DIAGNOSING ALZHEIMER’S DISEASE
Clinical diagnosis of Alzheimer’s disease is usually made during the early stage, when the person appears to be physically healthy but is having increasing difficulty making sense of the environment. The affected person and the family may mistake early signs of Alzheimer’s for normal age-related changes. Deciding to seek diagnostic testing can be a major hurdle for the person and the family. Admitting that there may be the possibility of a diagnosis of Alzheimer’s disease can be difficult to accept.
There is no single test that can diagnose Alzheimer’s disease. Various approaches and tools are used to assist in making a diagnosis. Dementia can almost always be determined, but it may be difficult to identify the exact cause. Diagnosis is made using the following tools:
- Patient medical history
- Physical examination
- Neurological examination
- Mental cognitive status tests
- Diagnostic tests (to rule out other health issues that can cause similar symptoms to dementia)
- Brain imaging
(Alzheimer’s Association, 2021b)
Patient Medical History
The patient medical history helps to assess past and current health status and includes:
- Patient age and gender
- Chief complaint
- History of the current complaint
- Past medical history
- Current health status
- Psychosocial history such as marital status, living conditions, employment, sexual history, significant life events, diet, nutrition, and use of alcohol or other drugs
- Family medical history, including Alzheimer’s disease or other dementias
- Review of systems to ask questions about current symptoms not included in the chief complaint
- Mood assessment to detect depression or other mood disorders that can cause memory problems, apathy, and other symptoms that can overlap with dementia
- Review of all medications
(Alzheimer’s Association, 2021b)
Physical and Neurological Examinations
The physical and neurological examinations enable the clinician to assess the overall physical and neurological condition of the patient and provide more information about the current problem, helping to determine an appropriate plan of treatment. The physical exam may be a complete head-to-toe exam or a more focused examination, depending on the chief complaint. It generally includes:
- Overall appearance
- Vital signs
- Heart and lungs
- Head and neck
- Abdominal exam
- Extremities
- Specific exams for male and female
The neurological examination involves evaluating the person for problems that may suggest brain disorders other than Alzheimer’s, which could include Parkinson’s disease, brain tumors, or buildup of fluid in the brain. The exam includes:
- Cranial nerve testing
- Reflex testing
- Coordination
- Motor function and balance
- Gait
- Speech
- Muscle tone and strength
- Eye movement
- Sensory exam
(Alzheimer’s Association, 2021b)
Mental Cognitive Status Testing
A thorough mental status examination evaluates the following cognitive spheres:
- Attention and concentration
- Memory
- Language
- Visuospatial perception
- Praxis (cognitive ability to do complex motor movements)
- Calculations
- Executive functioning
- Mood and thought content
There is currently no cognitive assessment tool that is considered to be a gold standard. The most widely used tools are the Mini-Mental State Exam and the Montreal Cognitive Assessment.
MINI-MENTAL STATE EXAM (MMSE)
The Mini-Mental State Exam is the most popular and well known of mental status screening tests. It assesses multiple cognitive domains, particularly memory and language, which may be most relevant to dementia due to Alzheimer’s disease. The MMSE can be performed in a relatively short time period (5–10 minutes) and is most sensitive to patients at the mild to moderate stage of Alzheimer’s dementia. The tool consists of brief questions and simple tasks scored on a 30-point scale. It cover a wide range of functions, including memory, attention, orientation, and overall executive function.
Advantages of the MMSE include brevity and ease of administration. Disadvantages include the narrow scope, inability to detect subtle memory losses, and interpretation complexity. Such complexity is due to the fact that education and cultural background affect scores (Alzheimer’s Association, 2021b; Slavych, 2019).
MMSE QUESTIONS AND SCORING
During the MMSE, a health professional asks the patient the following questions or instructs the patient to perform a task:
- What is the date today? (3 points)
- What is the season? (1 point)
- What day of the week is it? (1 point)
- What town, state, and country are we in? (3 points)
- What is the name of this place? (1 point)
- What floor of the building are we on? (1 point)
- I am going to name three objects. After I have said them, repeat them back to me. Remember what they are because I will ask you to name them again in a few minutes: apple, table, penny. (3 points)
- I am going to spell a word forward and I want you to spell it backwards. The word is W-O-R-L-D. (5 points)
- What are the three objects I asked you to remember a few moments ago? (3 points)
- What is this called (showing the patient a watch)? (1 point)
- What is this called (showing the patient a pencil)? (1 point)
- Please repeat the following: No ifs, ands, or buts. (1 point)
- Please read the following and do what it says, handing the patient a card that says, “Please Close Your Eyes.” (1 point)
- Please write a sentence. (1 point)
- Please take this piece of paper in your right hand, fold it in half with both hands, and put it in your lap. (3 points)
- Please copy this drawing (showing the patient a drawing of two overlapping pentagons). (1 point)
The maximum MMSE score is 30 points. A score of 20 to 24 suggests mild dementia, 13 to 20 suggests moderate dementia, and less than 12 indicates severe dementia. On average, the MMSE score of a person with Alzheimer’s declines about two to four points each year (Dementia Care Central, 2021a).
MONTREAL COGNITIVE ASSESSMENT (MoCA)
The Montreal Cognitive Assessment is a 30-point test that assesses short-term memory recall, visuospatial ability, and different aspects of executive function. It takes about 10 minutes to complete, with a score of 26 or above considered normal.
Advantages of the MoCA include its sensitivity as a screening tool for mild cognitive impairment, Alzheimer’s disease, and dementia, as well as ease of use. The disadvantage of the MoCA for practitioners is the length of time required for administration (Mendez, 2021; Slavych, 2019).
ST. LOUIS UNIVERSITY MENTAL STATE EXAM (SLUMS)
The St. Louis University Mental State exam consists of 11 brief questions scored on a 30-point scale. It takes approximately 7–10 minutes to administer, and the questions cover a wide range of functions, including memory, attention, orientation, and overall executive functions.
Both the MMSE and SLUMS have a total of 30 points, however, the average score of the SLUMS is approximately 5 points lower than that of the MMSE, supporting the belief that the SLUMS is a more difficult test and thus likely to be more sensitive to mild cognitive impairment, picking up any issues sooner (Rosenzweig, 2021).
COMPUTERIZED TESTS
The U.S. Food and Drug Administration has cleared several computerized cognitive testing devices for use. These are the:
- Cantab
- Cognigram
- Cognivue
- Cognision
- Automated Neuropsychological Assessment Metrics (ANAM)
The advantages of using computerized tests include the fact that tests are given exactly the same way each time, and using both clinical tests and computer-based tests can give clinicians a clearer understanding of cognitive differences experienced by their patients. Despite concerns regarding elderly patients’ computer literacy, there are high completion rates, and patients have generally positive experiences completing them. The Cantab, for example, is intuitive to use, and its game-like nature is engaging and motivating (Alzheimer’s Association, 2021b).
INFORMANT QUESTIONNAIRES
Informant- or caregiver-completed questionnaires can also be employed to assess a patient for cognitive impairment. These include asking an informant who knows the patient well to answer a series of questions about the patient’s memory and other cognitive functions. Three such questionnaires are:
- Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)
- Alzheimer’s Disease Caregiver Questionnaire
- AD8 Dementia Screening Interview
MEDICARE ANNUAL WELLNESS VISIT
Medicare’s Annual Wellness Visit (AWV) benefit requires, among other things, an assessment to detect cognitive impairments. Along with routine measurements and health risk assessment, during this visit functional ability and level of safety are assessed, as well as ability to perform activities of daily living. Screening is included for cognitive impairment and depression. Dementia rates have increased with AWV implementation, with varying effects by race and ethnicity (Lind et al., 2021).Diagnostic Testing
Laboratory tests are performed to rule out other potentially reversible forms of cognitive impairment.
Test | Associated With |
---|---|
(Lakhan, 2021; OneCare Media, 2021) | |
Folate level | Folate deficiency |
Vitamin B12 | Vitamin B12 deficiency |
Thyroid stimulating hormone (TSH) and T4 | Thyroid disease |
Complete blood count (CBC) | Anemia, infection |
Electrolytes | Renal disease, dehydration |
Glucose level | Diabetes |
Urinalysis, microscopy and culture | Urinary tract infection |
Liver enzymes | Hepatic disease |
C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) | Inflammatory processes |
HIV antibody | HIV/AIDS |
Rapid plasma reagin (RPR), venereal disease research laboratory (VDRL) | Syphilis |
Toxicology screening | Illicit drug use, alcohol use |
Paraneoplastic antibodies | Autoimmune encephalitis |
Less Common Tests | Purpose |
Cerebrospinal fluid (CSF) biomarkers: beta-amyloid, total tau protein, and phosphorylated tau | Confirm or rule out Alzheimer’s disease |
ApoE genotype | Confirm or rule out probable Alzheimer’s disease |
PSEN1, PSEN2, and APP | Genetic mutations |
BLOOD TEST FOR ALZHEIMER’S DISEASE
An international research team has developed a 19-protein biomarker panel blood test for early detection and screening of Alzheimer’s disease, with an accuracy level of over 96%. This test can also differentiate among the early, intermediate, and late stages of the disease and can be used to monitor the progression of the disease over time. The findings serve as a foundation for the development of a high-performance, blood-based test for AD screening and monitoring in clinical settings (Jiang et al., 2021).
ELECTROENCEPHALOGRAM (EEG)
EEG may be done to detect abnormal brain-wave activity. EEG is usually normal in people with mild Alzheimer’s disease and many other types of dementia. But abnormalities do occur in delirium and Creutzfeldt-Jakob disease, another cause of dementia (Helpguide.org, 2021).
Imaging Studies
Imaging studies are particularly important for ruling out treatable causes of progressive cognitive decline.
STRUCTURAL IMAGING
Magnetic resonance imaging (MRI) and computed tomography (CT) scans are the structural imaging techniques most commonly used in conducting diagnostic studies to determine a diagnosis of dementia. Structural imaging visualizes physical alterations in the brain that occur with aging and in various disease states. MRI is much preferred over CT for evaluation of dementia, as it allows for a broader range of brain tissue properties to be studied while avoiding exposure to potentially harmful ionizing radiation. However, CT scan is the best choice when a patient is too claustrophobic to undergo an MRI, has a pacemaker or ferromagnetic implant, or is unable to remain still long enough to tolerate the more time-consuming MRI.
MRI is able to identify structural changes, including patterns of atrophy that characterize neurodegenerative disease and also shrinkage in specific brain regions such as the hippocampus, which may be an early sign of Alzheimer’s disease. However, structural imaging is not used to diagnose Alzheimer’s, as there is currently no agreed-upon standard values for brain volume that would establish the significance of a specific amount of shrinkage for any individual person at a single point in time.
The primary objectives of structural neuroimaging are to rule out potentially treatable causes of progressive cognitive decline, such as stroke, small vessel disease, tumors, or hydrocephalus, and to assess specific causes (i.e., neurodegenerative or otherwise) of dementia (Alzheimer’s Association, 2021b; Lakhan, 2021).
FUNCTIONAL NEUROIMAGING
Functional neuroimaging enables in vivo (within a living organism) examination of how the brain functions. Functional MRI (fMRI) may detect abnormalities within the brain that cannot be found with other imaging techniques. FMRI can detect or measure changes in metabolism, blood flow, regional chemical composition, and absorption.
Blood flow to an area of the brain is very sensitive to changes in neural activity. This makes it possible to map changes in neural activity associated with a wide range of motor, sensory, and cognitive skills. The fMRI is done by exposing patients to a stimulus or having them engage in a cognitive activity while acquiring single-shot images of the brain. The region of the brain that is responding to the stimulus or is engaged in the activity will experience an increase in metabolism.
Research studies have found that fMRI scanning may inadequately represent an individual’s typical brain activation pattern, particularly an individual with dementia. Therefore, multiple imaging baselines are recommended for comparison (UW, 2021; Paek et al., 2019).
MOLECULAR NEUROIMAGING
Molecular imaging provides detailed pictures of what is happening inside the body at the molecular and cellular level. Modalities include positron emission tomography (PET) and single photon emission computed tomography (SPECT). Both are nuclear medicine techniques that use small amounts of intravenously injected ionizing radiation in the form of short-lived radioisotopes (radiotracers) so that activity in the brain or other organs can be studied to diagnose and determine the severity of a variety of diseases. PET and SPECT can help narrow down a diagnosis by revealing deficits common in Alzheimer’s disease that are distinct from findings for other dementias, such as frontotemporal lobar degeneration and dementia with Lewy bodies.

PET scans of the brain. (Source: National Institute on Aging/National Institutes of Health.)
A combined PET/CT exam fuses images from a PET scan and CT scan to provide details on both the anatomy from the CT scan and function of organs and tissues from the PET scan. A PT/CT scan can help differentiate Alzheimer’s disease from other types of dementia.
An amyloid PET scan visualizes plaques present in the brain. Before amyloid PET, these plaques could only be detected by examining the brain at autopsy. Amyloid PET scanning makes amyloid plaques light up on a brain PET scan, enabling accurate detection of plaques in living people (SNMMI, 2021; USFC, 2021d).
Functional Assessment
Dementia is characterized by cognitive deficits that cause functional impairment to basic and instrumental activities of daily living. Functional status can be assessed by use of a validated tool, direct examination of the patient, or obtaining information from a knowledgeable informant (i.e., family member or friend who routinely observes the person in his or her day-to-day activities). An assessment of the patient’s functional status should include, at minimum, an evaluation of the ability to perform instrumental activities of daily living (IADLs) (i.e., preparing meals, managing finances, etc.) and basic activities of daily living (ADLs) (i.e., eating, dressing, etc.).
As Alzheimer’s progresses, periodic assessment of the patient’s ability to function should be carried out. Functional status can also be assessed using one of a number of valid and reliable instruments. Examples include:
- Lawton Instrumental Activities of Daily Living Scale
- Barthel ADL Index
- Katz Index of Independence in Activities of Daily Living
- Functional Activities Questionnaire (FAQ)
FUNCTIONAL ACTIVITIES QUESTIONNAIRE (FAQ)
The FAQ is efficient to administer, taking 10 minutes or less to complete. It evaluates activities of daily living and is completed by an informant who spends at least two days a week with the person and rates the person in the following 10 areas:
- Writing checks and maintaining other financial records
- Assembling tax or business records
- Shopping alone for clothes, household necessities, or groceries
- Playing a game of skill or working on a hobby
- Heating water for coffee or tea, turning off the stove
- Preparing a balanced meal
- Keeping track of current events
- Paying attention to and understanding a TV show, book, or magazine
- Remembering appointments, family occasions, holidays, or medications
- Traveling out of the neighborhood (e.g., driving or arranging to take the bus)
FAQ Rating:
- 3 points if dependent on others to complete the activity
- 2 points if requires assistance to complete the activity
- 1 point if has difficulty with the activity, but performs independently
- 1 point if never performed the activity and would have difficulty now
- 0 points if performs the activity independently with no difficulty
- 0 points if never performed the activity but could do so now
Scoring:
- Scores range from 0 to 30, with higher scores indicating more functional difficulty.
- Scores higher than 10 suggest reduced functional ability.
(AMA, 2019)