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Expert Answers to Your Questions on Brain Health: Practical Tips for Nonspecialists

Physician Assistants/Physician Associates: 0.25 AAPA Category 1 CME credit

Nurse Practitioners/Nurses: 0.25 Nursing contact hour

Physicians: maximum of 0.25 AMA PRA Category 1 Credit™

ABIM MOC: maximum of 0.25 Medical Knowledge MOC point

Released: April 03, 2025

Expiration: April 02, 2026

Anton P. Porsteinsson
Anton P. Porsteinsson, MD
CME/CE Information

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As the population ages and the prevalence of Alzheimer’s disease (AD) increases, preservation of cognitive function becomes crucial to patients across virtually all clinical practice settings. In this commentary, Anton P. Porsteinsson, MD, answers audience questions from a recent Think Tank Webinar entitled, “Brain Health Champions: Prevention of Cognitive Decline Through Patient Engagement and Risk Management”.

What workup and diagnostic steps would you recommend for a primary care provider (PCP) before referral to a dementia specialist? What determines whether a patient needs specialist care or can be managed in primary care?

PCP Checklist:

  • Confirm medical and family history
  • Review the patient’s medications for any that could cause cognitive impairment
  • Perform blood tests to eliminate potential reversible causes of cognitive impairment
  • Conduct a quick clinical assessment to confirm the presence of cognitive impairment

Before referring a patient to a dementia specialist, a PCP should perform an initial evaluation to assess the patient’s symptoms, rule out other conditions, and gather relevant information. This includes:

History

  • Patient History: Ask about the onset, progression, and nature of cognitive symptoms including memory loss, disorientation, difficulty with language, changes in executive function, and behavior
  • Medical History: Inquire about past medical conditions, medications (including over-the-counter), and family history of dementia or neurodegenerative diseases
  • Functional History: Assess the impact of cognitive symptoms on daily activities (eg, driving, managing finances, personal care)
  • Psychiatric History: Explore mood disturbances such as depression, anxiety, or prior psychiatric conditions, which can sometimes mimic or coexist with dementia

Physical and Brief Neurologic Examination

  • General Exam: Evaluate vital signs, weight, and signs of systemic illness (eg, thyroid disease, infections)
  • Neurologic Exam: Check reflexes, muscle strength, coordination, and signs of focal neurologic deficits (eg, gait disturbances, visual problems)

Brief Cognitive Testing

  • Mini-Mental State Examination (MMSE), Mini-Cog, or Montreal Cognitive Assessment (MoCA) for general cognitive impairment

Screening for Reversible Causes

  • Bloodwork to rule out reversible causes of cognitive decline such as:
    • Thyroid function tests (eg, TSH, free T4)
    • Vitamin B12
    • Complete blood count
    • Comprehensive metabolic panel
    • Syphilis testing and HIV if there is suspicion of a neurologic infection or disease
  • Urinalysis: To check for urinary tract infection, especially in elderly patients who may have altered mental status
  • Medication review: Check for medications that may affect cognition to weigh risks and benefits and ensure optimization/minimum effective doses

Imaging Studies

  • Head MRI or CT if MRI is unavailable/contraindicated

Referral to a Specialist

  • If the workup suggests atypical or complicated dementia (for example with troublesome behavioral symptoms) that requires specialized evaluation or treatment, referral to a neurologist, geriatrician, or geriatric psychiatrist may be appropriate.

By performing these diagnostic steps, the PCP can help clarify whether the patient has a cognitive disorder, provide information to guide the referral to a dementia specialist, and potentially delay the progression of symptoms with early interventions.

Can you provide more details on cognitive assessment tools available for nonspecialist use? Which are free to use, which require training certification, which can be easily fit into clinical visits?
Cognitive assessment is an essential step in diagnosing cognitive decline or dementia. Nonspecialists, like PCPs, can use several tools to assess cognition in their patients. These tools vary in terms of complexity, training requirements, time needed, and whether they are freely available or not. Here is a breakdown of common cognitive assessment tools that are useful for nonspecialists.

Mini-Mental State Examination (MMSE)

  • Description: The MMSE is one of the most widely used cognitive screening tools, assessing multiple cognitive domains such as orientation, attention, memory, language, and visuospatial skills.
  • Cost: The MMSE requires a license for use, though some versions are publicly available.
  • Certification/Training: Formal training is not required, but understanding the scoring and interpretation is important for accurate results.
  • Time to Administer: The MMSE takes approximately 10 minutes to complete.
  • Ease of Use: The MMSE can be easily incorporated into a standard clinical visit. It is brief and straightforward but may be challenging to score for some without familiarity.
  • Notes: The MMSE has been criticized for not being sensitive to mild cognitive impairment (MCI) and for cultural bias. It also has a "ceiling effect," meaning it might not be sensitive in individuals with higher education levels.

Montreal Cognitive Assessment (MoCA)

  • Description: The MoCA is a more comprehensive cognitive screening tool than the MMSE and is designed to detect MCI earlier. It assesses memory, attention, executive function, language, visuospatial skills, and orientation.
  • Cost: The MoCA is freely available for clinical use.
  • Certification/Training: No formal certification is required, but there is an online training module available (recommended to understand the tool better and improve administration accuracy).
  • Time to Administer: The MoCA takes approximately 10 to 15 minutes to complete.
  • Ease of Use: The MoCA is a popular choice for clinical settings and can be administered in a short time. It is more sensitive to early cognitive decline than the MMSE.
  • Notes: The MoCA is available in several versions and multiple languages and includes a scoring sheet. It is a better option for detecting early cognitive changes, especially in people with higher education.

Mini-Cog

  • Description: The Mini-Cog is a very brief cognitive screening tool, combining a 3-word recall and a clock-drawing test to assess memory and executive function.
  • Cost: The Mini-Cog is free to use and publicly available.
  • Certification/Training: No formal certification is required. However, understanding the scoring is necessary for accurate interpretation.
  • Time to Administer: The Mini-Cog takes approximately 3 to 5 minutes to complete.
  • Ease of Use: The Mini-Cog is very easy to administer and can be done during a routine visit. It is ideal for quick screening.
  • Notes: The Mini-Cog is an excellent option when time is limited. Its sensitivity is lower than that of more comprehensive tools like the MoCA, but it remains useful for initial screening.

Clock Drawing Test (CDT)

  • Description: The CDT is a quick test of visuospatial and executive function. The patient is asked to draw a clock showing a specific time (eg, 11:10).
  • Cost: The CDT is free to use.
  • Certification/Training: No formal training is required, but interpretation can vary depending on the criteria used.
  • Time to Administer: The CDT takes approximately 2 to 5 minutes to complete.
  • Ease of Use: The CDT is very brief and can easily fit into a routine clinical visit.
  • Notes: The CDT is often used as part of other cognitive assessments (eg, MoCA) or by itself for a quick cognitive screen.

Saint Louis University Mental Status (SLUMS) Exam

  • Description: The SLUMS exam is a screening tool designed to assess cognitive function in older adults, with a focus on detecting MCI and dementia. It evaluates several domains, including attention, memory, executive function, and orientation. It is particularly helpful for distinguishing between normal aging, MCI, and dementia.
  • Cost: The SLUMS exam is free for clinical use.
  • Certification/Training: No formal certification is required, but some understanding of how to score and interpret the results is important for accuracy.
  • Time to Administer: The SLUMS takes approximately 7 to 10 minutes to complete.
  • Ease of Use: The SLUMS exam is brief and can be easily administered during a clinical visit. Its administration is relatively quick, and it can help distinguish between normal aging and cognitive impairment.
  • Notes: SLUMS is available in both English and Spanish and has been shown to be sensitive for detecting early cognitive changes. It is particularly useful in identifying individuals with MCI and has different cutoff scores depending on education level, which can make it more accurate for diverse populations.

What is the current status of blood-based tests for biomarkers of AD pathology? Do you expect these will soon be available for clinical use in place of CSF testing?

Biomarkers support the diagnosis of AD by reflecting the underlying pathology such as the presence of Aβ and aggregated tau within the brain. They should be used by healthcare professionals (HCPs) as part of the multistage diagnostic process and not in isolation. For instance, if they are approved by the FDA, blood-based biomarkers could be used to identify patients at risk of developing AD and for monitoring disease progression, which would also reduce the current capacity constraints associated with CSF testing and PET imaging.

At present, only a limited number of approved blood-based assays are available to HCPs to detect AD pathology and none are yet FDA approved. Blood-based tests for AD biomarkers are advancing rapidly, with promising markers showing high potential for clinical application. Although these tests are not yet ready to completely replace CSF testing or amyloid PET scans, they are likely to become a valuable tool for early AD detection, screening, and monitoring. P-tau217 is a promising biomarker for detecting preclinical and clinical forms of AD.

Given that blood testing is already a well-established part of clinical routines globally and can easily be performed in a variety of clinical settings, blood-based biomarkers could eventually serve as the potential first step of a multistage diagnostic process. As the assay technology improves and additional validation studies are completed, blood-based tests may offer first level of screening and potentially replace certain CSF tests and amyloid PET scans in the future, especially in clinical settings where noninvasive and cost-effective options are needed. However, it is expected that CSF testing and PET scans will remain essential in cases where further confirmation is required.

Is there any relevance of apolipoprotein E (apoE) status at the MCI or early dementia stage? Is it relevant for MCI or dementia of non-Alzheimer’s types? When do you recommend apoE testing?
ApoE testing is used to assess genetic risk for AD, particularly for the apoE ε4 allele, which has been associated with an increased risk of developing AD. Although not routinely used in clinical practice, HCPs may request apoE genotyping, as this can help assess the genetic risk of developing AD. ApoE is the dominant cholesterol carrier within the brain that supports lipid transport and injury repair, and the apoE gene exists as 3 polymorphic alleles: apoE ε2, ε3, and ε4. The ε4 allele of apoE is associated with increased AD risk, whereas the ε2 allele is protective. The number of apoE ε4 alleles a person carries increases their risk of developing AD and the age of disease onset. Homozygous ε4 carriers (those with 2 copies of the ε4 allele) have the greatest risk of developing AD and the earliest average age of onset.

ApoE testing is most frequently used when the dementia diagnosis is uncertain and genetic risk is relevant such as if there is a strong family history of AD, especially if it appears to follow an earlier onset pattern. Furthermore, apoE ε4 allele carriers are at higher risk for progressing from MCI to AD, so understanding whether a patient carries this allele can help inform decisions about monitoring, treatment options, and lifestyle interventions. ApoE testing can provide valuable insights into an individual's genetic risk for AD, but its role in clinical practice is limited and should be approached carefully. It is most useful when combined with other diagnostic tools, such as clinical evaluation, imaging, and other biomarkers. Pre- and posttest counseling is essential to help individuals understand the implications of the test results, and the test should be used thoughtfully, rather than as a routine part of Alzheimer's diagnosis or screening.

More recently, apoE testing can play an important role in determining eligibility and treatment considerations for emerging AD therapies, particularly lecanemab and donanemab. ApoE ε4 carriers are at increased risk of certain side effects related to antiamyloid therapies, such as ARIA (amyloid-related imaging abnormalities), which can cause brain swelling or microhemorrhages. Knowing whether patients carry the apoE ε4 allele can help HCPs guide treatment decisions and assess both the potential benefits and the risks of starting treatment.

In some practice settings, apoE genotyping can only be conducted by a genetic counselor; a referral for more comprehensive genetic testing may be considered by the HCP if there is a family history of early-onset AD or dementia. Consumer tests are also becoming more readily available for patients wanting to determine their risk of developing diseases such as AD based on genetic risk factors.

Do you recommend any dietary supplements for patients with MCI or early AD? If so, what is the scientific evidence?
When it comes to MCI or early AD, there is a growing interest in the potential role of dietary supplements to support brain health, slow cognitive decline, or even prevent progression to Alzheimer's. However, the scientific evidence supporting the use of dietary supplements for these conditions is mixed, and no supplement has been definitively proven to halt or reverse AD. In all cases, dietary supplements should complement a holistic approach to brain health—which includes a balanced diet, physical exercise, mental stimulation, and management of cardiovascular health—rather than being used as primary interventions. Always consult with an HCP before starting any new supplement, especially in the context of cognitive decline or AD. That said, some supplements have shown promise in supporting cognitive function, often in combination with a healthy lifestyle. These include:

  • Omega-3 fatty acids (DHA and EPA): May help support brain health, but evidence is mixed
  • B vitamins (B6, B12, and folate): Can be considered in individuals with elevated homocysteine or vitamin deficiencies but the evidence for their effectiveness in AD is inconclusive
  • Vitamin D: Recommended for individuals who are deficient in vitamin D but its effectiveness in treating MCI or AD remains uncertain
  • Ginkgo biloba: May offer mild benefits for cognitive function but the evidence is inconsistent and should be used with caution as it has many potential interactions with medications
  • Curcumin: Potential anti-inflammatory benefits but insufficient evidence for its effectiveness in AD or MCI
  • Caffeine: Moderate consumption may have cognitive benefits but it should be used cautiously, especially in those with sleep disturbances or other health issues

For more in-depth education on integration of brain health concerns into your practice, visit our Brain Health Champions program page for a downloadable slideset and in-depth commentaries specific to primary care, ob/gyn, psychiatry, and general neurology.

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