The first symptoms of Alzheimer disease (AD) can vary from person to person, making its diagnosis difficult.

While there are challenges involved in identifying patients with cognitive impairment, it is essential to consider all possible differential diagnoses due to high rates of AD misdiagnosis and overdiagnosis. And when a patient is diagnosed with AD, working with their family on treatment and care is crucial to their well-being.

 

Early signs and symptoms

Early symptomatic AD—also sometimes categorized as mild cognitive impairment (MCI)—describes when a person has more memory problems than normal for their age, but the symptoms are not yet serious enough to interfere with their everyday life.

Other symptoms and signs linked to MCI include movement difficulties and issues with the sense of smell.

According to the National Institute on Aging, these difficulties can include:

Alzheimer's disease fact sheet. National Institute on Aging. Updated July 8, 2021.

 

• Wandering

• Getting lost while driving and other driving difficulties

• Misplacing things

• Difficulty handling money and paying bills

• Repeating questions

• Difficulties finding words during conversations

• Having trouble keeping track of dates and appointments

• Taking longer than would be expected to complete normal daily tasks

• Impaired reasoning and judgment

• Personality and behavior changes that are noticed by family members

When evaluating patients, it is also important to conduct interviews with a patient's family member (or friend or caregiver) about changes in the person’s thinking skills and abilities.

 

Screening for early AD

The Medicare Annual Wellness Visit provides a good opportunity to assess for cognitive changes in patients. A clinical algorithm for detecting AD during this visit has been developed for clinicians by the Alzheimer's Association.

Medicare annual wellness visit algorithm for assessment of cognition. Alzheimer’s Association.

GPCOG and Mini-Cog are screening tools the association has recommended to be effective for primary care and other specialties.

 

There are also additional screening tools that can be given to family members who are concerned about their loved ones. The National Institute on Aging also lists several cognitive screening tools without making a specific recommendation.

Alzheimer's and related dementia resources for professionals. National Institute on Aging. Updated November 5, 2021.

 

However, the US Preventive Services Task Force (USPSTF) has recommended that “current evidence is insufficient to assess the balance of benefits and harms of screening for cognitive impairment in older adults.”

USPSTF final recommendation statement: Cognitive impairment in older adults: Screening. U.S. Preventive Services Task Force. February 25, 2020.

The USPSTF did not find any advantages in screening with respect to quality of life, mood, or increased diagnostic rates.

 

 

Lack of formal diagnostic guidelines

The most current formal AD diagnosis guidelines are from 2011.

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.

Because of the lack of recent guidelines, clinicians may consider using the recommendations in the following three documents from highly regarded sources:

 

• Lancet Commission: Dementia prevention, intervention, and care: 2020 report of the Lancet Commission

  Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396(10248):413–446.

   

• American Academy of Neurology: Practice guideline update summary: Mild cognitive impairment

  Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary: Mild cognitive impairment. Neurology. 2018;90(3):126–135.

   

• Alzheimer’s Association: Management of AD for professionals

  Management. Alzheimer’s Association.

   

 

Differential diagnosis

Differential diagnosis of early AD is an important approach because of the many other conditions that can cause cognitive deficits and dementia.

Anderson A, Malone M. The differential diagnosis and treatment of mild cognitive impairment and alzheimer disease.J Clin Psychiatry. 2022;84(1):BG21120COM4.

They each have similar but clinically differentiating differences. While AD is the cause of 80% of all dementia cases, conditions to potentially rule out include:

Differential diagnosis. Alzheimer’s Association.

 

• Vascular dementia

• Mixed dementia

• Lewy Body dementia

• Parkinson disease

• Frontotemporal dementia

• Creutzfeldt-Jakob disease

• Normal pressure hydrocephalus

• Huntington disease

• Korsakoff syndrome

MDLinx advisor Mohammad Kassem, MD, a neurologist practicing in Ohio, said that it is important to rule out dementia mimics, particularly in the younger population.

These can include memory loss due to depression, psychosocial stressors, anxiety, structural brain abnormalities, obstructive sleep apnea, nutritional deficits, and quiet delirium secondary to medications or subclinical infections.

Dr. Kassem emphasized doing a detailed history of a patient's present illness screening, speaking to family members if possible, obtaining a detailed family history, and completing a thorough, careful physical examination.

According to research published by Life, potential diagnostic procedures to consider that will help identify the appropriate diagnosis include:

Cacabelos R, Naidoo V, Martínez-Iglesias O, et al. Personalized management and treatment of Alzheimer’s disease. Life (Basel). 2022;12(3):460.

 

• General clinical assessment

• Blood analyses

• Neuropsychological assessment with psychometric tools

• Cardiovascular evaluation with ECG

 

Biomarkers and genetic testing

Biomarkers are being researched with the goal of detecting early changes in the brain of people with MCI, but these are not commonly used in clinical practice yet. The intention is that they can also be used to test cognitively normal people who may be at risk for AD or MCI.

There are also genetic tests for AD, but as so many other factors can cause the disease, these are not generally recommended in clinical practice.

One of the main reasons is that genetic tests are most useful when the patient is younger, aged 30 to 60, according to the National Institute on Aging. The tests are not typically as useful in patients over age 65.

 

Referrals to specialists

If clinicians are not able to conduct an early AD evaluation on patients with MCI, they should consider referring them to a specialist such as a neurologist, neuropsychologist, or geriatrician.

Scenarios in which this may be recommended include an inconclusive diagnosis, behavioral symptoms, a patient under age 65, to get a second opinion, and to assist with family questions.