Accurate and early diagnosis of Alzheimer's disease (AD) is vital to ensure patients receive the proper treatment, research is targeted correctly, and prevention and cures are found. However, it can be difficult to distinguish between AD and other forms of dementia, or even from other reversible disorders. The Alzheimer's Association has compiled an outline of the 10 most common symptoms associated with AD (Table 1) to help alert patients, caregivers and clinicians so that they can take action at the earliest signs of the disease. The earlier AD is diagnosed, the more treatable it is. The following is a review of some current tools used for diagnosis, and an update on research into promising new techniques for AD assessment.
Standard Assessment Tools
The standard tools for assessing AD include neuropsychological or cognitive evaluation, physical exam, neurological exam, laboratory testing, neuroimaging, behavioral assessment, and patient history. Many of these tests have been used for several years, and the question has been raised as to which are most effective.
Standard guidelines such as the DSM-III-R and those from the National Institute of Neurologic, Communicative Disorders and Stroke-AD and Related Disorders Association (NINCDS-ADRDA) have proven to be reliable resources for clinicians.
A recent meta-analysis of the diagnostic accuracy of these tests compared to neuropathologic confirmation from several studies revealed that both guidelines achieved an average of 81% sensitivity for a diagnosis of "probable" AD (Knopman et al., 2001). A diagnosis of "possible" AD achieved a very high sensitivity of 93%. Specificity for both diagnoses was lower, at 70% and 48%, respectively.
With respect to neuroimaging, magnetic resonance imaging, computed tomography (CT), single photon emission computed tomography (SPECT) and positron emission tomography (PET) have all been used to assist in the diagnosis of AD. In a study cited by Knopman and colleagues (2001), when compared to neuropathologic confirmation, CT scans were 95% sensitive and 40% specific for diagnosing AD based on the width of the medial temporal lobe in 86 autopsied cases. The researchers also assessed the value of SPECT in two large studies of autopsy-confirmed diagnoses of AD. The SPECT results revealed sensitivities ranging from 86% to 95%, and specificities ranging from 42% to 73% when comparing patients with AD and non-AD dementia. In a smaller study, PET scans were reported to have a sensitivity of 93% and a specificity of 63%. Knopman and colleagues cautioned that imaging should be used in conjunction with other tests to increase the likelihood of an accurate diagnosis. Only noncontrast CT or MRI scans were recommended for use in routine initial evaluation of dementia patients. Neither SPECT nor PET imaging have proven to be superior to clinical criteria for AD.
Cognitive assessment is essential to the diagnosis and treatment of AD. There are several neuropsychological tests to assess the patient's cognition as well as their overall clinical condition. It is also important to measure their function in activities of daily living. Finally, caregiver-based interviews or questionnaires are useful for assessing behavioral disorders. A list of these assessment scales can be found in Table 2.
Genetic (e.g., apoliproprotein E genotyping) and cerebrospinal fluid markers have been used when assessing patients for AD. However, Knopman and colleagues do not recommend using these or other genetic markers to diagnose AD, primarily because clinical criteria are more sensitive. Comorbidities, such as depression, vitamin B12 deficiencies and hypothyroidism, should be evaluated.
One of the greatest challenges of assessing AD is whether the patient's symptoms reflect true AD, some other dementia or a different disorder altogether. The tools previously mentioned can assist in differential diagnosis, but it is important for clinicians to be aware of the subtle differences and characteristics that distinguish AD. The Alzheimer's Association provides a "Differential Diagnosis in AD Algorithm" outlining step-by-step procedures for diagnosing AD. It is available at <www.alz.org/PhysCare/Diagnose/procedure.htm>.
A majority of dementias such as vascular dementia (VaD), frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB) are a result of vascular and degenerative brain diseases (Waldemar et al., 2000). In addition, inflammatory diseases, intra-cranial tumors and normal pressurehydrocephalus are rare symptomatic causes of dementia. According to the Alzheimer's Association, disorders that are associated with "reversible" dementia include depression, medication-induced dementia, hypothyroidism, B12 deficiency and systemic infections.
Lack of personal concern, disinhibition, indifference, compulsion and repetitive stereotyped behaviors demonstrate particular behaviors of FTD but are not typically seen in AD (Waldemar et al., 2000). Waldemar and colleagues also noted that early symptoms of DLB can include delusions and hallucinations. According to the Alzheimer's Association, VaD differs from AD in that the cognitive changes are typically associated with an onset within three months following a stroke, abrupt deterioration in cognitive functions or fluctuating, stepwise progression of cognitive deficit. Depression in elderly patients can manifest itself as confusion, memory disturbance and impaired attention, all of which are typically not seen in younger depressed patients. Alzheimer's disease may also coexist with depression, with each disorder exacerbating the other.
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