Determining a Diagnosis
In trying to determine what is happening, the doctor or medical professional must first review the important signs and symptoms with the patient and caregivers. Follow up tests may be ordered as well.

An accurate diagnosis made after ruling out other possible explanations is essential for successful treatment or management of any disease. As new medical treatments become available, early intervention will be more and more important. Regardless of medical treatments, the sooner patients and caregivers have an accurate diagnosis, the sooner they can plan for upcoming care. The steps listed below are the common steps a person will go through when being evaluated for memory loss, behavioral disorders and other related problems.

Neurological Exam & History

Because memory loss, behavioral disorders and other related problems are often complex, a comprehensive evaluation is necessary. At the UCSF Memory and Aging Center, patients undergo extensive neurological, neuropsychological and nursing assessments that usually requires several hours. Information from the caregiver is sought in every case. The evaluation may require two to three visits to determine the cause of the symptoms and recommend treatment.

After the evaluation, the medical team involved with each patient meets to discuss the diagnosis and potential treatments. After this meeting, the team discusses its findings with the patient and the family. In some cases, a diagnosis will be deferred until more information from blood tests or brain imaging is collected.

Neuropsychological Testing

Neuropsychological testing adds to the clinical assessment of a person. These tests evaluate behavior, language, visuospatial abilities, memory, abstraction, planning and mental control, motor skills and intelligence. The patterns of strengths and weaknesses in a person help identify which areas of the brain are functioning well and which ones are doing poorly.

  • Tests of a person with frontotemporal dementia (FTD) may show visual and memory abilities intact. However, abstract thinking, word generation, motivation and ability to follow rules may be disrupted.

Laboratory Tests

Certain blood tests can help evaluate for treatable conditions that may be contributing to changes in thinking or memory. Some of the most common blood tests ordered as part of a diagnostic evaluation for someone with changes in thinking or memory include: CBC (complete blood count), CMP (comprehensive metabolic panel), TSH (thyroid stimulating hormone), vitamin B12, RPR (rapid plasma reagin), HIV (human immunodeficiency virus).

Neuroimaging

Structural Scans

One of the most useful tests in the evaluation of dementia is magnetic resonance imaging (MRI). MRI uses magnetic fields and radio waves, without any X-rays, to produce images of the inside of your body. It is non-invasive and considered very safe, but some people with metal implants and cardiac pacemakers are unable to have MRIs. Talk to your doctor or the imaging technician if you have any concerns about entering the magnet. Some people find lying in the scanner produces anxiety or claustrophobia because of the tube-like shape or the loud sounds during the scan. Sedation may be available to you if needed, but relaxation techniques like deep breathing, visualization and meditation can also help. Some MRI scanners allow you to listen to music or watch a movie. To get the best pictures, you need to be as still as possible while in the scanner.

A computed tomography (CT) scan is similar to the MRI but does not image brain structure with the fine precision of MR. A CT scan is an X-ray technique that produces cross-sectional images of the inside of your body or head. Typically scans last only a few minutes, during which time you should lie still. You may hear some whirring and clicking noises during this test, which is normal. In order to make the CT image, you will be briefly exposed to X-ray radiation, so be sure to discuss any concerns you have with your doctor.

Functional Scans

A SPECT scan shows how blood flows through arteries in the brain. A radioactive material (tracer) is injected into a vein in the arm, and then the scanner detects the movement of the tracer through the brain and computes the brain activity. Brain areas affected by disease typically show diminished activity. As with any neuroimaging procedure, you will need to lie as still as possible so that the machine can obtain accurate pictures. After the scan, be sure to drink plenty of fluids. Most of the radioactive tracer leaves your body through your urine within a few hours after your SPECT scan. Talk to your doctor if you're concerned about your exposure to radiation during a SPECT scan.

Functional MRI (fMRI) is a special type of scan done in the MRI scanner. It shows changes in blood flow in the brain, which represents areas of the brain using more or less blood to perform certain tasks. The experience and equipment are similar to that of a structural MRI scan.

PET scans show the activity of tissues by measuring the energy usage (metabolic activity) of your brain. Like a SPECT scan, PET combines a brain camera and a radioactive material (tracer). The tracer is what allows doctors to see how your body tissues absorb and use different chemicals in real-time. 30–45 minutes prior to the scan, a tracer is injected into your bloodstream. Once the tracer has had time to reach your brain, you'll lie on a table that moves slowly through the scanner. By detecting metabolic changes in the brain, your doctor can see which areas are healthy versus dysfunctional. Be sure to remain as still as possible so that the machine can get accurate pictures. Depending on the information your doctor needs, you may be asked to perform certain tasks like reading or speaking to activate specific areas of your brain. Once the scan is complete, be sure to drink plenty of fluids to flush out any tracer left in your body. Amyloid imaging with PET can tell whether the patient has a buildup of amyloid protein, a sign of Alzheimer’s disease. New tracers to show the buildup of tau protein buildup are under development, but not yet available.

Cerebrospinal Fluid (CSF) Exam

A doctor collects cerebrospinal fluid (CSF – the watery liquid that surrounds your brain and spinal cord) by doing a lumbar puncture (spinal tap) in which a very thin needle is gently inserted into your lower back between two vertebrae, the bony structures that make up your spine. The procedure usually is done in a doctor’s office and takes about 30–45 minutes, during which time it is important to remain still. Afterward, drink plenty of fluids to help prevent ‟lumbar puncture headache.” If you have a headache or develop a fever after a lumbar puncture, let your doctor know immediately, as there are things that can be done to make the headache go away.

Once the CSF has been collected, many different tests may be ordered to either rule out or investigate the possibility of various conditions. For instance, an elevated white blood cell count in the CSF may suggest a possible infection or inflammatory condition. Other CSF protein tests include neuron-specific enolase (NSE) and total tau protein (T-tau). So far, the data suggest that MRI and PET are better at identifying disease biomarkers, but CSF tests may indicate a rapid injury to nerve cells in the brain.

  • In all cases of rapidly progressive dementia, a CSF examination should be performed. In people with Creutzfeldt-Jakob disease (CJD), the results of the CSF test are usually normal, with the exception of a slightly increased total protein count. If there is an increased white blood cell count, your doctor should consider other neurological diseases, particularly infections such as encephalitis.
  • Although we cannot yet detect prions in the CSF of patients with CJD, detection of elevated levels of the 14-3-3 protein in the CSF has been reported to support a CJD diagnosis in the scientific literature. The UCSF doctors do not feel this test is a very good diagnostic test for CJD because many people with confirmed CJD have a negative or normal result, and many others who do not have CJD but have another neurological disease, have a positive result. Only half of the patients diagnosed with CJD at UCSF have an elevated 14-3-3 protein. Furthermore, in about ⅓ of patients referred to UCSF with an elevated 14-3-3 protein, UCSF doctors identify another diagnosis, not CJD! In many cases, these other diagnoses are very treatable.

Lumbar punctures are also vital to our research efforts at the Memory and Aging Center. CSF collected through lumbar punctures is a primary source to measure markers from the brain in living humans. We now have reliable CSF markers for early detection of Alzheimer’s disease in the clinic and many more markers in exploratory stages to help us better understand how the brain ages and how neurodegenerative disease unfolds in humans. If you are interested in participating in a lumbar puncture as part of a research study, please read the FAQ below or click here.

EEG

An electroencephalogram (EEG) shows patterns of electrical activity produced by your brain as recorded by electrodes placed on your scalp. It is non-invasive and minimally uncomfortable (the electrodes may scratch or itch you and are held in place with a sticky paste). The electrodes do not generate any electricity; they only record electrical activity produced by your brain. You will need to be still with your eyes closed during the 20–40-minute recording in order to get a quality EEG.

  • In people with frontotemporal dementia (FTD), the EEG is usually normal or shows mild frontal slowing. Thus, a normal EEG does not mean that the behavioral manifestations are primarily the result of a psychiatric illness.

Other Issues to Rule Out Before Diagnosing a Neurodegenerative Disease

  • Reactions to medications. Some medications have side effects that mimic the symptoms of dementia. Even a single dose of a medicine may trigger such a reaction in an older person or in someone whose liver fails to eliminate the drug normally. Interactions among two or more drugs may lead to reversible symptoms of dementia as well.
  • Metabolic abnormalities. Decreased thyroid function (hypothyroidism) can result in apathy or depression that mimics dementia. Hypoglycemia, a condition in which there isn’t enough sugar in the bloodstream, can cause confusion or personality changes. Pernicious anemia caused by an inability to absorb vitamin B-12 also can cause cognitive changes. Similarly, changes in blood sodium, calcium, heavy metals or other compounds can cause a reversible dementia.
  • Nutritional deficiencies. Chronic alcoholism can be associated with deficiencies of thiamin (vitamin B-1), which can seriously impair mental abilities. Severe deficiency of niacin (vitamin B-3) may cause pellagra, a neurological illness with features of dementia. Dehydration also can cause confusion that may resemble dementia.
  • Emotional or psychiatric problems. The confusion, apathy and forgetfulness associated with depression are sometimes mistaken for dementia, particularly in older individuals. Depression is not common in people with frontotemporal dementia (FTD), but apathy and emotional withdrawal are and this can lead to the misdiagnosis of depression. Even though people with FTD may appear to be depressed, when you ask them about their mood, they often offer that they feel happy. Similarly, bipolar disorder, schizophrenia and obsessive-compulsive disorder can be misdiagnosed as FTD.
  • Infections. Meningitis and encephalitis, which are infections of the brain or the membrane that covers it, can cause confusion, memory loss or sudden dementia. Untreated syphilis can damage the brain and cause dementia.
  • Normal-pressure hydrocephalus. If cerebrospinal fluid builds up in the ventricles of the brain, the brain tissue is compressed even though the fluid pressure remains normal. This may cause dementia. If this condition is identified in time, it may be treated by draining the excess fluid via a tube (shunt).