A medical history can be obtained through a clinical interview with the person with cognitive impairment and at least one additional informant. It is important to gather information about the onset, course, and nature of memory and other cognitive impairments and any associated behavioral, medical, or psychological issues, including comorbid medical conditions, alcohol and other substance use, vision and hearing problems, and depression.

The primary care team should also ask about recent illnesses, falls, head injury, prescription and over-the-counter medications, unintentional weight loss, and family history of dementia.

Primary care teams may wish to use several assessment tools to evaluate patients for depression, cognition, and function. It is best to conduct cognitive testing using validated assessment instruments that measure multiple cognitive domains (Mattke et al., 2023; Sabbagh, et al., 2020). 

The Mini-Mental State Examination (MMSE) (Folstein et al., 1975) is a well-accepted and commonly used tool among health care professionals to assess cognition. The MMSE is more appropriate for patients with established cognitive impairment and can be used to evaluate the speed of decline over time. Presently, the use of the MMSE is restricted by copyright and can involve fees. Thus, the MMSE is not shown in this toolkit.

Validated instruments to test for delirium and depression that may be used by primary care teams include the Confusion Assessment Method (CAM), the Patient Health Questionaire-9 (PHQ-9), the Geriatric Depression Scale, and the Center for Epidemiologic Studies Depression Scale Revised (CESD-R-20).

When an individual has been diagnosed with dementia, teams should also assess for dementia-related neuropsychiatric symptoms. These might include symptoms such as apathy, depression or anxiety, or more severe symptoms associated with dementia-related psychosis presenting as hallucinations, delusions, or agitation (e.g., physical or verbal aggression, excessive motor activity) (Vik-Mo 2018). The Agitation in Alzheimer’s Screener for Caregivers (AASC) can be used to screen for agitation (Clevenger, 2023). This validated, 1-minute screening tool is based on the International Psychogeriatric Association (IPA) definition (Sano, 2023). If agitation symptoms are identified, provider teams can use Agitation in Alzheimer’s Disease: A Decision Tree for Healthcare Providers from GSA to guide care planning. Additionally, when an individual has dementia caused by certain neurological conditions, the team should be alert for and address symptoms of pseudobulbar affect. More information about these conditions is available at GSA’s webpage on Brain Health, Cognitive Impairment, ADRD. 

Functional impairment is usually assessed by asking the individual and a family member or other informant about the patient’s daily functioning. Commonly used instruments include the Katz Index of Independence in Activities of Daily Living (asks about bathing, dressing, toileting, transferring, continence, and feeding) (Shelkey, 1999); the Instrumental Activities of Daily Living (IADL) Scale (asks about using the telephone, shopping, food preparation, housekeeping, laundry, transportation, and ability to manage medications and finances (Lawton & Brody, 1969); and the Functional Activities Questionnaire (asks about writing checks and other financial management activities; working on a hobby; making a cup of coffee or a balanced meal; keeping track of current events; understanding TV, a book, or a magazine; remembering appointments and medications; and driving or using other transportation) (Pfeffer et al., 1982).

A diagnosis of dementia requires impairment in functioning that is sufficient to interfere with performance of daily activities. If the patient has cognitive impairment but not the required level of functional impairment, a diagnosis of mild cognitive impairment may be more appropriate instead of dementia.

A physical and neurological examination should be conducted to assess walking, gait, balance, coordination, speech and language, vision, hearing, focal weakness, extrapyramidal signs such as rigidity, tremor, or slowness of movement (bradykinesia), blood pressure, and heart and other vascular functions that affect blood flow to the brain.

Neuropsychological testing is helpful in diagnosing mild and very early-stage dementia and evaluating atypical presentations, particularly for patients who have a dual diagnosis or when there is a need to rule out psychological diseases. It can provide comprehensive, objective information about which cognitive functions are affected and establish a baseline for future reevaluations.

Routine laboratory tests are used to rule out treatable causes of cognitive impairment. Suggested tests include the following:

• Complete blood cell count.
• Serum B₁₂.
• Serum calcium.
• Folate.
• Glucose.
• Serum electrolytes.
• Thyroid function.
• Liver function.
• Renal function.

One blood test to aid in the diagnosis of Alzheimer’s disease is on the market; although it is not FDA approved, it has received breakthrough device designation and is available via self-pay (Anderson, 2022). Blood tests are currently not recommended for diagnosing Alzheimer’s disease in primary care settings (Hansson, 2022).

There are rapid advancements in blood biomarker tests of amyloid pathology for use in research and clinical settings. In June 2024, the Global CEO Initiative on Alzheimer's Disease Blood-Based Biomarker Workgroup published its recommendations, "Acceptable performance of blood biomarker tests of amyloid pathology - recommendations from the Global CEO Initiative on Alzheimer's Disease." These consensus guidelines developed by representatives of over 90 communities of interest establish minimum performance standards to ensure the accuracy and reliability of blood-based biomarker tests for Alzheimer's and aim to help drive more accessible, accurate, and timely diagnosis of Alzheimer’s disease. The American Academy of Family Physicians and GSA conducted compatible surveys to their members to assess clinician awareness, attitudes, and readiness to use blood tests for an Alzheimer's diagnosis. The key takeaways from this survey are summarized in this infographic. The survey results reinforced the importance of performance standards and integration into clinical practice. GSA received funding from the Global CEO Initiative to conduct the GSA survey.

Structural imaging is important in the diagnostic evaluation for dementia, however recommendations for when to use specific assessments vary. Some sources say that structural neuroimaging with a non-contrast computed tomography (CT) or magnetic resonance imaging (MRI) scan should be included to rule out other disease processes. Others say that neuroimaging should be limited to particular clinical situations—for example, when the history and/or physical and neurological examinations indicate a possible central nervous system lesion and for patients who have atypical symptoms or sudden onset of dementia symptoms that could indicate a tumor, subdural hematoma, or normal pressure hydrocephalus.

SPECT (single-photon emission computed tomography) and FDG-PET (fluorodeoxyglucose positron emission tomography) scans are not currently recommended for use in routine clinical diagnostic evaluations for dementia. However, diagnostic practices vary in different medical settings and these tests may be used in routine clinical dementia evaluations in some locations.

FDG-PET scans are currently approved by the Centers for Medicare & Medicaid Services (CMS) for patients who meet specified criteria: they must have a recently established diagnosis of dementia with cognitive decline documented for at least 6 months; meet diagnostic criteria for both Alzheimer’s disease and frontotemporal dementia; and have already been evaluated for specific alternative degenerative diseases or causative factors. Medicare also covers FDG-PET in CMS-approved clinical trials that focus on the utility of FDG-PET in the diagnosis or treatment of mild cognitive impairment or early dementia.

With the approval of infusion therapies for Alzheimer's disease, CMS has expanded access for beta-amyloid PET scans (CMS, 2023). There are ongoing clinical studies to demonstrate the value of beta-amyloid PET and tau PET imaging in increasing the accuracy of the diagnostic process and in improving patient management. Results from a multicenter study of more than 11,000 Medicare beneficiaries suggested that amyloid PET imaging can be impactful in both areas (Rabinovici et al., 2019). These tests may be most appropriate for use in the specialist setting (Johnson et al., 2013).

Although much of the care for people with dementia is managed by primary care providers, referral to a specialist—such as a neurologist, geriatric psychiatrist, neuropsychologist, geriatrician, nurse practitioner with geropsychiatric experience, or a memory disorders clinic—should be considered in situations where there is:

• Diagnostic uncertainty following a standard diagnostic evaluation.
• An atypical presentation, including abnormalities on neurological exam.
• Onset of symptoms in patients younger than 60 years of age.
• A request for a second opinion by the older adult or a family member. 
• Conflict among family members about the diagnosis.
• Potential for the person to be a candidate for disease-modifying treatments.

In addition, providing an accurate diagnosis can be quite challenging and may require more than one visit and referral to a specialist.