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KCE Reports 111 Interventions in Alzheimer’s Disease 9
2 SCREENING, DIAGNOSIS AND STAGING
2.1 SEARCH
First, relevant HTA reports were searched in the HTA database of the Centre for
Reviews and Dissemination (CRD). Second, a search was done for systematic reviews
(using the Cochrane Database, DARE, and Medline) focusing on Alzheimer disease.
HTA reports and systematic reviews were identified June 5, 2008 using “Alzheimer” as
keyword for searching the databases HTA at CRD and DARE at CRD, and searching
PubMed (Medline) using ("Alzheimer Disease/diagnosis"[Mesh] OR "Alzheimer
Disease/drug
systematic[sb]
therapy"[Mesh] OR "Alzheimer Disease/therapy"[Mesh]) AND
2.2
We selected HTA reports and systematic reviews which minimally covered the
literature published up to mid 2004 or which were found to be of particular relevance.
The identified studies were selected based on title and abstract. We did not perform
any formal scoring of the quality of the reviews, which can be considered a limitation of
the study.
THE DIAGNOSTIC PROCESS
Compared with AD therapy, fewer systematic reviews were identified covering the
diagnostic process. SBU performed a systematic review on this subject 14 (publications
covered until June 2004) and also an EFNS task force reviewed the literature 13
(publications covered until January 2006). Also the dementia practice guidelines by
NICE-SCIE 1 were considered.
SBU 14 classified evidence into evidence grade 1 or strong evidence, evidence grade 2 or
moderately strong evidence, evidence grade 3 or limited evidence, and no evidence. The
classification also took into account whether all or most of the studies met the general
criteria (sensitivity >80%, specificity > 80% and a likelihood ratio (LR+) >=5 for tests
used to diagnose dementia). The EFNS task force also graded the recommendations
according to decreasing strength of evidence into grade A, B, or C. 13
SBU concluded there are no diagnostic instruments sufficiently developed to be used for
dementia screening. 14 A gold standard is lacking for identifying dementia and ruling out
other syndromes. Many methods (scales and indices) are used to measure the severity
of various symptoms of dementia, such as cognitive deterioration, functional decline and
behavioural changes. The insufficient evaluation to which most methods have been
subjected makes it more difficult to assess the efficacy of specific care and treatment
approaches. 14
An initial selection or screening of patients for possible further diagnosis can be made
by general practitioners and be based on standardised interviews with collateral
sources, such as informal or family caregivers (Evidence Grade 2), as well as simple tests
such as the MMSE, the clock drawing test and other simple tests (Evidence Grade 2). 14
Such initial selection by GPs is to be distinguished from diagnosis and is considered
more difficult in mild AD and in MCI compared with more advanced disease. Potential
limitations, particularly of the MMSE, include associations with education level and
sensitivity to depression. 1 In patients for whom the MMSE is not an appropriate tool, an
assessment tool sensitive to their level of competence should be used. 1
SBU concludes that after a baseline assessment, detection of atrophy of the medial
temporal lobe by computer tomography (CT scan) and magnetic resonance imaging
(MRI scan), respectively can identify people who have Alzheimer’s disease with a high
degree of certainty (Evidence Grade 1). 14 Experts agree with this statement at group
level but consider the sensitivity may be too low at the individual level. Recently, based
on structural MRI, medial temporal lobe atrophy was also found to distinquish probable
AD from mild cognitive impairment. 15 Volumetric MR techniques are however very time
consuming to apply in clinical practice. 1