Positron Emission Tomography Scans Obtained for the Evaluation of Cognitive Dysfunction

doi:10.1053/j.semnuclmed.2008.02.006

Seminars in Nuclear Medicine

Volume 38, Issue 4, July 2008, Pages 251-261

https://doi.org/10.1053/j.semnuclmed.2008.02.006 Get rights and content

The degree of intactness of human cognitive functioning for a given individual spans a wide spectrum, ranging from normal to severely demented. The differential diagnosis for the causes of impairment along that spectrum is also wide, and often difficult to distinguish clinically, which has led to an increasing role for neuroimaging tools in that evaluation. The most frequent causes of dementia are neurodegenerative disorders, Alzheimer's disease being the most prevalent among them, and they produce significant alterations in brain metabolism, with devastating neuropathologic, clinical, social, and economic consequences. These alterations are detectable through positron emission tomography (PET), even in their earliest stages. The most commonly performed PET studies of the brain are performed with ¹⁸F-fluorodeoxyglucose as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic utility for clinicians evaluating patients with cognitive impairment and in distinguishing among primary neurodegenerative disorders and other etiologies contributing to cognitive decline. In addition to focusing on the effects on cerebral metabolism examined with ¹⁸F-fluorodeoxyglucose PET, some other changes occurring in the brains of cognitively impaired patients assessable with other radiotracers will be considered. As preventive and disease-modifying treatments are developed, early detection of accurately diagnosed disease processes facilitated by the use of PET has the potential to substantially impact on the enormous human toll exacted by these diseases.

Section snippets

Limitations of Conventional Clinical Evaluation

A definite diagnosis of AD can be made only by histopathologic examination of brain tissue.³ The identification and differential diagnosis of AD is especially challenging in its early stages, partly because of the difficulty in distinguishing it from the mild decline in memory that can occur with normal aging and from mild cognitive manifestations of other neuropsychiatric conditions, such as depression, as well as other causes of dementia. False-positive and false-negative diagnoses with

FDG-PET Studies of Normal Adult Brain and Healthy Aging

Clinical PET studies of the brain are performed most commonly with the use of ¹⁸F-fluorodeoxyglucose (FDG). The resulting scans are typically interpreted qualitatively, by visual analysis, although quantitative software tools are becoming increasingly used as adjuncts to interpretation. In either case, the relative distribution of FDG throughout the patient's brain is examined, and compared with the distribution expected for a normal subject.

When quantification is performed, it may be expressed

From Normal to Mild Decline in Cognition to Dementia

As minimal gradual changes are expected with healthy aging, with respect to both cognitive abilities and cerebral metabolism, evaluating patients in the earliest stages of potentially pathologic change requires initiating that process at the time that decline first becomes evident. The decline may be noted by a physician with whom the patient has an ongoing relationship, by a family member or other close contact of the patient, or by the history provided by a patient who is deemed to be

Diagnosis of Dementing Illnesses

A wide variety of neurodegenerative diseases has been demonstrated to produce significant alterations in brain function detectable with PET. Distinguishing these alterations with PET has served as a subject of considerable investigation for three decades,69, 70, 71, 72 and continues to be actively studied and extensively reviewed.44, 73, 74, 75 Many thousands of patients with clinically diagnosed—and, in some cases, histopathologically confirmed—causes of dementia from many independent

Other Tracers

Although clinical applications of PET in the evaluation of patients with conditions leading to cognitive impairment and dementia have largely focused on FDG, many other tracers have been used in this context. Although a detailed consideration of those tracers is beyond the scope of the present review, a few such examples will be mentioned here. To begin, the use of PET to study cerebrovascular disease, as with AD, also enjoys a long history, extending back to the time of the earliest dementia

Future Directions

It is evident that the biologic changes that occur with AD take place decades before the onset of clinical symptoms. The use of more powerful diagnostic approaches allows the earlier detection of initial changes in a target population long before a diagnosis of AD can be made. Currently, the availability of tools for identifying the early changes of AD is outpacing the available therapeutic options. With advances in potential disease-modifying treatments, the benefits of early detection will

Acknowledgment

We are indebted to Erin Siu and Vicky Lau for their assistance with manuscript preparation.

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Positron Emission Tomography Scans Obtained for the Evaluation of Cognitive Dysfunction

Section snippets

Limitations of Conventional Clinical Evaluation

FDG-PET Studies of Normal Adult Brain and Healthy Aging

From Normal to Mild Decline in Cognition to Dementia

Diagnosis of Dementing Illnesses

Other Tracers

Future Directions

Acknowledgment

Lancet

Clin Ther

Biol Psychiatry

Eur Neuropsychopharmacol

Mol Genet Metab

Lancet Neurol &

Radiol Clin N Am

Clin Positron Imaging

Am J Geriatr Psychiatry

Alzheimer's Association: Alzheimer's Disease Facts and Figures

Cognitive measures predict pathologic Alzheimer disease

Arch Neurol

Documentation and evaluation of cognitive impairment in elderly primary care patients

Ann Intern Med

Diagnostic errors in the evaluation of behavioral disorders

JAMA

Clinico-neuropathological correlation of AD in a community-based case series

J Am Geriatr Soc

AD: The problem of incorrect clinical diagnosis

J Geriatr Psychiatry Neurol

Practice parameter: diagnosis of dementia (an evidence-based review)Report of the Quality Standards Subcommittee of the American Academy of Neurology

Neurology

Rivastigmine for ADCochrane Database Systemic Review

The effects of donepezil in AD: Results from a multinational trial

Dementia

A randomized trial evaluating the efficacy and safety of ENA 713 rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe AD

Int J Geriatr Psychopharmacol

A 30-week randomized controlled trial of high-dose tacrine in patients with ADThe Tacrine Study Group

JAMA

Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extensionThe Galantamine USA-1 Study Group

Neurology

The efficacy and safety of donepezil in patients with AD: Results of a US multicentre, randomized, double-blind, placebo-controlled trial

Dementia

Efficacy and safety of Rivastigmine in patients with AD: International randomized controlled trial

BMJ

Long-term tacrine (Cognex) treatment effects on nursing home placement and mortalityThe Tacrine Study Group

Neurology

A controlled trial of selegiline, alpha-tocopherol, or both as treatment for AD

N Engl J Med

Metrifonate benefits cognitive, behavioral, and global function in patients with AD

Neurology

A 5-month, randomized, placebo-conrtrolled trial of galantamine in AD

Neurology

Effects of donepezil on emotional/behavioral symptoms in AD patients

J Clin Psychiatry

Dementia: Causes, evaluation, and management

Hosp Pract (Off Ed)

Two-year treatment of AD with eptastigmine

Dement Geriatr Cogn Disord

Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer diseaseDonepezil Study Group

Arch Neurol

Are memory complaints predictive for dementia?A review of clinical and population-based studies

Int J Geriatr Psychiatry

Memory complaints in a community sample aged 60-64 years: associations with cognitive functioning, psychiatric symptoms, medical conditions, APOE genotype, hippocampus and amygdala volumes, and white-matter hyperintensities

Psychol Med

The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: Theory, procedure and normal values in the conscious and anesthesized albino rat

J Neurochem

Noninvasive determination of local cerebral metabolic rate of glucose in man

Am J Physiol

Effects of stroke on local cerebral metabolism and perfusion: mapping local metabolism and perfusion in normal and ischemic brain by emission computed tomography of 18FDG and 13NH3

Ann Neurol

Tomographic mapping of human cerebral metabolism: normal unstimulated state

Neurology

Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxyglucose: Validation of method

Ann Neurol

The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man

Circ Res

The metabolic topography of normal aging

J Cereb Blood Flow Metab

Evaluation of standardized uptake value to assess cerebral glucose metabolism

Clin Nucl Med

The [¹⁴C]deoxyglucose method for the measurement of local cerebral glucose utilization: Theory, procedure and normal values in the conscious and anesthesized albino rat

Effects of stroke on local cerebral metabolism and perfusion: mapping local metabolism and perfusion in normal and ischemic brain by emission computed tomography of ¹⁸FDG and ¹³NH₃

The [¹⁸F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man