Neuroimaging in the Diagnosis of Dementia

Mark P. Bowes, PhD

  ^*Medical Writer, Portland, Oregon.
  Address correspondence to: Mark P. Bowes, PhD, Medical Writer, 7135 SE 18th Avenue, Portland, OR 97202. E-mail: mpbowes@gmail.com.

Disclosure Statement: Dr Bowes reports having no significant financial or advisory relationships with corporate organizations related to this activity.

ABSTRACT

Dementia is the gradual and progressive loss of cognitive ability that is caused by disease or injury of the brain. Many neurologic disorders can cause symptoms of dementia, including Alzheimer disease (AD), Parkinson disease, stroke, and other neurodegenerative diseases. Dementia is common in radiology practice, and patients with cognitive impairments are often seen in the imaging facility. Patients with cognitive impairments can present unique challenges, but neuroimaging is often an essential step in establishing a correct diagnosis and selecting an appropriate treatment option. Structural neuroimaging techniques such as computed tomography or magnetic resonance imaging are essential in identifying potentially reversible causes of cognitive impairment, such as a tumor or bleeding at the surface of the brain. These structural approaches are generally recommended as an early step in the diagnosis of cognitive impairment for most patients, in combination with biochemical tests to rule out other potentially treatable diseases (eg, kidney disease or infection). More recently, functional neuroimaging techniques such as positron emission tomography or single photon emission computed tomography (SPECT) have been applied to the diagnosis of cognitive impairment. These techniques make it possible to visualize physiological processes within the brain, such as glucose utilization of blood flow, and have proven valuable in distinguishing different types of dementia from one another. AD, the most common type of dementia, affects more than 4 million people in the United States, or at least 70% of individuals with dementia. A definitive diagnosis of AD requires the demonstration of characteristic pathology on microscopic examination of brain tissue. However, most patients with AD are diagnosed on the basis of clinical signs and symptoms, combined with structural imaging findings that rule out other potential causes of cognitive impairment. Vascular dementia is the loss of cognitive function that occurs when brain tissue is damaged by decreased blood flow. Vascular dementia often follows a stroke, but it can also be a slow and gradual process that develops after a series of smaller, "silent" strokes. Dementia with Lewy bodies (DLB) has only recently been recognized as a common form of dementia. DLB may be difficult to distinguish from AD, but recent research has examined potential imaging methods that may be used to identify patients with DLB with a high degree of accuracy. Frontotemporal dementia is a relatively rare cause of cognitive impairment that often affects younger patients. Effective communication strategies are essential to attain the best possible imaging results when working with older patients who have cognitive impairments or other common medical problems.

Introduction
Dementia is the gradual and progressive loss of cognitive functioning that is caused by disease or injury of the brain. The diagnostic criteria for dementia include significant memory impairment and at least 1 other cognitive symptom, such as impaired speech or decreased ability to perform complex tasks.¹ A diagnosis of dementia also requires that the decline in cognitive functioning is severe enough to significantly interfere with the individual's ability to function normally in social settings or at work. The symptoms of cognitive impairment must be distinguished from delirium, which is a state of altered consciousness (eg, decreased alertness or attention) that usually develops over a relatively short period of time in conditions such as acute illnesses or drug or alcohol intoxication. Finally, it must be established that cognitive impairment is not caused by some kind of potentially reversible brain injury, such as a tumor or bleeding at the surface of the brain, or another potentially reversible medical condition such as kidney or thyroid disease.

Dementia is a very common condition in radiology practice, and several neuroimaging techniques are part of the standard workup for patients with cognitive impairment. Individuals with dementia may present several distinct challenges in the imaging facility due to their generally older age and their problems remembering and following instructions. However, the use of neuroimaging techniques to establish an accurate diagnosis is an essential step in developing a treatment plan that will help to improve quality of life for the patient and the patient's family. Although there is no cure for dementia, appropriate treatment can help to slow the progression of disease and prolong the patient's independence and ability to function.^2,3

The Impact of Dementia
Dementia is a common symptom among the elderly, affecting as many as 10% of individuals over the age of 65.⁴ The effects of dementia include not only decreased memory or other cognitive abilities, but also impairments of social or occupational function, decreased ability to carry out normal activities of daily living, and a significant burden on family members or other caregivers.⁵ Dementia is encountered in several medical conditions that are more common among older patients, such as Alzheimer disease (AD), Parkinson disease, and stroke. However, dementia is also encountered in some younger patients who have early onset AD (defined as onset of dementia before age 65), or in other relatively uncommon conditions.⁶ It is important to understand that dementia is not the same as normal age-related changes in memory or intellectual functioning. Although many older individuals experience some degree of memory loss or other minor impairments of cognitive function as a part of the normal aging process, dementia is a much more severe and persistent decline in mental ability. Dementia may be clearly documented using standard tests of memory or intellectual functioning, whereas these objective measures of impairment are absent or very mild in individuals with normal age-related cognitive changes.⁷ Dementia is not an inevitable result of old age, and many very elderly individuals never develop dementia.

It is also important to distinguish dementia from mild cognitive impairment (MCI), a related condition that has been described as a transitional state between normal age-related decreases in cognitive function and the more severe cognitive impairments of dementia.⁷ People with MCI may have problems with memory, language, or other cognitive abilities, but they do not have severe impairments in their ability to carry out normal activities of daily living.^8,9 It has been estimated that MCI affects approximately 20% of individuals over the age of 65, and nearly 30% of individuals over the age of 85.¹⁰ People with MCI are at increased risk of progressing to AD or another type of dementia over the next few years, although many of those with MCI never develop dementia.

Diagnosing Dementia
Treatment recommendations may vary significantly for patients with different types of dementia. Accurate diagnosis of cognitive impairment is therefore an essential step in ensuring that the patient receives appropriate treatment. For example, AD is often treated using a family of drugs known as cholinesterase inhibitors. These medications increase the activity of the neurotransmitter acetylcholine within the central nervous system (CNS). Acetylcholine is produced and released by nerve cells that are required for normal functioning of long-term memory, and the loss of these acetylcholine-producing neurons has long been recognized as an important pathologic feature of AD.¹¹ In contrast, a patient with vascular dementia may require an intensive program to modify risk factors for cardiovascular disease in order to prevent stroke.

In 2001, the American Academy of Neurology (AAN) published a set of standard guidelines for the diagnosis of dementia.⁴ These guidelines emphasized that decreased cognitive functioning may be caused by many different conditions, and they recommended that all patients with cognitive impairment should be screened for common and potentially reversible conditions that can cause memory loss or other symptoms of cognitive impairment (Table).⁴ Intellectual functioning is often evaluated using several standard neuropsychological tests, and 3 of these tests are especially common for the diagnosis of dementia: the mini mental state examination (MMSE), the clock drawing task, and the Blessed Dementia Scale.¹² The MMSE consists of a series of questions that evaluate the patient's orientation to space and time (eg, "What is the day of the week" or "Where are we now?"), the ability to recall a list of unrelated items after a short delay, to perform simple mental calculations (eg, counting backwards from 100 by 7), to copy a simple figure, and to follow simple directions. (The full test is available online at: utswfm.googlepages.com/NH_MMSE.pdf.) The MMSE is scored on a scale from 0 to 30, with higher scores indicating better cognitive functioning. The meaning of a particular score on the MMSE depends somewhat on the patient's age and level of education, but a score less than 24 usually indicates cognitive impairment. In the clock drawing test, the patient is asked to draw the face of a clock showing a particular time (eg, 10 minutes after 11).¹³ Individuals with dementia have considerable difficulty with this task: they may incorrectly place the numbers and hands, omit or duplicate numbers, or make other errors that indicate cognitive impairment. The clock drawing test is a good choice for patients with language, hearing, or cultural barriers that may complicate the use of the MMSE.¹² Finally, the Blessed Dementia Scale evaluates the patient's ability to carry out normal activities of daily living (eg, to perform household tasks or handle small amounts of money), and it also includes questions about recent changes in habits or personality.¹⁴ Individuals with dementia do not generally exhibit a uniform, global loss of cognitive function that affects all domains of intellectual ability. Most patients have impairments in certain specific areas of cognitive function whereas other types of functioning are well preserved. The specific pattern of cognitive impairments often provides important clues about the diagnosis of the particular dementia subtype. For example, individuals with dementia that is caused by brain lesions affecting the cerebral cortex often have pronounced memory and language impairments, whereas patients with brain lesions affecting the subcortical areas of the brain may have less severe language impairment, but they may also have impairments of sensory or motor function, apathy, or depression.^15,16

Structural and Functional Neuroimaging Techniques in the Diagnosis of Dementia
According to the AAN dementia guidelines, neuroimaging is an important component of the routine diagnosis of dementia.⁴ Several neuroimaging methods are available to identify structural and functional abnormalities of the brain that can cause cognitive impairment in patients with dementia or MCI.¹⁷ Structural imaging techniques such as magnetic resonance imaging (MRI) or computed tomography (CT) are often used to identify potentially treatable conditions that affect the structure of the brain, such as brain tumors, hydrocephalus, or hematomas.¹⁷ These techniques are often useful for the detection of the loss of brain tissue (atrophy) or for the identification of lesions caused by cerebrovascular disease, but they may be less effective for the identification of more subtle signs of early neurologic injury that develop before the appearance of detectable symptoms.¹² CT and MRI each has its own advantages and disadvantages for routine neuroimaging.¹⁷ CT scans are widely available, rapid, provide reasonably good resolution (approximately 1 mm), are relatively inexpensive, and are often used when an image must be obtained as quickly as possible. The use of intravenous contrast material can make it easier to visualize bleeding, tumors, infection, and inflammation.⁷ Radiation exposure is similar to about one half to one third the normal background exposure for a 1-year period.⁷ MRI scans generally provide greater tissue contrast and are more able to visualize small regions of brain injury. T1-weighted images reveal differences between gray matter and white matter, and T2-weighted images are especially useful for identifying white-matter lesions. Gradient echo T2*-weighted images are used to detect very small hemorrhages (known as microbleeds), which are often found in patients with dementia.^18,19 Contrast materials that contain gadolinium are sometimes used to enhance the appearance of brain lesions and to identify areas where the permeability of the blood-brain barrier is increased. MRI scans do not expose the patient to radiation. However, some patients cannot be imaged using MRI because they have metallic implants (such as hip replacements or pacemakers) that cannot be exposed to the high magnetic fields of the scanning device.⁷

Functional imaging techniques measure physiologic processes such as the uptake of glucose by brain tissue or blood flow through the blood vessels of the brain.¹⁹ Two main functional techniques are used most often in the assessment of patients with dementia. F18-fluorodeoxyglucose positron emission tomography (FDG-PET) uses a radioactively labeled glucose tracer to measure tissue glucose uptake. Single photon emission CT (SPECT) uses a radioactive tracer to measure the perfusion of blood through tissues.¹⁹ The spatial resolution of these images is less than MRI (approximately 10 mm for SPECT and 3-5 mm for PET), but by providing techniques to image brain function before atrophy or other structural abnormalities have become visible, they may make it easier to diagnose dementia earlier than conventional structural imaging techniques. This may be helpful in making a correct early diagnosis or in selecting an appropriate treatment to prevent further progression of dementia.⁷ Functional imaging techniques may also use highly specific molecular probes to label particular molecules within the CNS, which are then visualized using PET, SPECT, or other imaging methods. Functional neuroimaging results may also be displayed as an overlay with conventional structural imaging to show the specific regions of physiological activity that are revealed by the functional imaging.¹⁷

Alzheimer Disease
Alzheimer disease is the most common cause of dementia, affecting more than 4 million people in the United States, and 70% or more of all people who have dementia.^20,21 Due to the aging of the US population, it has been projected that the prevalence of AD in the United States may triple over the next 50 years, to more than 13 million people.²⁰ AD may eventually affect 1 out of every 45 Americans.⁵ The early stages of AD are usually characterized by difficulties with memory. Cognitive function gradually and irreversibly worsens over time, eventually progressing to include profound impairments of memory, language, and decision-making ability. Other common symptoms of more advanced AD include sleep disturbances, physical or verbal outbursts, restlessness or pacing, delusions (beliefs in things that are not real), and hallucinations (experiencing things that are not present).²² In advanced AD, patients are unable to carry out the most basic activities of normal daily living. With time, the progressive loss of brain tissue caused by AD interferes with normal brain and bodily functioning, resulting in paralysis, incontinence, respiratory problems, and other complications. AD is always eventually fatal, and the typical life expectancy is approximately 8 to 12 years after diagnosis.¹⁵

Microscopic examination of brain tissue from individuals with AD reveals 2 principal pathologic characteristics that are highly specific to AD. Neuritic plaques are abnormal deposits of the protein β amyloid that are found outside of nerve cells within the CNS. Neurofibrillary tangles are found inside nerve cells and consist of abnormal arrangements of a microtubule protein called tau.²³ It is not known precisely how these pathologic lesions cause the symptoms of AD. The presence of neuritic plaques and neurofibrillary tangles can only be identified by examining a sample of brain tissue, either at autopsy or from a biopsy sample. This is rarely performed, and in actual clinical practice, AD is nearly always diagnosed on the basis of characteristic signs and symptoms after ruling out other potential causes of dementia. Diagnostic rating systems have been developed by the American Psychiatric Association (APA) and by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA).²⁴ Either diagnostic system can be used to diagnose AD with a high degree of accuracy.⁴ In the APA diagnostic system, dementia of the Alzheimer's type is diagnosed by impairment of memory plus at least 1 additional cognitive disturbance: aphasia (language disturbance), apraxia (inability to perform motor activities despite normal motor functioning), agnosia (inability to identify objects despite normal sensory function), or impaired executive function (eg, planning or sequencing). The NINCDS-ADRDA system uses a combination of brain pathology findings and clinical symptoms to rate patients as having definite, probable, possible, or unlikely AD. The diagnosis of definite AD in this system requires the demonstration of AD pathology (ie, the presence of plaques and tangles in a brain autopsy or biopsy sample).

The goal of neuroimaging evaluation for a patient with suspected AD is to identify any underlying structural lesions that might cause the symptoms.⁴ Typical structural neuroimaging examination includes a noncontrast CT or MRI scan at the time of the initial assessment of dementia in order to identify CNS pathology. Neuroimaging of patients with AD often reveals significant atrophy of the cerebral cortex (Figure 1), especially of the temporal lobes, hippocampus, and entorhinal cortex.^4,25 When atrophy is severe, it may produce visible enlargement of the cerebral ventricles (the fluid-filled chambers within the brain) or the sulci (the grooves or indentations that are found across the outer surface of the brain).¹⁷ However, there is often significant overlap between atrophy associated with AD and with normal aging.²⁵ It is also possible for a patient to have AD without any visible atrophy on a CT or MRI scan.¹⁷ Recommended techniques for visualizing atrophy of the parietal lobes include axial or coronal T1 or fluid-attenuated inversion recovery (FLAIR); thinning of the corpus callosum may be viewed using T1 saggital sequences; and atrophy of the hippocampus may be visualized with thin coronal T1 or FLAIR slices through the medial temporal lobe.²⁵

Research studies have suggested that the addition of functional imaging techniques may improve diagnostic accuracy compared to clinical diagnosis alone.²⁵ Functional neuroimaging was not recommended for the routine diagnosis of AD in the 2001 AAN dementia guidelines.⁴ More recently, FDG-PET has become part of routine clinical practice for the early diagnosis of AD and to differentiate AD from a type of dementia known as frontotemporal dementia (FTD; described in more detail below).¹⁷ A pattern of low glucose uptake across much of the cerebral cortex is present in patients with AD when compared to healthy control subjects, and may also be observed in patients who are at risk for AD (eg, patients with MCI or with a family history of AD).¹⁷ Decreased perfusion on SPECT scanning is also observed in patients with AD.¹⁷

As noted previously, AD can only be definitely diagnosed on the basis of microscopic examination of brain tissue. Neuroimaging has traditionally been a valuable technique to establish that the patient is likely to have AD or to rule out other conditions, but is not sufficient to rule in a diagnosis of AD. Some intriguing recent research suggests that this may change in the near future. Researchers at the University of Pittsburgh have developed a radioactively labeled marker—(11)C-Pittsburgh compound B (PIB)—which binds very specifically to the β amyloid that makes up neuritic plaques in patients with AD.²⁶ Preliminary studies have suggested that the use of this marker and related compounds in conjunction with PET scanning may provide a very accurate imaging method to identify β amyloid deposits in the brains of living patients, providing a more definitive diagnosis of AD than is possible clinically but without the need for a biopsy or autopsy sample.²⁷ The use of this technique may also increase the accuracy of differentiating patients with AD from other types of dementia.²⁸ At present, this remains primarily an investigational technology that is being extensively evaluated in many clinical studies.

Vascular Dementia
Vascular dementia is the loss of cognitive functioning due to brain damage that occurs when there is too little blood flow within the brain. Inadequate blood flow is referred to as ischemia, and cerebral ischemia can cause significant loss of neurons and supporting cells. Vascular dementia can be a caused by reduced blood flow to the brain due to blockage of the carotid arteries, by the results of a single stroke, or by the gradual accumulation of brain injury over time due to disease of the small blood vessels of the brain.^15,25 Vascular dementia affects nearly 20% of older patients with dementia, and more than 2% of all Americans over the age of 70.²⁹ In contrast with the steady and gradual decline of function that is typical in AD, patients with vascular dementia are more likely to have an abrupt onset of symptoms and to deteriorate in discrete "steps," although a gradual and progressive course is also possible⁷

The diagnostic criteria for vascular dementia usually require that the cognitive symptoms can be linked to a particular ischemic event, such as a single large stroke or a series of small strokes. For example, vascular dementia may be diagnosed when cognitive impairment occurs within 3 months after a stroke.³⁰ In clinical practice, it can be difficult to identify a specific vascular event that causes symptoms of dementia because some strokes are clinically "silent"—that is, they occur in parts of the brain where they produce symptoms that may be subtle and difficult to recognize.²⁵ In these cases, neuroimaging is often helpful to identify changes in brain structure or function that suggest that the patient has had a silent stroke. Neuroimaging can be used to identify different structural lesions that vary depending on whether the patient had a single large stroke or smaller and more diffuse regions of ischemia. Major neuroimaging findings typically encountered in patients with vascular dementia include^17,25:

• Evidence of 1 or more strokes affecting the large blood vessels of the brain (either a single large stroke or several smaller ones) on MRI evaluation
• Small, clearly defined strokes, generally only a few millimeters in diameter (known as lacunar infarctions)
• Regions of the white matter that appear bright on T2 or FLAIR imaging sequences (known as white-matter hyperintensities or leukoaraiosis)
• Microscopic hemorrhages, which are generally related to hypertension but may also be caused by the same disease process that causes neurodegeneration in AD.

Lacunar infarctions and white-mater hyperintensities are not completely specific for vascular dementia. They also occur to some extent in healthy older people and in patients with other types of dementia.¹⁷ MRI is generally more sensitive than CT for the identification of lesions of vascular dementia¹⁷ Representative imaging findings associated with vascular dementia are shown in Figure 2.³¹

Neuroimaging and autopsy studies have shown that many patients have more than 1 type of dementia at the same time, a clinical presentation that is referred to as mixed dementia. In many cases, these patients have vascular dementia in combination with another dementia type, such as AD.²⁵

Dementia with Lewy Bodies
Until recently, it was generally believed that nearly all patients with dementia had either AD or vascular dementia. It was known that other types of dementia existed, but they were believed to be relatively rare.³² Beginning in the early 1990s, it was increasingly recognized that many individuals actually had another type of dementia—dementia with Lewy bodies (DLB)—and that this disorder was often misdiagnosed as AD. Research over the last decade has demonstrated that DLB is actually fairly common. One study that examined specific markers for AD and DLB in postmortem brain tissue samples from a diverse group of individuals with dementia found evidence of AD in 77% of brain tissue specimens, DLB in 26%, and vascular dementia in 18%. Another 5% had FTD.²¹ These numbers do not add up to 100% because many patients had evidence of more than one type of dementia.

Dementia with Lewy bodies is characterized pathologically by a distinct pattern of microscopic deposits that are visible in brain autopsy or biopsy tissue samples. These deposits, which are known as Lewy bodies, consist of abnormal aggregates of the protein α-synuclein.³³ The clinical symptoms of DLB are also distinct from AD or vascular dementia, and generally include cognitive impairment that fluctuates over time, sleep disturbances, visual hallucinations that often appear very well-formed and real to the patient, and symptoms resembling those of Parkinson disease (such as a shuffling gait, slowed movement, loss of facial expression, or muscle stiffness).³⁰ Patients with DLB often respond well to cholinesterase inhibitors, but they may also exhibit exaggerated responses or even life-threatening adverse reactions when treated with antipsychotic medications, which are sometimes prescribed for these patients to control hallucinations and delusions.³²

Because it has been difficult for clinicians to reliably distinguish DLB from AD on the basis of clinical presentation or history, neuroimaging methods are especially important to correctly diagnose these patients.³² At present, neuroimaging methods for the diagnosis of DLB are not as well established as for AD or vascular dementia. Some characteristic findings that appear to distinguish patients with DLB include less atrophy of the hippocampus or temporal lobes than as usually seen in AD, but decreased perfusion of the occipital lobes on SPECT scanning and decreased occipital lobe metabolism on PET.³² A recent report at the 2009 annual meeting of the Society of Nuclear Medicine suggested that it may be possible to examine the uptake of certain markers by brain tissue during PET scanning to distinguish AD from DLB and to increase the diagnostic accuracy of both conditions compared to a clinical diagnosis.²⁸ In this study, patients with cognitive impairments were first diagnosed clinically by a panel of experts. The patients then underwent PET scanning with 2 different markers: the 11C-PIB compound described previously, for the assessment of amyloid deposits associated with AD; and [11C]dihydrotetrabenazine (DTBZ), which has been described as a specific marker for DLB pathology. PET scans revealed severely decreased uptake of DTBZ in the brains of patients with DLB, but normal 11C-PIB uptake. In contrast, patients with AD had elevated uptake of 11C-PIB indicating the presence of amyloid plaques, but normal DTBZ uptake. In some cases, there was a mismatch between the clinical diagnosis and the imaging findings. If the PET scan results are considered the "true" diagnosis based on brain pathology, these investigators found that 24% of the clinical diagnoses were in error, which is similar to the rate of diagnostic error that has been observed when clinical diagnoses were compared with autopsy findings. These results suggest that there is considerable potential for new imaging technologies to improve the diagnosis of these common types of dementia in comparison with standard clinical methods that are widely used today.

Frontotemporal Dementia
Frontotemporal dementia tends to affect individuals at younger ages than AD or vascular dementia, with approximately 75% of cases occurring in individuals under the age of 65.³⁴ As described previously, vascular dementia and advanced AD can cause atrophy throughout the brain. In contrast, FTD affects primarily the frontal lobes and the anterior portions of the temporal lobes of the cerebral cortex.¹⁹ The frontal cortex is important in regulating normal social behavior, as well as in the ability to coordinate and carry out complex tasks. Clinical signs and symptoms of FTD include a relatively rapid decline in language ability, and problems carrying out complex tasks or managing normal day-to-day activities. Some patients exhibit rapid and dramatic changes in personality, including language or behavior that is rude, insensitive, or sexually inappropriate.³⁰

Structural neuroimaging, usually with MRI, is an important part of the diagnosis of FTD.²⁵ Atrophy of the frontal lobes, hippocampus, and amygdala are common findings.  Coronal MRI is especially important to visualize characteristic atrophy patterns in some patients with FTD. Other characteristics that are common with structural neuroimaging include increased signal intensity in subcortical white matter on T2 and proton-density weighted images; anterior or diffuse degeneration of the corpus callosum on conventional or quantitative MRI; and reduced frontal lobe or hippocampal volumes.²⁵ In general, there are 3 subtypes of FTD, and they vary somewhat in the distribution of abnormal findings on MRI^19,35:

• Behavioral variant of FTD (bvFTD): presents with early behavioral abnormalities; atrophy is greatest in the frontal lobes, and may also occur in the temporal lobes.
• Semantic dementia (SD): presents with early language deficits, especially difficulty with remembering words; atrophy is especially pronounced in the anterior portion of the temporal lobes, is often asymmetric, and involves especially the left side.
• Progressive nonfluent aphasia (PNFA): memory for individual words is often relatively intact, but the patient exhibits slowed speech or difficulty with articulating or pronouncing words, often accompanied by grammatical errors; atrophy is generally limited to the cerebral cortex on the left side.

Representative MRI findings for these 3 subtypes are shown in Figure 3.²⁵

In some cases, it may be difficult to distinguish AD from FTD using a CT or MRI scan. For example, some patients with AD have a variant of the disease that is characterized by marked atrophy of the frontal lobes, and these patients are sometimes mistakenly diagnosed with FTD on the basis of MRI or CT imaging. Functional imaging techniques such as SPECT and PET scanning have increasingly been used to distinguish FTD from AD with marked frontal lobe involvement. These techniques have been used to show that patients with FTD often exhibit more marked disturbance of glucose uptake or brain perfusion of the frontal portions of the brain than in patients with AD, and that these deficits are more likely to occur unevenly on the 2 sides of the brain.¹⁹ The use of PET imaging has been shown to increase the diagnostic accuracy of FTD beyond clinical assessment alone, and specific metabolic patterns have been noted with the 3 clinical presentations of FTD: frontal hypometabolism in bvFTD, temporal hypometabolism with SD, and hypometabolism of the left perisylvan area with PNFA.²⁵ SPECT imaging is also sometimes used clinically or for research purposes to distinguish AD from FTD.

Emerging Technologies for Imaging Dementia
Several other imaging techniques are used less often in the clinical setting for the routine evaluation of patients with dementia, but may be used under special circumstances or in research studies. Each technique provides information about a different type of physiological process within the brain. It may be possible to combine information from different methods to create a more detailed and accurate depiction of brain changes in different types of dementia. An important goal of this research is to identify individuals who are at high risk of brain tissue loss or other disease processes, and to intervene early to prevent the eventual development of dementia.⁷

Functional MRI (fMRI) measures changes in magnetic resonance signal intensity within the brain while the subject performs a particular mental task, such as reading a list of words or answering questions on a memory test. These changes in the MRI signal provide an indirect measure of the level of activity in different brain regions, and they have also been used to demonstrate that the connections between different parts of the brain can become damaged in patients with dementia.³⁶ Although fMRI is primarily an experimental technique that is not used in routine clinical practice, some research studies have found that fMRI is able to distinguish individuals with AD or MCI from healthy control subjects.³⁷

Diffusion tensor imaging (DTI) is a technique that examines the extent to which water molecules in a region of brain tissue tend to move together in the same direction. White-matter pathways within the brain are made up of bundles of nerve fibers that tend to lie parallel to one another. In healthy white-matter fiber tracts, water molecules diffuse along these nerve fibers, and therefore move in the same direction. This tendency to move together in one direction is called anisotropy. In contrast, water molecules in injured white-matter tracts are more likely to move in a random, spherical distribution. Studies of patients with dementia have identified changes in water anisotropy in the brains of patients with AD, have used DTI to distinguish AD from vascular dementia or other types of dementia, and have identified early changes in anisotropy in patients who have certain genetic risk factors for AD but who do not yet have symptoms of dementia.⁷ DTI has also been used to identify subtle white-matter lesions in patients with dementia in areas of white matter that appear normal using other imaging technologies.³⁸

Magnetic resonance spectroscopy (MRS) uses unique magnetic resonance signals that are produced by protons to identify the presence of a variety of molecules that are important in the structure and function of the CNS. For example, the amino acid N-acetylaspartate (NAA) is a specific marker for nerve cells, and is decreased across much of the brain in patients with early AD.³⁹ Determination of NAA levels using MRS has also been used to predict which patients with MCI are most likely to progress to dementia,⁴⁰ and to monitor changes in brain tissue in patients with AD who are being treated with medications for dementia.⁹

Dementia and the Radiologic Technologist
In the United States and other industrialized nations, the average age of the population has increased over the last several decades, and this trend is expected to continue in the future. As the number of people with AD and other types of dementia increases, radiologic technologists will increasingly be called upon to perform neuroimaging procedures in elderly patients with significant cognitive impairments. Older patients are also more likely to have several other age-related medical problems that make the radiology session more difficult, such as hearing or vision loss, arthritis, and problems balancing.¹² Although the use of imaging technologies in this population may be challenging, a correct diagnosis is essential in ensuring that patients receive appropriate therapy to prevent further loss of mental functioning. Neuroimaging provides a set of tools to diagnose different types of dementia with a high degree of accuracy, and it has become an essential part of the routine workup for patients with cognitive impairments. Recommendations to safely examine older patients include¹²:

• Do not leave a patient who appears confused or who shows other signs of dementia unattended
• Support the patient when moving to or from the examination table
• Accompany the patient to and from the restroom, dressing room, or discharge area
• Ask a family member or other familiar person to help the patient in the examination room

Suggestions for communicating with a patient or other person with dementia include⁴¹:

• Avoid distractions and noise when talking with the patient
• Keep communication simple: use plain words, short sentences, and avoid complex questions or instructions
• Break complicated tasks down into single steps

Conclusions
Dementia is common among patients with many different types of brain diseases, including AD, cerebrovascular disease, DLB, and FTD. Patients with dementia often present unique challenges in the imaging facility due to their age, impairments of memory and language, and the likelihood of comorbid conditions. However, imaging has become a standard part of the diagnostic process for individuals with cognitive impairments, and is often essential in selecting an appropriate treatment course. Structural imaging techniques such as MRI or CT have long been used to identify potentially reversible causes of cognitive impairment, such as a brain tumor or bleeding. Functional imaging techniques were traditionally used primarily in the research setting, but recent advances have stimulated the use of PET, SPECT, and other functional imaging techniques in the routine assessment of patients with dementia. Newer technologies are continuing to expand the possibilities for neuroimaging in dementia, including highly specific molecular imaging probes for AD-related proteins, and new techniques to visualize very early changes in white matter. Effective communication between the patient and the radiologic technologist is an important step in ensuring that high-quality neuroimages are obtained as safely and as efficiently as possible. 

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