eMedicine Specialties > Neurology > Behavioral Neurology and Dementia

Alzheimer Disease: Differential Diagnoses & Workup

Author: Heather S Anderson, MD, Assistant Professor, Staff Neurologist, Department of Neurology, Alzheimer and Memory Center, University of Kansas Medical Center
Contributor Information and Disclosures

Updated: Aug 27, 2009

Differential Diagnoses

Aphasia
Neurosyphilis
Cortical Basal Ganglionic Degeneration
Parkinson Disease
Dementia in Motor Neuron Disease
Parkinson-Plus Syndromes
Dementia With Lewy Bodies
Prion-Related Diseases
Frontal and Temporal Lobe Dementia
Thyroid Disease
Lyme Disease
Wilson Disease

Workup

Laboratory Studies

  • Laboratory workup can be performed to rule out other conditions that may cause cognitive impairment.
  • Current recommendations from the American Academy of Neurology include measurement of the cobalamin (vitamin B-12) level and a thyroid function screening test. Additional investigations are left to the physician, to be tailored to the particular needs of each patient.
  • Laboratory tests may include the following:
    • Evaluation of the complete blood cell count and cobalamin (vitamin B-12) levels: Abnormalities in these measurements require further workup to rule out hematologic disease.
    • Screening of liver enzyme levels: Abnormalities in these measurements require further workup to rule out hepatic disease.
    • Analysis of thyroid stimulating hormone (TSH) levels: Abnormalities in this measurement require further workup to rule out thyroid disease.
    • Rapid plasma reagent (RPR) test: Abnormalities require further workup to rule out syphilis.

Imaging Studies

  • Brain MRI or CT: In assessing Alzheimer disease, brain MRIs or CT scans are not diagnostic of Alzheimer disease, but can show diffuse cortical and/or cerebral atrophy. In clinical research studies, atrophy of the hippocampi as demonstrated on coronal MRI (structures important in mediating memory processes) is considered a valid biomarker of Alzheimer disease neuropathology. Nonetheless, measurement of hippocampal volume is not used in routine clinical care in the diagnosis of Alzheimer disease. American Academy of Neurology recommendations indicate that structural neuroimaging with MRI or CT is appropriate to detect lesions that may result in cognitive impairment (stroke, small vessel disease, tumor, etc).
  • SPECT or PET scans: Under most circumstances, SPECT or PET scan is not recommended for the routine workup of patients with typical presentations of Alzheimer disease. These modalities may be useful in atypical cases or when some form of frontotemporal dementia is a more likely diagnosis.

Other Tests

  • EEG (see EEG in Dementia and Encephalopathy): EEG is valuable when Creutzfeldt-Jakob disease or other prior-related disease is a likely diagnosis. Periodic high amplitude sharp waves can eventually be detected in most cases of Creutzfeldt-Jakob disease. EEG is also useful if pseudodementia is a realistic consideration when a normal EEG in a patient who appears profoundly demented would support that diagnosis. Multiple unwitnessed seizures rarely can present as dementia and an EEG would be valuable for evaluating that possibility.
  • Lumbar puncture for measurement of CSF tau and amyloid: Tau and phosphorylated tau are often elevated in Alzheimer disease and amyloid is usually low (the reason is not known but perhaps because the amyloid is deposited in the brain rather than the CSF). By measuring both proteins, sensitivity and specificity of at least 80% and more often 90% can be achieved. When effective therapies that slow the rate of progression of Alzheimer disease are developed, lumbar puncture for tau and amyloid may become part of the diagnostic work-up, particularly if the therapies are specific for Alzheimer disease and carry significant morbidity. Until then, routine measurement of CSF tau and amyloid is not recommended, except in research settings.
  • Genotyping for apolipoprotein E alleles: This test is a research tool that is helpful in determining the risk of Alzheimer disease in populations, but it is of little, if any, value in making a clinical diagnosis and developing a management plan in individual patients.
  • Genetic testing for APP and presenilin mutations. After appropriate counseling, such testing is appropriate in early onset cases.
  • In a prospective, randomized, controlled trial, Green et al examined the effect of disclosing apolipoprotein E (APOE) genotyping results to 162 asymptomatic adults who had a parent with Alzheimer disease. Follow-up testing performed 6 weeks, 6 months, and 1 year after disclosure or nondisclosure showed no significant differences between the 2 groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P=0.84), depression (8.8 and 8.7, respectively; P=0.98), or test-related distress (6.9 and 7.5, respectively; P=0.61). Test-related distress was reduced among those who learned that they were APOE epsilon4-negative. Persons who had high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure.16

Procedures

Perform lumbar puncture in select cases to rule out conditions such as normal-pressure hydrocephalus, neurosyphilis, neuroborreliosis, and cryptococcosis.

Histologic Findings

See Pathophysiology for a discussion of the salient histopathologic features of Alzheimer disease.

More on Alzheimer Disease

Overview: Alzheimer Disease
Differential Diagnoses & Workup: Alzheimer Disease
Treatment & Medication: Alzheimer Disease
Follow-up: Alzheimer Disease
References
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Further Reading

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Keywords

Alzheimer’s disease, dementia, cognitive impairment, Alzheimer's disease signs and symptoms, Alzheimer's disease treatment, senile dementia of the Alzheimer type, Alzheimer dementia, Alzheimer's dementia, AD, primary neuronal degeneration, senile plaques, SP, neurofibrillary tangles, NFT, cerebrocortical atrophy, central nervous system, CNS, acetylcholine, acetylcholinesterase, butyrylcholinesterase, NMDA, memantine

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Contributor Information and Disclosures

Author

Heather S Anderson, MD, Assistant Professor, Staff Neurologist, Department of Neurology, Alzheimer and Memory Center, University of Kansas Medical Center
Heather S Anderson, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Central Plains Geriatric Education Center Honoraria Speaking and teaching

Medical Editor

Joseph Quinn, MD, Assistant Professor, Department of Neurology, Portland VA Medical Center, Oregon Health Sciences University
Joseph Quinn, MD is a member of the following medical societies: American Academy of Neurology, Society for Neuroscience, and Society for Pediatric Radiology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale
Richard J Caselli, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, American Neurological Association, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Howard A Crystal, MD, Professor, Departments of Neurology and Pathology, State University of New York Downstate; Consulting Staff, Department of Neurology, University Hospital and Kings County Hospital Center
Howard A Crystal, MD is a member of the following medical societies: American Academy of Neurology and American Neurological Association
Disclosure: Medivations Honoraria Consulting

 
 
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