Functional neuroimaging for primary degenerative dementia or mild cognitive impairment

Policy context

Functional neuroimaging involves the injection into the blood of radiolabeled ligands. The radiolabeled ligands flow in the blood supply to the brain and are then detected by a scanner allowing visualization of the blood supply within the brain. There are significant questions related to the use of functional neuroimaging for the diagnosis of primary neurodegenerative dementia and mild cognitive impairment, specifically, there are medium concerns regarding safety, efficacy, and cost.

Status: Decision completed

Primary Criteria Ranking

  • Safety = Medium
  • Efficacy = Medium
  • Cost = Medium

Assessment timeline

  • Draft key questions published: May 16, 2014
  • Public comment period: May 16 to June 2, 2014
  • Final key questions published:  June 6, 2014
  • Draft report published: October 20, 2014 
  • Public comment period: October 20 to November 20, 2014
  • Final report published: December 15, 2014
  • HTCC public meeting: January 16, 2015


Dementia is a broad term that describes cognitive and/or behavioral (neuropsychiatric) symptoms that affect a patient's ability to function at work or in daily activities. The patient's condition represents a decline from previous abilities and is not attributable to delirium or a major psychiatric disorder, and represents cognitive and behavioral impairment (i.e., impairment of at least two of the following: memory, reasoning/judgment, visuospatial abilities, language functions, personality/behavior). Dementia ranges in severity from mild to severe. Cognitive impairment can be detected by a combination of history-taking and cognitive assessment using mental status or neuropsychological testing. The condition of mild cognitive impairment (MCI) is primarily distinguished from that of dementia when the patient maintains the ability to function at work or in usual daily activities.

Dementia can be caused by a number of conditions and diseases. The most common cause of dementia is Alzheimer's Disease (AD), which is most prevalent in older people. Other causes of dementia include vascular dementia (VaD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Parkinson's Disease. Mixed dementia can also occur, in which patients have a combination of two or more types of dementia. Some forms of dementia can be reversed or treated with appropriate treatment including normal pressure hydrocephalus, subdural hematoma, tumor, thyroid problems, and vitamin B deficiency.

Diagnosis of dementia

Patients presenting with symptoms or complaints suggestive of dementia undergo an initial evaluation consisting of a thorough history, detailed cognitive testing, and neurological examination. Most clinical practice guidelines recommend that patients who meet clinical criteria for dementia undergo at least one structural neuroimaging procedure (computed tomography (CT) or magnetic resonance imaging (MRI) scan) and laboratory testing to exclude reversible causes of dementia such as subdural hematoma or tumor. Structural neuroimaging may also aid in the diagnosis of dementia subtype based on patterns of atrophy. After this initial comprehensive work-up, a specific diagnosis is generally able to be made. However, in some patients the diagnosis remains unclear and additional testing with functional imaging may be conducted in order to make an accurate diagnosis.

Technology of interest

Functional neuroimaging is an add-on diagnostic test. Typically, it is only done in addition to structural neuroimaging to confirm a diagnosis. In contrast to structural imaging, functional neuroimaging can provide specific information regarding specific brain functions. Functional neuroimaging involves the injection of radiolabeled ligands, which are then detected by the scanner. Types of functional neuroimaging include single-photon emission computed tomography (SPECT), positron emission tomography (PET), and functional MRI (fMRI). SPECT can measure dopaminergic nigrostriatal denervation, which occurs in patients with DLB, using the radiolabeled dopamine transporter ligand 123I-FP-CIT (2β-carbometoxy-3β-(4-iodophenyl)-B- (3-fluoropropyl) nortropane). SPECT can also assess cerebral blood flow using 99mTC-HMPAO (hexamethylpropylene amine oxime). Because cerebral blood flow correlates with brain metabolism, the images provide information regarding which regions of the brain are affected, which in turn aids with differential diagnosis. FDG (fludeoxyglucose) PET also provides information regarding brain metabolism by measuring glucose uptake. PET can also be used to detect presence of β-amyloid protein, which accumulates in Alzheimer's Disease brains, using 18F-florbetaben or PiB (Pittsburgh compound B), both of which detect β-amyloid protein.

Functional neuroimaging has the capability of aiding in the differential diagnosis of AD, DLB, and FTD disorders (including primary progressive aphasia (PPA). Functional neuroimaging is not typically used in the diagnosis of vascular dementia due to the high resolution and ability of MRI to show subtle vascular changes in white matter, although it could be used to detect AD or FTD in a patient with dementia and vascular disease for whom the diagnosis was not clear. While functional imaging is typically not used to diagnose mild cognitive impairment, preclinical diagnosis of AD is possible using amyloid PET imaging and would give patients a diagnosis and help them plan for the future. It is anticipated that if effective therapies for dementia, including AD, are discovered in the future, they would likely be most effective in the earlier stages of the disease. Should this occur, the availability of functional imaging for those with mild cognitive impairment would be very important.