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Dementia: Confirming the Diagnosis

Dementia_Confirming_DiagnosisThe number of Americans with dementia from Alzheimer’s disease (AD) is expected to triple over the next 40 years. That forecast from a recent study1 is simply the latest to confirm that, as America ages, we will be faced with unprecedented numbers of patients with dementia. An estimated 5.4 million Americans have AD. By 2050, the incidence of AD is expected to reach a million people a year with a total prevalence of 11 to 16 million people. In 2010, the cost for dementia was between $157 billion to $215 billion.2

Estimates are less certain about the number of patients with other forms of dementia, but these too will grow as the elderly population increases. With the increasing recognition that early diagnosis may promote better care, it is more important than ever to get the diagnosis right. According to Stephen Salloway, MD, Professor of Neurology at Brown University in Providence, RI, and an expert on early dementia diagnosis, “The foundation of good medical practice rests on an accurate diagnosis.” The right diagnosis guides treatment decisions, indicates the likely prognosis, and helps families understand and prepare for what to expect.

Dementia_QuoteRule Out Treatable Causes

When a new patient presents with dementia, the most important step is to rule out reversible causes of memory loss. And there are many confounding disorders, including polydrug interaction, vitamin B12 deficiency, hypothyroidism, diabetes, dehydration, renal disease, and others. A screen for these and other common causes of treatable dementia can quickly uncover whether the patient’s problems may be reversible. Such a screen is recommended by the American Academy of Neurology, the American Geriatrics Association and others in the routine evaluation of a demented patient.

Screening for Secondary Causes of Dementia

Guidelines from the American Academy of Neurology3 indicate that evidence supports the following tests in the routine evaluation of the demented patient: depression screening, complete blood cell count, glucose, thyroid function tests, serum electrolytes, urea nitrogen/creatinine, vitamin B12 levels, liver function test.

“Doctors should screen for co-morbidities that we can treat,” says Joseph Higgins, MD, FAAN, Medical Director for Athena Diagnostics. “This also includes a screen for depression and a review of medication side effects, both of which can mimic dementia. We hope primary care physicians will do these screens as part of the annual wellness visit in their patients over 65 years.” “Medicare is currently recommending cognitive screening tools, but these may become mandatory for reimbursement in the future.”

For patients without such treatable causes, or who are not responding to treatment, referral to a neurologist is appropriate. Determining the cause of dementia can still present a significant challenge at this stage, as the early presentations of many types of dementia may overlap. Clinical acumen is still the most important skill, but it can be augmented by testing when the situation warrants.

And despite the still-modest symptomatic therapies available for treatment of AD, “you need the diagnosis” to use them wisely, Dr. Salloway says.

Tests Offer Assistance with Diagnosis and Prognosis

A family history of dementia may suggest a genetic cause, and support genetic testing for mutations in genes linked to Alzheimer’s disease (APP, presenilin, and APOE). Structural imaging may reveal lesions consistent with vascular dementia.

PET imaging with the radioligand florbetapir was approved by the US Food and Drug Administration in 2011 for the estimation of amyloid plaque burden in the brain in adults with cognitive impairment. A negative scan is inconsistent with a diagnosis of AD, while a positive scan is consistent with, but not definitive for AD.

Testing is also available for Aß42, tau, and phospho-tau, three cerebrospinal fluid proteins that have been linked to the rate of Alzheimer’s progression. A 2012 study of patients with mild cognitive impairment (MCI) indicated that baseline elevation of tau and phospho-tau were strongly associated with a faster rate of conversion to AD, compared to those with lower protein levels.4 “I think that’s a clue” about what to expect, Dr. Salloway says. “We not only want to know ‘yes’ or ‘no,’ but also how quickly a patient is likely to progress.” That information can help the family understand more and help them plan how best to accommodate the changes in their future.

“When you definitively diagnose a disease such as Alzheimer’s disease, you have a better understanding on what to expect, and you can advise patients on potential treatments and what they should or should not do,” Dr. Higgins says. “However, that’s true for all diagnostics, not only neurology.”

References

1. Hebert LE, Weuve J, Scherr PA, et al. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology. 2013 Feb 6. [Epub ahead of print] 2. Hurd MD, Martorell P, Delavande A, et al. Monetary Costs of Dementia in the United States. N Engl J Med. 2013; 368:1326-1334 3. “Detection, diagnosis, and management of dementia: AAN guideline summary for physicians.” aan.com/professionals/practice/pdfs/dementia_guideline.pdf. Accessed April 1, 2013. 4. Buchhave P, Minthon L, Zetterberg H, et al. Cerebrospinal fluid levels of β-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry. 2012 Jan;69(1):98-106.

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