period. We performed Cox proportional-hazards and multiple linear-regression analyses, adjusted for age, sex, and level of education and for the presence or absence of subcortical atrophy and white-matter lesions. RESULTS During 3697 person-years of follow-up (mean per person, 3.6 years), dementia developed in 30 of the 1015 participants. The presence of silent brain infarcts at base line more than doubled the risk of dementia (hazard ratio, 2.26; 95 percent confidence interval, 1.09 to 4.70). The presence of silent brain infarcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function. Silent thalamic infarcts were associated with a decline in memory performance, and nonthalamic infarcts with a decline in psychomotor speed. When participants with silent brain infarcts at base line were subdivided into those with and those without additional infarcts at follow-up, the decline in cognitive function was restricted to those with additional silent infarcts. CONCLUSIONS Elderly people with silent brain infarcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions.
2,085 citations
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01 Jan 2002
TL;DR: The Mini-Mental State (MMS) as mentioned in this paper is a simplified version of the standard WAIS with eleven questions and requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
Abstract: EXAMINATION of the mental state is essential in evaluating psychiatric patients.1 Many investigators have added quantitative assessment of cognitive performance to the standard examination, and have documented reliability and validity of the several “clinical tests of the sensorium”.2*3 The available batteries are lengthy. For example, WITHERS and HINTON’S test includes 33 questions and requires about 30 min to administer and score. The standard WAIS requires even more time. However, elderly patients, particularly those with delirium or dementia syndromes, cooperate well only for short periods.4 Therefore, we devised a simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely. It is “mini” because it concentrates only on the cognitive aspects of mental functions, and excludes questions concerning mood, abnormal mental experiences and the form of thinking. But within the cognitive realm it is thorough. We have documented the validity and reliability of the MMS when given to 206 patients with dementia syndromes, affective disorder, affective disorder with cognitive impairment “pseudodementia”5T6), mania, schizophrenia, personality disorders, and in 63 normal subjects.
70,887 citations
TL;DR: The unexpected findings in these subjects were higher brain weights and greater number of neurons as compared to age‐matched nursing home control subjects, which suggest people may have had incipient Alzheimer's disease but escaped loss of large neurons, or started with larger brains and more large neurons and thus might be said to have had a greater reserve.
Abstract: Postmortem examination was performed on 137 residents (average age 85.5 years) of a skilled nursing facility whose mental status, memory, and functional status had been evaluated during life. Seventy-eight percent were demented using conservative criteria; 55% had characteristic Alzheimer's disease. Choline acetyltransferase and somatostatin were significantly reduced in the brains of patients with Alzheimer's disease as compared with age-matched nursing home control subjects, although the degree of the reduction was less severe than found in subjects less than 80 years of age. Ten subjects whose functional and cognitive performance was in the upper quintile of the nursing home residents, as good as or better than the performance of the upper quintile of residents without brain pathology (control subjects), showed the pathological features of mild Alzheimer's disease, with many neocortical plaques. Plaque counts were 80% of those of demented patients with Alzheimer's disease. Choline acetyltransferase and somatostatin levels were intermediate between controls and demented patients with Alzheimer's disease. The unexpected findings in these subjects were higher brain weights and greater number of neurons (greater than 90 micron 2 in a cross-sectional area in cerebral cortex) as compared to age-matched nursing home control subjects. These people may have had incipient Alzheimer's disease but escaped loss of large neurons, or alternatively, started with larger brains and more large neurons and thus might be said to have had a greater reserve.
1,163 citations
TL;DR: Criteria for the diagnosis of ischemic vascular dementia (IVD) broaden the conceptualization of vascular dementia, include the results of neuroimaging studies, emphasize the importance of neuropathologic confirmation, refine nosology, and identify areas that require further research.
Abstract: Accurate diagnosis of vascular dementia is important for the recognition of underlying pathophysiology and the institution of appropriate therapy. It is also important for the determination of the incidence and prevalence of not only vascular dementia but also Alzheimer's disease (AD), since differentiating between these two entities is often problematic. The State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) herein propose criteria for the diagnosis of ischemic vascular dementia (IVD). These criteria broaden the conceptualization of vascular dementia, include the results of neuroimaging studies, emphasize the importance of neuropathologic confirmation, refine nosology, and identify areas that require further research. Parallel use of the proposed definitions of "possible" and "mixed" categories in the diagnosis of both AD and IVD would ensure compatibility between the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria for AD and the ADDTC criteria for IVD. Uniform classification of subtypes of IVD will improve the generalizability of individual studies and aid in multicenter collaborations.
1,131 citations
TL;DR: Dr. Rogers’ paper shows that CBF is reduced before there are clinical signs of dementia, and this global reduction in blood flow can be explained by focal areas of ischemia, with diaschisis, or whether there could be a form of “chronic ischemic process.”
Abstract: To the Editor: Dr. Rogers et all demonstrated a decrease in cerebral blood flow (CBF) long before there was clinical evidence of vascular dementia, but CBF was relatively preserved in patients with Alzheimer’s disease and fell only with advancing dementia. I first postulated this difference in 1970’ with the suggestion that in a primary neuronal degeneration, such as Alzheimer’s disease, there is loss of nerve cells due to some cellular abnormality while the blood supply remains intact, so that the flow per unit mass (perfusion rate) might remain constant although the total CBF would fall in parallel with the loss of tissue bulk. However, since CBF is finely adjusted to metabolic demand, and since degenerative processes primarily affect the metabolically more active cells, some reduction in flow proportional to this reduced metabolic demand would occur. In vascular dementia, healthy neurons are imperiled by an inadequate blood supply. In these circumstances, there might first be an increase in arteriovenous oxygen and glucose differences-and this phenomenon has been observed,‘ cell death occurring when this compensatory mechanism fails. Cerebral cortex perfusion rates are likely, therefore, to be reduced early in the disease, and the reduction would be out of proportion to the degree of dementia. This differentiation would occur only early in the disease because long-standing cases of either type are likely to show both a reduced flow and a reduced cell mass, a point confirmed by Rogers et a1.l This hypothesis was tested using the 133-Xenon inhalation technique in 16 patients with the first signs of dementia, 6 with primary neuronal degeneration and 10 with presumably vascular dementia; there was a significant difference between these two groups (23%).’ This study was repeated using the 133-Xenon intracarotid injection technique by Hachinski e t al: with identical results (23%). They took a different view about reasons for the discrepancy, having just published a paper’ postulating that vascular disease caused dementia by a series of large infarcts, and using the term “multi-infarct dementia” (MID). They concluded that the low flow was due to reduced metabolic demand because “an appreciable portion of each 100 grams is infarcted tissue.” Since then, considerable doubt has been expressed about possible contributions to dementia of a chronic ischemic process. PET studies‘, have not shown convincing evidence of neurons that are viable but ischemic and extracting more oxygen and glucose from the available blood than normal. However, there is abundant experimental evidence that ischemic cells may be viable, with a CBF margin of about 10 m1/100 g/min between failure of function and cell death.; Dr. Rogers’ paper shows that CBF is reduced before there are clinical signs of dementia. The question is whether this global reduction in blood flow can be explained by focal areas of ischemia, with diaschisis, or whether there could be a form of “chronic ischemia.” Isolated PET measurements of the oxygen extraction ratios and metabolism over a short time may not be sufficiently sensitive to show a small population of affected cells that might be in this precarious state a t any one time, but which could result in a slow attrition of cells over a long period. The Hachinski index is useful clinically in differentiating MID from Alzheimer’s disease. but the average age of the patients in the series on which this scale was based was only 63,‘ the same as our series.’ Unfortunately, there is a bias that must increase with age, because the index relies on clinical evidence of either relatively large infarcts or small infarcts in eloquent locations and, of necessity, puts all patients without these clinical features into the primary neuronal degeneration group, thereby underestimating the contribution of vascular disease to dementia. In pathologic studies, vascular disease is either the sole cause of dementia or a major contributory factor in 40 to 50% of patientsx ‘I Dr. Rogers’ patients were selected by the presence of risk factors for vascular disease and were a t the time neurologically and mentally normal. Though we do not know whether there might have been CT or MRI evidence of subclinical infarction, it seems unlikely that infarction sufficiently extensive to cause these results could pass unnoticed, 90 why was CBF so low 2 years or more before these patients became demented, with CBF values not significantly greater than either the Alzheimer group or the same patients when they subsequently demented?
1,045 citations