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10 Interventions in Alzheimer’s Disease KCE Reports 111 EFNS recommends non-contrast CT to identify treatable lesions and vascular disease (evidence Level A). In specific situations of differential diagnosis MRI is a more appropriate technique (evidence Level A). 13 SBU concludes that after a baseline assessment, in cases where the diagnosis could not be established by classical methods, biochemical diagnostic markers such as cerebrospinal fluid analysis (Evidence Grade 1) effectively identify (> 80% sensitivity and > 80% specificity) people with Alzheimer’s disease. According to EFNS CSF total tau, phospho-tau and amyloid-beta1-42 can be used as an adjunct in cases of diagnostic doubt (Level B). According to NICE more standardization of CSF tests is required. 1 EFNS recommends cognitive assessment is performed in all patients (level A). SBU concludes that after a baseline assessment, neuropsychological testing (Evidence Grade 1) effectively identifies people with Alzheimer’s disease. A more comprehensive standardised cognitive assessments is particularly useful in patients with with mild or questionable impairment, and in other selected cases to assist with specific subtype diagnosis and differential diagnosis. 1 According to SBU, functional diagnosis – positron emission tomography (PET scan) and single photon emission computed tomography (SPECT scan) – has moderate value (Evidence Grade 2), while neurophysiological testing – EEG brain mapping and quantitative EEG – has limited value (Evidence Grade 3) for identifying dementia disorders. According to EFNS SPECT and PET may be useful in those cases where diagnostic uncertainty remains after clinical and structural imaging work up, and should not be used as the only imaging measure (Level B). 14 FDG PET may show some superiority over perfusion SPECT in detecting AD but remains an expensive and invasive investigation. 1 PET scan tests demonstrating brain amyloid deposits are promising tools and are being used in clinical research studies. 16 These tests were however not yet included in the HTA reports. The Apolipoprotein E (ApoE) e4 allele is known to increase the risk for AD (Evidence Grade 1) but it is a poor marker for identifying Alzheimer’s disease or for differential diagnosis. 14 Definitive diagnosis of AD requires histopathological confirmation of the clinical diagnosis. For research purposes, the diagnosis of AD is given in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV-TR) 17 and the National Institute of Neurological Disorders and Stroke – Alzheimer Disease and Related Disorders (NINCDS-ADRDA) working group. 18 The NINCDS-ADRDA criteria for the clinical diagnosis of probable Alzheimer’s disease have been the reference standard for clinical research studies since 1984. The DSM-IV criteria 17 A. The development of multiple cognitive deficits manifested by both: (1) memory impairment (impaired ability to learn new information or to recall previously learned information) (2) one (or more) of the following cognitive disturbances: (a) aphasia (language disturbance) (b) apraxia (impaired ability to carry out motor activities despite intact motor function) (c) agnosia (failure to recognize or identify objects despite intact sensory function) (d) disturbance in executive functioning (ie, planning, organizing, sequencing, abstracting). B. The cognitive deficits in Criteria A1 and A2 each cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning. C. The course is characterized by gradual onset and continuing cognitive decline. D. The cognitive deficits in Criteria A1 and A2 are not due to any of the following:
KCE Reports 111 Interventions in Alzheimer’s Disease 11 (1) other central nervous system conditions that cause progressive deficits in memory and cognition (eg, cerebrovascular disease, Parkinson’s disease, Huntington’s disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor) (2) systemic conditions that are known to cause dementia (eg, hypothyroidism, vitamin B12 or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection) (3) substance-induced conditions. E. The deficits do not occur exclusively during the course of a delirium. F. The disturbance is not better accounted for by another Axis I disorder (eg, Major Depressive Disorder, Schizophrenia). The NINCDS-ADRDA criteria 18 I. Criteria for the clinical diagnosis of PROBABLE Alzheimer’s disease: • dementia established by clinical examination and documented by the Mini- Mental Test; Blessed Dementia Scale, or some similar examination, and confirmed by neuropsychological tests • deficits in two or more areas of cognition • progressive worsening of memory and other cognitive functions • no disturbance of consciousness • onset between ages 40 and 90, most often after age 65 • absence of systemic disorders or other brain diseases that in and of themselves could account for the progressive deficits in memory and cognition. II. The diagnosis of PROBABLE Alzheimer’s disease is supported by: • progressive deterioration of specific cognitive functions such as language (aphasia), motor skills (apraxia), and perceptions (agnosia) • impaired activities of daily living and altered patterns of behavior • family history of similar disorders, particularly if confirmed neuropathologically • laboratory results of: o normal lumbar puncture as evaluated by standard techniques o normal pattern or non-specific changes in EEG, such as increased slowwave activity o evidence of cerebral atrophy on CT with progression documented by serial observation. III. Other clinical features consistent with the diagnosis of PROBABLE Alzheimer’s disease, after exclusion of causes of dementia other than Alzheimer’s disease, include: • plateaus in the course of progression of the illness • associated symptoms of depression, insomnia, incontinence, delusions, illusions, hallucinations, catastrophic verbal, emotional, or physical outbursts, sexual disorders, and weight loss • other neurologic abnormalities in some patients, especially with more advanced disease and including motor signs such as increased muscle tone, myoclonus, or gait disorder • seizures in advanced disease • CT normal for age. IV. Features that make the diagnosis of PROBABLE Alzheimer’s disease uncertain or unlikely include: • sudden, apoplectic onset
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