Evidence-Based Reviews

New Alzheimer’s disease guidelines: Implications for clinicians

Current Psychiatry. 2012 March;11(3):15-22

References

1. Jack CR Jr, Albert MS, Knopman DS, et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):257-262.

2. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280-292.

3. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270-279.

4. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263-269.

5. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939-944.

6. Diagnostic and statistical manual of mental disorders, 4th ed, text rev. Washington DC: American Psychiatric Association; 2000.

7. Ihl R, Frölich L, Winblad B, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of Alzheimer’s disease and other dementias. World J Biol Psychiatry. 2011;12(1):2-32.

8. Chertkow H, Massoud F, Nasreddine Z, et al. Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia. CMAJ. 2008;178(10):1273-1285.

9. McKhann GM. Changing concepts of Alzheimer disease. JAMA. 2011;305(23):2458-2459.

10. Galasko D. Biomarkers in non-Alzheimer’s dementias. Clinical Neuroscience Research. 2004;3(6):375-381.

11. Desai AK, Grossberg GT, Chibnall JT. Healthy brain aging: a road map. Clin Geriatr Med. 2010;26(1):1-16.

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15. Mittelman MS, Haley WE, Clay OJ, et al. Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease. Neurology. 2006;67(9):1592-1599.

Table 2

5 biomarkers incorporated into the 2011 AD criteria

Category	Biomarkers
Biomarkers of Aβ accumulation	Abnormal tracer retention on amyloid PET imaging
Biomarkers of Aβ accumulation	Low CSF Aβ42
Biomarkers of neuronal degeneration or injury	Elevated CSF tau (total and phosphorylated tau)
	Decreased fluorodeoxyglucose uptake on PET
	Atrophy on structural magnetic resonance imaging
Aβ: beta-amyloid; AD: Alzheimer’s disease; CSF: cerebrospinal fluid; PET: positron emission tomography Source: References 1-4

Box

The new AD criteria: Risks and benefits of earlier diagnosis

The earlier an Alzheimer’s disease (AD) diagnosis is made, the less certain it is AD.^a Biomarkers typically found in individuals with AD also can be found in patients with dementia not caused by AD, such as vascular dementia, as well as in individuals who may never develop dementia.^b Additionally, there is no certainty that a patient in an early phase of AD will develop clinical dementia. Falsely diagnosing a patient with AD may lead the individual and their family to feel helpless, hopeless, depressed, anxious, or ashamed and to spend money and other resources preparing for a prognosis that may never come to fruition. Clinicians may feel compelled to assess for biomarkers using expensive, invasive tests that are not yet standardized in an attempt to support the AD diagnosis.

Early diagnosis of AD has many benefits that should not be overlooked, however. It provides patients and their families an opportunity to become familiar with the disease course, which may help some patients cope with the diagnosis. Patients diagnosed in the early stages would be able to make important decisions regarding health care, social, and financial planning before they develop pathology that limits their executive planning abilities or become functionally impaired.

Diagnosing an illness when there are no disease-modifying therapies available is not futile. Some patients with newly diagnosed AD in the pre-dementia phases may want to participate in clinical research trials to help develop therapies for AD. Some data suggest that AD treatment appears to provide the greatest benefit when initiated early in the disease course and maintained over a long duration.^c Eventually, we may be able to tailor specific AD treatments in different phases of the disease. For instance, we may discover treatments for patients who show evidence of beta-amyloid plaques but not neuronal injury, or vice versa. Patients also may benefit from education on nonpharmacologic treatments, including reducing vascular risk factors to help improve brain aging,^d reducing stress, and learning cognitive strategies such as using mnemonics to aid memory.

In many clinical settings, patients are being clinically diagnosed with mild cognitive impairment (MCI). Research indicates that patients with MCI are at near-term risk of developing dementia, particularly dementia of the Alzheimer’s type.^d,^e Presently, no definite transition points demarcate MCI from dementia; this progression is based upon clinical judgment.

In the last decade, researchers have begun to describe a syndrome of subjective cognitive impairment (SCI), which may be a phase that precedes the MCI phase of AD.^f Patients with SCI report cognitive deficits (eg, forgetfulness and word-finding difficulties) but have no objective evidence of cognitive impairment on neuropsychological tests. Cognitive problems associated with SCI do not cause functional decline.^g SCI may reflect the minimal cognitive complaints mentioned in the research criteria for the preclinical phase of AD. Eventually, biomarkers may be able to help clinicians more accurately predict which patients with SCI are most likely to progress to the MCI or dementia phase of AD.

References

Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270-279.
Galasko D. Biomarkers in non-Alzheimer dementias. Clinical Neuroscience Research. 2004;3(6):375-381.
Geldmacher DS. Treatment guidelines for Alzheimer’s disease: redefining perceptions in primary care. Prim Care Companion J Clin Psychiatry. 2007;9(2):113-121.
Chertkow H, Massoud F, Nasreddine Z, et al. Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia. CMAJ. 2008;178(10):1273-1285.
Rosenberg PB, Lyketsos C. Mild cognitive impairment: searching for the prodrome of Alzheimer’s disease. World Psychiatry. 2008;7(2):72-78.
Reisberg B, Shulman MB, Torossian C, et al. Outcome over seven years of healthy adults with and without subjective cognitive impairment. Alzheimers Dement. 2010;6(1):11-24.
Desai AK, Schwarz L. Subjective cognitive impairment: when to be concerned about ‘senior moments.’ Current Psychiatry. 2011;10(4):31-44.

Clinical applications

Although pharmacologic therapies for the early phases of AD are not yet available, research supports implementing nonpharmacologic modalities in older adults with MCI as well as those without any cognitive impairment (Table 3).^8,11 Growing evidence suggests physicians should encourage patients to lead an active and socially integrated lifestyle that includes leisure activities, cognitive stimulation, meditation, a balanced diet, and daily exercise.⁸ Practitioners should treat vascular risk factors in geriatric patients with and without cognitive impairment to optimize healthy brain aging and reduce the risk of cardiovascular disease and stroke.¹¹ By raising awareness of available treatments for early phases of AD, we may be able to reduce the anxiety and sense of helplessness or hopelessness that may accompany an AD diagnosis.