Guidelines for Imaging Evaluation of Dementia

EFNS task force: the use of neuroimaging in the diagnosis of dementia from the National Guideline Clearinghouse [PubMed Abstract] [Full Text HTML] [Full Text PDF] [Cited by other articles] Eur J Neurol. 2012 Dec;19(12):e131-40, 1487-501. doi: 10.1111/j.1468-1331.2012.03859.x. Epub 2012 Aug 20.

All of the following is from the excellent article above:

Recommendations for structural MRI [For the basis of these recommendations, Structural MRI Findings, see pp. 1489 – 1493]

  1. Structural imaging should be carried out at least once in the diagnostic work-up of patients with cognitive impairment and serves at least three purposes: to exclude other potentially treatable diseases, to recognize vascular lesions and to identify specific findings to help distinguish different forms of neurodegenerative types of dementia (good practice point).
  2. MRI is currently the imaging modality of choice for assessing subjects with suspected dementia. However, where MRI is not available or contraindicated, CT scans can usefully exclude major space occupying lesions, large infarcts and hydrocephalus (good practice point). Multi-detector row CT is the best alternative for patients who cannot undergo MRI (good practice point).
  3. A standard MRI protocol should include a high-resolution structural volumetric T1-weighted scan, transverse T2-weighted and FLAIR sequences and transverse T2*-gradient echo sequence (good practice point). Routine contrast administration is not indicated (good practice point). DWI can be useful to identify recent infarcts, as well as cortical and/or basal ganglia changes in CJD patients (good practice point).
  4. It is particularly difficult to attribute clinical significance to evidence of cerebrovascular disease in patients with cognitive impairment. Vascular changes on CT or MRI do not preclude a diagnosis of degenerative dementia, especially in older age. A diagnosis of vascular dementia should only be made where the vascular lesion(s) can explain the cognitive deficit (class II, level A). The ‘mixed dementia’ label should be reserved for those cases in which both clinical features and diagnostic markers point to a mixed aetiology (good practice point).
  5. T1-weighted images should be carefully evaluated to assess specific patterns of focal atrophy, especially in the MTL, biparietal regions and posterior cingulate cortex (as seen in AD), temporal pole and/or frontal lobes (as seen in FTD), parietal/occipital lobe (as seen in PCA), putamen, and midbrain and frontal lobe (as seen in PSP) (good practice point).
  6. Coronal T1-weighted sequence can be used to assess MTL atrophy to support a clinical diagnosis of AD compared with cognitively normal subjects (class II, level A). Prediction of subsequent AD in individuals with amnestic MCI can also be obtained with MRI volumetric measures of the MTL (class II, level A). However, at present, accepted standards for quantitative MTL volume measurement are lacking. Therefore, quantification must rely on local specific standards (good practice point).
  7. Combining MTL measures with other potentially informative markers, such as posterior cingulate cortex and precuneus volumetric measures, are likely to improve diagnostic confidence in AD patients (class II, level B), mainly in younger cases.
  8. In cases of atypical AD presentations, the involvement of the MTL is reported less consistently than that of lateral temporal and medial parietal regions (class III, level B).
  9. No established structural MRI pattern is characteristic for DLB (class II, level A). However, the absence of MTL atrophy on CT or MRI may be suggestive of a diagnosis of DLB compared with AD (class II, level A).
  10. The pattern of atrophy is more useful than atrophy of single regions in the differential diagnosis of FTD compared with AD: knife-edge, severe frontotemporal atrophy combined with dilatation of frontal horn, and an anterior greater than posterior gradient is suggestive of a diagnosis of FTD (class II, level A).
  11. A normal structural MRI scan should prompt the clinician to reconsider a diagnosis of bvFTD, if clinically severe, and semantic variant PPA (good practice point).
  12. Presence of knife-edge frontal and/or temporal lobe atrophy in patients with PPA is predictive of FTLD pathology, whilst the presence of temporoparietal atrophy is highly associated with AD (class III, level C)

Recommendations for functional imaging [For the basis of these recommendations, Functional MRI Findings, see pp. 1494 – 1497]

  1. Although typical cases of dementia may not benefit from routine SPECT or PET imaging, these tools are recommended in those cases where diagnosis remains in doubt after clinical and structural MRI work-up and in particular clinical settings (class II, level A).
  2. Functional imaging can be of value to diagnose (or exclude) a neurodegenerative dementia in those subjects with cognitive impairment presenting with severe psychiatric disturbances (including depression and agitation) and in cases where proper cognitive testing is difficult, that is, with no language in common with the clinician (good practice point).
  3. Normal FDG PET scan findings, in the presence of the suspicion of dementia, make a neurodegenerative diagnosis less likely (class II, level A).
  4. The overall regional pattern of metabolic impairment of the posterior cingulate/precuneus and lateral temporoparietal cortices, more accentuated than frontal cortex deficits, together with the relative preservation of the primary sensorimotor and visual cortices, basal ganglia and cerebellum defines the distinct metabolic phenotype of AD (class II, level A).
  5. AD-like metabolic patterns in patients with MCI are predictive of conversion to AD within several years (class II, level A).
  6. Occipital hypometabolism, particularly in the primary visual cortex, may be more common in DLB than AD on a group basis (class II, level B). However, on individual scans, the appearances of DLB and AD can be identical. Moreover, occipital hypometabolism is not a specific marker for DLB and can be associated with AD (good practice point).
  7. Although an overlap of functional abnormalities between FTD and AD has been shown to occur, the presence of posterior temporal and parietal brain hypoperfusion or hypometabolism is predictive of a pathological diagnosis of AD, whereas a disproportionate reduction in frontal perfusion/metabolism is more common in FTD cases (class II, level A).
  8. In PPA patients, bilateral posterior temporoparietal hypometabolism (PET) or hypoperfusion (SPECT) is predictive of AD pathology; normal bilateral posterior temporoparietal function is specific for FTLD (class III, level C).
  9. Dopaminergic SPECT is useful to distinguish DLB from AD (class I, level A), especially when there are no clear extrapyramidal symptoms and signs. However, a negative 123I-FP-CIT scan does not necessarily exclude a diagnosis of probable DLB, as around 20% of individuals with probable DLB appear to have normal scans (class I, level A).
  10. Dopaminergic SPECT can be useful in differentiating DLB from long-term psychiatric patients on neuroleptic drugs, whose parkinsonism may be drug-induced (good practice point).

ACR Appropriateness Criteria® dementia and movement disorders 2015 from National Guideline Clearinghouse. [PubMed Abstract] [Full Text PDFJ Am Coll Radiol. 2015 Jan;12(1):19-28. doi: 10.1016/j.jacr.2014.09.025.

All of the following is from the ACR Appropriateness Criteria above [and the article is an excellent brief (17 pages) summary]:

Summary of Literature Review


Degenerative disease of the central nervous system (CNS) is a growing public health concern. The prevalence of dementia, one of the leading degenerative conditions, is expected to quadruple by 2050 [1]. Other degenerative diseases may affect the extrapyramidal system and the motor system.

Dementia is characterized by a significant loss of function in multiple cognitive domains without affecting the general level of arousal. Several forms are now recognized, including Alzheimer disease (AD), frontotemporal dementia (FTD), Lewy body disease, and the vascular dementias. Although the causes of most dementias remain elusive, genetic research has opened many frontiers in understanding the pathophysiology of heretofore enigmas such as AD [1,2]. Additionally, infectious, vascular, and toxic etiologies have become increasingly more appreciated as causes of cognitive decline. Trauma with brain injury may also be associated with premature dementia.

The extrapyramidal centers are large subcortical nuclear structures from which output systems emerge at several points. Since mediation and control of the corticospinal tract are the most prominent functions of these output systems, lesions of the extrapyramidal nuclei typically result in motor dysfunction and movement disorders of various types. Examples of extrapyramidal diseases include Huntington disease (HD), neurodegeneration with brain iron accumulation (NBIA), and Parkinsonism and its variants.

Finally, motor neuron diseases are a heterogeneous group of syndromes in which the upper and/or lower motor neurons degenerate. Amyotrophic lateral sclerosis (ALS) is the most frequent type of motor neuron disease, although an increasing number of variants are being recognized.

Overview of Imaging Modalities

Neuroimaging has played an increasing role in the understanding, diagnosis, and management of degenerative diseases of the CNS by supplementing and complementing current clinical tests. Neuroimaging may be divided into structural neuroimaging, which evaluates anatomic changes that occur in neurodegenerative conditions, and functional neuroimaging, which evaluates CNS activities such as blood flow and metabolism in neurodegenerative conditions. For example, structural neuroimaging with computed tomography (CT) and magnetic resonance imaging (MRI) has defined patterns and rates of brain volume loss in AD [3-5]. Moreover, structural neuroimaging may exclude treatable conditions that may present with dementia-like symptoms. Functional neuroimaging with MRI (fMRI), single photon emission CT (SPECT), and positron emission tomography (PET) have greatly assisted in the understanding of blood flow, metabolism, and amyloid deposition in demented patients [6]. Application of MR spectroscopy (MRS) has also yielded novel information about degenerative processes.

Despite tremendous insights into the pathophysiology of neurodegenerative processes provided by advanced imaging, application of these techniques in everyday practice does have certain limitations in patients with neurodegenerative disorders. First of all, frequently observed imaging findings of white-matter disease and general atrophy are nonspecific and may not necessarily refine the differential diagnosis of dementia or neurodegeneration [7]. Although many of the newer imaging techniques have penetrated the American markets, some of the advanced modalities are still not widely available in some communities. Additionally, many of these patients are frail and confused and may not tolerate long scanning times. Also, older patients may have significant comorbidities, such as cardiac pacemakers or renal insufficiency, which may limit the choice of available modalities and administration of intravenous contrast agents. Moreover, the cost of imaging must be weighed against its potential benefits, especially because most neurodegenerative diseases are considered incurable, have only limited available palliative medical therapies, and have no current options to slow disease progression. In an older study, Simon and Lubin [8] determined that CT might detect from 1,400 to 15,000 potentially treatable lesions per 100,000 demented patients scanned at an estimated cost of $49 million in 1985, a cost now certainly much higher. The addition of MRI might allow the identification of 70 to 150 additional treatable cases but would almost double the cost according to these authors. Also, treating selected lesions detected on these scans would not necessarily guarantee return to prepresentation functional status, assuming patients were even appropriate candidates for the proposed treatment [8]. Finally, many of these elderly patients may have more than one condition contributing to the clinical manifestation of neurodegeneration.

Brief discussions of the rationale for the various imaging modalities by Variant is on pp. 8 thru 14.

The Variants considered are:

Variant 1: Probable Alzheimer’s disease.
Variant 2: Possible Alzheimer’s disease.                                                                                      Variant 3: Suspected frontotemporal dementia.                                                                  Variant 4: Suspected dementia with Lewy bodies.                                                              Variant 5: Suspected vascular dementia.                                                                              Variant 6: Suspected prion disease (Creutzfeld-Jakob, iatrogenic, or variant).            Variant 7: Suspected normal pressure hydrocephalus.                                                         Variant 8: Suspected Huntington disease.                                                                            Variant 9: Clinical features suggestive of neurodegeneration with brain iron      accumulation.                                                                                                                              Variant 10: Parkinson disease. Typical clinical features. Responsive to levodopa.      Variant 11: Parkinsonian syndrome. Atypical clinical features. Not responsive to  levodopa.                                                                                                                                      Variant 12: Motor neuron disease.

Summary of Recommendations
-The primary function of anatomic neuroimaging studies in evaluating the patient with dementia or movement
disorder is to rule out structural causes that may be reversible.
-Lack of sensitivity and specificity of many neuroimaging techniques applied to a variety of neurodegenerative disorders has limited the role of neuroimaging in differentiating types of neurodegenerative disorders encountered in everyday practice.
– Neuroimaging is a valuable research tool and has provided insight into the structure and function of the brain in patients with neurodegenerative disorders.
– Advanced imaging techniques such as fMRI and MRS hold exciting investigative potential for better understanding of neurodegenerative disorders, but they are not considered routine clinical practice at this time.

Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association from the National Guideline Clearing House. [PubMed Abstract] [Full Text HTML] [Full Text PDF] J Nucl Med. 2013 Mar;54(3):476-90. doi: 10.2967/jnumed.113.120618. Epub 2013 Jan 28.



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