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12 Interventions in Alzheimer’s Disease KCE Reports 111
• focal neurologic findings such as hemiparesis, sensory loss, visual field deficits,
and
• incoordination early in the course of the illness
• seizures or gait disturbances at the onset or very early in the course of the
illness.
The sensitivity and specificity of a probable AD diagnosis made according to the
NINCDS-ADRDA criteria with postmortem pathology as reference standard are 0.65
and 0.75. 19 Sensitivity and specificity are generally above 80% when the diagnosis is made
in expert centres and when healthy subjects are used as controls, but are much lower
when patients with other forms of dementia are used as controls. Recently a revision of
these criteria for clinical diagnosis has been proposed, 20 reflecting the increasing
importance of new markers. The criteria were based on a literature review, followed by
an expert meeting in June 2005.
The new proposed criteria for the diagnosis of probable AD consist of the core
diagnostic criterion of early episodic memory impairment (episodic memory is memory
for events that the patient experienced and should be able to recall, more specifically
for recent events) plus one or more of the following supportive features:
• presence of medial temporal lobe (MTL) atrophy on MRI
• abnormal cerebrospinal fluid biomarkers (amyloid beta1-42, total tau, and
phospho-tau)
• a specific pattern on functional neuroimaging with 18F-FDG PET (SPECT
technique did not meet criteria for diagnostic accuracy)
• a proven AD autosomal dominant mutation within the immediate family
The Dubois criteria are very specific and they are currently mainly used in clinical
research studies in order to get validated. Further standardization of these new tests is
needed before their routine use can be considered. 1
In Belgium, reimbursement of medication for AD requires confirmation of the diagnosis
(based on DSM-IV criteria) by a psychiatrist, a neurologist, or a geriatrician specialist in
internal medicine. The care and support team should include the specialist and the
patient general practitioner. Exclusion of other pathology (infarction) is required using a
brain CT or MRI scan. The MMSE score should be in agreement with the indication
approved for the medication class. The functional evaluation should include the 6 points
ADL Katz scale, the instrumental ADL Lawton scale (9 points), as well as the NPI
(Neuro-Psychiatric Inventory) for behaviour. A re-evaluation of the patient after 6
months is required before reimbursement can be prolonged.
Conclusions
There are no diagnostic instruments sufficiently developed to be used for dementia
screening. 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.
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, as well as simple tests such as the MMSE,
the clock drawing test and other simple exercises. 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. Neuropsychological testing is recommended
after a baseline assessment in all patients and is particularly useful in patients with MCI
and mild AD.
The reference standards for the diagnosis of AD are given in the Diagnostic and
Statistical Manual of Mental Disorders, fourth edition (DSM-IV-TR) and the National
Institute of Neurological Disorders and Stroke – Alzheimer Disease and Related
Disorders (NINCDS-ADRDA) working group.