The Differential Diagnosis and Treatment of Mild Cognitive Impairment and Alzheimer Disease

J Clin Psychiatry 2023;84(1):BG21120COM4
To cite: Anderson A, Malone M. The differential diagnosis and treatment of mild cognitive impairment and Alzheimer disease. J Clin Psychiatry. 2023;84(1):BG21120COM4
a https://doi.org/10.4088/JCP.BG21120COM4
© Copyright 2022 Physicians Postgraduate Press, Inc.

^aBanner Alzheimer’s Institute, Tucson, Arizona

The substantial clinical heterogeneity seen among patients with Alzheimer disease (AD) makes the associated differential diagnosis difficult, even for experienced clinicians. In addition to memory and learning impairment, an AD diagnosis requires demonstrated impairment in another cognitive domain, namely complex attention, executive function, language, perceptual-motor, and/or social cognition.¹ Of these deficits, cognitive decline has the largest impact on day-to-day living.

It is essential that clinicians exclude alternative causes for changes in cognitive functioning, as the correct treatment plan for an individual depends on the underlying condition. Psychiatric disorders, such as depression and schizophrenia, can resemble dementia and can cause executive dysfunction or thought disorders. Medical issues such as thyroid disease and vitamin deficiencies can similarly mimic AD. Findings from comprehensive patient assessments and laboratory work can assist with the differential diagnosis.

Frontotemporal dementia, Parkinson disease, primary progressive aphasia, vascular dementia, dementia with Lewy bodies, and other dementias often present similarly to AD.

Relative to AD, frontotemporal dementia usually has a younger age at onset and causes personality changes and impulsive behaviors. Parkinsonian features, namely tremor and rigidity, accompany Parkinson disease, whereas a patient experiencing early language difficulties may be experiencing fluent or non-fluent primary progressive aphasia. Patients with a risk of vascular disease, a history of cerebrovascular disease, or vascular lesions present on a magnetic resonance imaging scan could have vascular dementia. Early visual hallucinations, fluctuating attention, REM behavioral sleep disorder, and/or Parkinsonism are all highly suggestive of dementia with Lewy bodies.²

Cholinesterase inhibitors, memantine, and other historical treatments for AD target symptoms of the disease, rather than the condition’s underlying causes.³ However, there is much excitement surrounding recent advances and research regarding efforts to target the pathology of the disease. After data from a pair of double-blind, randomized, and placebo-controlled trials, EMERGE and ENGAGE, showed reduction in amyloid burden in the brain in patients with stage 3 AD, or mild cognitive impairment (MCI), and patients with stage 4, or mild Alzheimer dementia, aducanumab became the first disease-modifying therapy to be approved by the US Food and Drug Administration.⁴ Amyloid-related imaging abnormalities (ARIA), edema (-E) and/or hemosiderin (-H), were detected in 41% of patients^4,5 treated with aducanumab versus 10% placebo. Clinicians should be aware of and watch for ARIA symptoms when treating patients with aducanumab.

Researchers are now looking toward preventative treatments for AD capable of interrupting the biological cascades that lead to dementia. In the future, testing for biomarkers could play an outsized role in preventative treatment and may help clinicians stratify patients by risk and identify the most appropriate targeted therapy.

Individuals often want to know measures they can take in the present to prevent or delay the onset of dementia. According to dementia expert James Ellison, MD, MPH, to address this common question, clinicians can use the acronym DANCERS to provide their patients with helpful preventative tips.⁶ DANCERS stands for disease management, activity, nutrition, cognitive training, engaging with others, relaxation, and sleep. Disease management of diabetes, hypertension, hyperlipidemia, and obesity can help reduce risk. Activity, particularly aerobic exercise, benefits the brain as well as the heart. Nutrition, such as the MIND diet (a combination of Mediterranean and DASH diets), can lower the likelihood of dementia. Cognitive training, such as crossword puzzles or Sudoku, and engaging in new activities are helpful. Activities that “stress” the brain may be more beneficial, such as learning to play a new instrument or learning a new language. Engaging with others also benefits the brain. Relaxation through activities such as meditation, yoga, and deep breathing, additionally plays an important role in promoting brain health. And lastly, adequate sleep is important as deep sleep helps to clear out amyloid in the brain.^6,7

Finally, clinicians should not forget about the second patient commonly in the room—the caregiver. Checking in with caregivers and asking them questions is an important part of a multifaceted treatment approach. Caregivers experience loss during the Alzheimer trajectory, including the loss of a relationship, a partner, a way of life, and even a career.⁸

As advances continue in the field of AD, identifying patients at risk for developing MCI and AD is becoming more possible. Improvements in AD diagnoses will help clinicians initiate treatment earlier in the disease trajectory and thereby optimize patient outcomes. Earlier intervention can lead to individuals living in their own home longer, being with their families, and maintaining their independence to greatest extent possible.

Published online: December 26, 2022.

Unlabeled and investigational usage: The faculty of this educational activity may include discussions of products or devices that are not currently labeled for use by the FDA. Faculty members have been advised to disclose to the audience any reference to an unlabeled or investigational use. No endorsement of unapproved products or uses is made or implied by coverage of these products or uses. Please refer to the official prescribing information for each product for discussion of approved indicators, contraindications and warnings.

CME Background Information

Articles are selected for credit designation based on an assessment of the educational needs of CME participants, with the purpose of providing readers with a curriculum of CME articles on a variety of topics throughout each volume. Activities are planned using a process that links identified needs with desired results.

To obtain credit, read the article, correctly answer the questions in the Posttest, and complete the Evaluation.

This Commentary section of The Journal of Clinical Psychiatry presents the highlights of the teleconference series “Screening, Diagnosing, and Treating Mild Cognitive Impairment and Mild Alzheimer Disease,” which was held on February 25, 2022. This report was prepared and independently developed by the CME Institute of Physicians Postgraduate Press, Inc., and was supported by an educational grant from Biogen MA Inc.

The teleconference was chaired by Dr Allan Anderson, MD, MMM, CMD, DLFAPA, Banner Alzheimer’s Institute, Tucson, Arizona. The faculty was Dr Matthew Malone, DO, MBA, Banner Alzheimer’s Institute, Tucson, Arizona.

CME Objective

After completing this educational activity, you should be able to:

• Diagnose patients with mild cognitive impairment or mild Alzheimer dementia
• Facilitate prompt treatment initiation for patients with mild cognitive impairment or mild Alzheimer dementia

Accreditation Statement

The CME Institute of Physicians Postgraduate Press, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Release, Review, and Expiration Dates

This Neuroscience Commentary activity was published in December 2022 and is eligible for AMA PRA Category 1 Credit through December 31, 2023. The latest review of this material was September 2022.

Financial Disclosure

The CME Institute adheres to the Standards for Integrity and Independence in Accredited Continuing Education of the Accreditation Council for Continuing Medical Education (ACCME). Any individuals in a position to control the content of a continuing education activity, including faculty, content developers, reviewers, staff, and others, are required to disclose to learners the presence or absence of any relevant financial relationships with an ACCME-defined ineligible company within the preceding 24 months of the activity. The ACCME defines an “ineligible company” as one whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

The CME Institute has mitigated all relevant conflicts of interest prior to the commencement of the activity. None of the individuals involved in the content have relevant financial relationships with ineligible companies except the following:

Marlene P. Freeman, MD, Editor in Chief, Boston, Massachusetts, has received research funding from JayMac and Sage; has been a member of the Independent Data Safety and Monitoring Committee for Janssen (Johnson & Johnson), Novartis, and Neurocrine; and has served on advisory boards for Eliem and Sage. As an employee of Massachusetts General Hospital (MGH), Dr Freeman works with the MGH National Pregnancy Registry, which receives funding from Alkermes, Aurobindo, AuroMedics, Johnson & Johnson/Janssen, Otsuka, Sage, Sunovion, Supernus, and Teva, and works with the MGH Clinical Trials Network and Institute, which receives research funding from multiple pharmaceutical companies and the National Institute of Mental Health. Dr Freeman has also received royalties through MGH for the Massachusetts General Hospital Female Reproductive Lifecycle and Hormones Questionnaire.

None of the other planners, reviewers, and CME Institute staff for this educational activity have relevant financial relationships with ineligible companies to disclose. All relevant financial relationships have been mitigated. Dr Anderson’s and Dr Malone’s financial disclosure appears on the next page.

Credit Designation

The CME Institute of Physicians Postgraduate Press, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Note: The American Nurses Credentialing Center (ANCC) and the American Academy of Physician Assistants (AAPA) accept certificates of participation for educational activities certified for AMA PRA Category 1 Credit from organizations accredited by the ACCME.

Financial Disclosure

Dr Anderson has served on the speakers/advisory boards for Biogen. Dr Malone has no financial disclosures.

Review Process

The author agreed to provide a balanced and evidence-based presentation and discussed the topic and CME objective during the planning sessions. The author’s submitted content was validated by CME Institute staff, and the activity was evaluated for accuracy, use of evidence, and fair balance by a peer reviewer who is without conflict of interest.

The opinions expressed herein are those of the faculty and do not necessarily reflect the opinions of the CME provider and publisher or Biogen MA Inc.

REFERENCES

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2. Dementia with Lewy Bodies. Alzheimer’s Disease and Dementia. https://alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/dementia-with-lewy-bodies. Accessed October 10, 2022.

3. Alzheimer’s Disease Facts and Figures. Alzheimer’s Disease and Dementia. https://www.alz.org/alzheimers-dementia/facts-figures. Accessed August 15, 2022.

4. Cummings J, Aisen P, Lemere C, et al. Aducanumab produced a clinically meaningful benefit in association with amyloid lowering. Alzheimers Res Ther. 2021;13(1):98. PubMed CrossRef

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6. An Education Tool for Mild Cognitive Impairment and Dementia. Neuro Speech Solutions. https://www.neurospeechsolutions.com/blog/dancers-cognitive-decline-prevention-education. Accessed October 11, 2022.

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8. Fazio S, Pace D, Maslow K, et al. Alzheimer’s Association dementia care practice recommendations. Gerontologist. 2018;58(suppl 1):S1–S9. PubMed CrossRef