Diagnosing Alzheimer's Disease in Primary Care: 5 Things to Know

Larry Culpepper, MD, MPH


July 18, 2023

Alzheimer's disease (AD) is a neurogenerative disorder marked by cognitive and behavioral impairment. It is the most common cause of dementia. In 2017, 6.08 million people in the United States had either clinical AD or mild cognitive impairment due to AD. That number is expected to increase to about 15 million by 2060. Although the cause of this disorder is unknown, investigators believe that multiple environmental and genetic risk factors affect the development of AD and dementia. As a result of its prevalence, primary care providers play a critical role in diagnosing and managing this disease.

Here are five things to know about diagnosing and managing AD in primary care.

1. Patients with AD should be tested for comorbid conditions.

Although AD is the most common cause of dementia, comorbidity with other causes exists in over 50% of people with this condition. Rates of comorbidity increase with age, and this presents challenges in diagnosis for primary care providers. Comorbidity may affect presenting symptoms and behaviors, impairments, and the support required of caregivers, as well as evolution of these over time.

Those with AD alone frequently present with episodic memory concerns (eg, recalling specific events or learning new information) accompanied by apathy or depression. In contrast, those with vascular dementia often present early with intact memory but executive function impairment such as difficulty making decisions. Additionally, these individuals may have motor dysfunction such as slowed gait and balance problems. The impact of vascular dementia differs on the basis of the vascular pathology involved and brain areas affected. Those with Lewy body dementia  may present with sleep disturbances, visual hallucinations, and visuospatial impairment. Individuals with frontotemporal lobar degeneration, which often presents in people in their 40s and 50s, retain their memory during early disease while exhibiting marked personality and behavior changes and language difficulties. Parkinson's disease usually presents with slowness, rigidity, tremor, gait and balance problems, and cognitive symptoms.

In autopsy studies, pure AD accounts for about half of dementia cases, while vascular dementia and AD is present in about one fourth. Those with AD and Lewy body dementia and other combinations account for the remainder. There are no widely accepted criteria for a diagnosis of mixed dementia. Characterizing the symptoms, behaviors, and functional impairments that a specific patient is experiencing remains the foundation of treatment strategies, recognizing that more than one pathologic process may be involved.

2. Cognitive impairment evaluations should be performed to determine where the patient is in the AD disease course.

AD is a continuum that progresses through three phases: preclinical AD (no symptoms), mild cognitive impairment due to AD (mild symptoms that do not interfere with everyday activities), and dementia, with this stage divided into mild (symptoms interfere with some everyday activities), moderate (symptoms interfere with many everyday activities), and severe (symptoms interfere with most everyday activities). The length of each phase is influenced by age, genetics, sex, education, and modifiable lifestyle factors. Of note, diagnosis of mild cognitive impairment requires evidence of intraindividual change. Early detection of mild cognitive impairment and AD allows patients to prepare for end-of-life decisions (eg, advance directives, living wills, power-of-attorney designations, finances) and engage in lifestyle changes that might delay disease progression.

The Medicare annual wellness visit includes a required cognitive evaluation, although it does not specify a process. An effective, efficient approach is for staff to use a brief, validated, partner-focused screening tool for all patients prior to their wellness visits. A tool well suited for primary care practice is the Ascertain Dementia 8 (AD8) informant-based questionnaire. The AD8 queries about changes in memory, orientation, executive function, and interest in activities. Completion takes about 3 minutes, can be administered by phone, and is easy to score. While completion by an informant is preferred, these may be used as patient self-administered screens. If an informant affirms two or more of the eight AD8 questions, cognitive impairment is likely. Longer informant questionnaires are available. When the AD8 raises concern, primary care clinician–administered tools such as the Mini-Cog can extend understanding of the patient's cognitive status, either for monitoring at the subsequent yearly wellness visit or to initiate further assessment at the current visit. The Mini-Cog is one of several suitable tools in primary care; selection is based on clinician preference, takes about 3 minutes to complete, and includes a three-word delayed-recall assessment and a clock-drawing test. Using a tool-based approach such as this improves primary care identification of patients with mild cognitive impairment or dementia compared with spontaneous detection (83% vs 59%, respectively).

3. Reversible causes should be considered when patients show symptoms of mild cognitive impairment.

In addition to the potential causes of dementia previously discussed (eg, AD, vascular dementia, Lewy body dementia), when mild cognitive impairment is suspected, further evaluation should be done to identify possible reversible causes, including medication side effects. Reversible causes can be detected in patient history, physical examinations, laboratory and imaging tests, and hearing and vision exams. Clinicians should assess for metabolic disorders (eg, B12 deficiency or thyroid disease), infectious diseases (eg, HIV or syphilis), sleep disorders (eg, obstructive sleep apnea), brain tumors or paraneoplastic syndromes, and psychiatric disorders.

Symptoms of cognitive impairment as a result of depression are seen in older adults. Moreover, signs of depression often overlap with depressive symptoms in dementia, including altered sleep, difficulty concentrating, and decreased energy. This should be considered when making a diagnosis.

4. Use Biomarkers to Assess Cognitive Impairment

Biomarkers may be helpful in assessing patients at high risk of developing cognitive impairments and in predicting the eventual development of AD from amyloid overproduction, detecting those with early cognitive changes, and possibly in predicting the rate of progression once AD has been diagnosed. Specialty medical facilities are beginning to gain experience with several of these biomarker tests. In the future, biomarkers may provide early prognosis for those who would benefit from specific treatment.

The Alzheimer's Association notes, however, that relevant appropriate-use criteria have not been developed for use in primary care. No large, prospective studies have been done in primary care where the prevalence of neurodegenerative diseases is lower than in specialized memory settings. Patients with cognitive symptoms in primary care are much more diverse with more frequent comorbidities, copathologies, and more diverse socioeconomic backgrounds, all of which are likely to affect their interpretation and validity.

Accumulation of beta-amyloid may occur for many years preceding clinical AD. The ratio in cerebrospinal fluid (CSF) of Aβ42/Aβ40 is a robust biomarker for beta-amyloid pathology. A low ratio accompanies selective CSF depletion of Aβ42 as it is deposited in beta-amyloid plaques as pathology develops. While the Aβ42/Aβ40 ratio change indicative of pathology in CSF is 40%-60%, in plasma this is reflected in only an 8%-15% reduction. Tau biomarkers reflect damage owing to the development of tau tangles, heralding the onset of cognitive decline. Plasma p-tau biomarkers are more robust than amyloid biomarkers. For instance, plasma p-tau levels are increased 250%-600% in AD dementia. In memory clinic settings, this marker can separate AD dementia from other neurodegenerative diseases with high diagnostic accuracy. Other beta-amyloid– and tau-based biomarkers for non-AD neurodegenerative disorders, including Lewy body dementia and Parkinson's disease, are also in development. Further research is necessary before these markers can be introduced in clinical practice.

5. Additional evaluations are necessary to determine an appropriate treatment regimen.

Developing an effective treatment plan may require assessments to identify a patient's affected cognitive domain(s), the severity of impairment, and the availability of family caregivers. Evidence of interference with independence in everyday activities is required for the diagnosis of AD dementia. In primary care, the Instrumental Activities of Daily Living (IADL) scale, also known as the Lawton-Brody scale, and the Functional Activities Questionnaire (FAQ) are practical tools for monitoring functional changes and take approximately 10-15 minutes to administer. The IADL scale assesses seven of the more complex activities required for independent functioning (shopping, housekeeping, using the telephone, preparing meals, using transportation, taking medications, and managing finances). The FAQ assesses 10 activities of daily living (shopping, handling finances, preparing a meal, traveling, remembering appointments; and paying attention to, understanding, and discussing television, books, or magazines). Referral for neuropsychiatric testing may be considered to define affected cognitive domains (learning and memory, language, executive function, complex attention, perceptual motor [visuospatial], social cognition). Such evaluations can help with planning for and monitoring disease progression.

Over 80% of patients with AD exhibit behaviors problematic for them and for caregivers. The Neuropsychiatric Inventory Questionnaire (NPIQ), completed by patient caregivers, is meant to capture behavioral changes in individuals with AD and may be helpful in planning management. The NPIQ includes questions about 12 neuropsychiatric symptoms and requires 5 minutes. Evaluating caregivers' physical and emotional health and support systems can also foster collaboration to optimize care.

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