Key Results

  1. 1.

    The assessment of dementia is based on clinical, radiological, nuclear and lab evaluation.

  2. 2.

    Brain atrophy, white matter lesions, microhemorrhages, and vascular diseases should be radiologically evaluated.

  3. 3.

    Radiological assessment should be based on visual assessment, scoring, and volumetry.

  4. 4.

    The disease-oriented structured radiology report increases its clinical value.

  5. 5.

    Multidisciplinary teamwork increases diagnostic accuracy.

Background

Dementias are taking up more space in everyday clinical and radiological scenarios, considering that the worldwide population is aging [78] and that brain imaging plays a key role in the assessment of cognitive impairment [8]. In addition, the scientific community is increasingly focused on the debate over the use of AI [51], FDA- and EC-approved automated segmentation software [73], and the optimal use of neuroimaging in new drug trials [68].” A recent survey, carried out in Europe among academic and non-academic institutions [74], disclosed that the current practice in dementia imaging presents some homogeneity (mainly in imaging acquisition and image interpretation) but also differences in training and reporting, in using advanced imaging techniques and volumetric measures, as well as in communication between clinicians and radiologists. This work stems from the need of different Italian scientific societies to standardize and optimize the radiological approach for the assessment and follow-up of the aging brain and cognitive disorders.

We aim to fill this gap of variability and uncertainty, providing a practical approach in evaluating, interpreting, and monitoring the aging brain and main cognitive disorders.

Methods

The promoters of the initiative (FBP and SB) representatives of the Neuroradiological Section of the Italian Society of Radiology (SIRM), with the clinical support of EC and GBF, created a core panel with experts in dementia and cognitive disorders representatives of the Italian Association of Diagnostic and Interventional Neuroradiology (AINR). The purpose of their work is to submit a preliminary consensus draft to the representatives of SIGG (Italian Society of Geriatrics and Gerontology, Società Italiana di Geriatria e Gerontologia) and AIP (Italian Association of Psychogeriatrics, Associazione Italiana di Psicogeriatria) for their revision and final approval.

The main research questions were:

  • Define the key concepts (A) of what the radiologist needs to know: main clinical features (definition of brain aging, cognitive syndromes, and primary and secondary dementias) and imaging findings.

  • Frame the MRI radiological approach for the assessment and follow-up of the aging brain and cognitive disorders—MRI protocol (B), imaging evaluation and interpretation (C), and reporting (D) for clinical use

  • Identify the main factors that will influence clinical and radiological practice in this population in the near future (E)

  • The consensus between experts was reached using a similar approach to the previously published paper (Pizzini FB et. Insights Imaging) and consisted in:

    • A critical review of previous literature by European/American task forces and scientific societies related to A–D

    • Circulation and discussion of the draft based on this review among the core panel and then between the experts in more rounds

    • Changes of the original draft till the group converged towards an agreement on all the points A–E

Literature review

Literature review was performed through the PubMed database and on the web through Google and Google Scholar platforms, as well as specialized websites (Radiopaedia.org and radiologyassistant.nl/neuroradiology) and textbooks. The standardized strings used to search the database for literature were structured by combining the keywords (1) disease of interest, (2) biomarker (3) guidelines/recommendations/evaluation. As shown in the flowchart (Fig. 1), only original texts (abstract and full text) published in English were considered, without filtering for article type and publication date. Articles were selected after a review of the titles and abstracts of the first fifteen “best matches” to determine relevance and affinity to the research purpose. When it was useful, consultation was extended to the bibliographic references of the selected articles. Finally, in our bibliography, articles range from 1988 to 2022, with a predominance of the last decade.

Fig. 1
figure 1

Flow-chart of bibliographic research and related tables

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Results

(A) Introduction to aging, cognitive impairment, and dementia

The following boxes represent consensus findings related to the key concepts (Box 1) and clinical features and imaging findings (Boxes 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11) of the major primary and secondary dementias.

Box 1 Glossary and definitions
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Box 2 Late-onset Alzheimer Disease (Lo-AD)
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Box 3 Early-onset Alzheimer Disease (Eo-AD: “not just an AD at a younger age”)
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Box 4 Vascular dementia (VaD)—Vascular cognitive impairment (VCI) “not strictly a neurodegenerative dementia ┼”
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Box 5 Dementia(s) with Lewy Bodies—DLB (Lewy Body Dementias – LBDs)
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Box 6 Frontotemporal dementias (FTDs)
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Box 7 Corticobasal degeneration (CBD)
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Box 8 Sporadic Creutzfeldt-Jakob disease (sCJD) ┼
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Box 9 Cerebral amyloid angiopathy (CAA)
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Box 10 Chronic central nervous system complications of alcohol (ab)use [overview of main conditions]
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Box 11 Idiopathic Normal Pressure Hydrocephalus—iNPH ┼
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(B) MRI protocol (acquisition)

  1. 1.

    Field of the MRI suite (1.5; 3T). The choice of field strength does not affect the evaluation of atrophy or white matter load (WML), but it can affect the detection rate of microbleeds [46].

  2. 2.

    Standard protocol (core sequences and parameters). They have been found to have a major impact on image resolution [15] thus on the detection rate of atrophy, white matter changes, and microbleeds (e.g. in GRE detection of 33% of the microbleeds identified by thin-section SW [46, 65]) (Table 1).

  3. 3.

    Optional additional sequences (i.e. functional MRI, microstructural DWI, spectroscopy, Magnetization Transfer Imaging) are useful at the group level [25] when comparing a specific disease with healthy subjects or other clinically overlapping diseases, Level 1 of a five-level scale of Imaging biomarkers [18, 77]. While ASL (Arterial Spin Labeling) is useful at the individual level because it reaches a sensitivity and specificity > 80% for the clinical diagnosis of a given patient (Level 2 of the same scale). None of these sequences can be considered effective for early clinical diagnosis (Level 3) or could be used as surrogate criteria for pathological diagnosis (Level 4) or provide a direct measure of the underlying neuropathological changes (Level 5).

  4. 4.

    Contrast-enhanced MR: Contrast Media injection not indicated in aging and cognitive impairment (except for CAA-ri, see Box 8. CAA).

Table 1 MRI protocol
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(C) Evaluation and interpretation

  1. 1.

    Visual (qualitative) assessment

Table 2.

  1. 2.

    Visual rating scales

  2. (a)

    ATROPHY (see Tables 3 and 4; Figs. 2 and 3, and 4) should be evaluated in multiple planes on T1 (or FLAIR, but not T2), comparing the most preserved sulci/gyri (usually the occipital ones) to the most affected ones, symmetrically, using these scales:

Table 2 Qualitative visual assessment
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Table 3 GCA-Koedam scale/score. GCA/Koedam score > 2 can be considered pathological
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Table 4 Visual rating scale MTA-Scheltens
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Fig. 2
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Axial T1 weighted images showing with increasing GCA score values from left (GCA = 0) to right (GCA = 3). The score reported is referred to the most affected brain area

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Fig. 3
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Axial T1 weighted images showing increasing parietal atrophy from left (Koedam = 0) to right (Koedam = 3)

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Fig. 4
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T1 weighted coronal images placed symmetrically and perpendicularly to the long axis of the hippocampi. Different grades of medial temporal lobe atrophy are shown, and they are rated both on the left and on the right hippocampi

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Global cerebral Atrophy (GCA) [49], Koedam for posterior lobes—which are most affected in atypical AD [34], MTA-Scheltens for medial temporal lobe [60].

  1. (b)

    WHITE MATTER CHANGES (WMC) (see Tables 5 and 6; Fig. 5) should be evaluated in FLAIR/T2. The most used scales are Fazekas [17] and age-related white matter changes (ARWMC) [76]. The WMC have variable size, but minimal diameter of the lesions at imaging > 1 mm (in any plane).

  2. (c)

    MICROBLEEDS should be evaluated in GRE T2*/SWI and the minimal diameter of the lesions at imaging is < 10 mm in any plane (Fig. 6). They could be a feature of small vessel disease (hypertension or cerebral amyloid angiopathy, CAA) and could be related to antithrombotic bleeding risk. All possible microbleeds mimics should be excluded (i.e., vessels, small cavernomas, mineralization foci, artifacts at the air-bone interface and due to partial volume, small hemorrhagic areas due to infarcts or other bleeds).

Table 5 Fazekas score
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Table 6 ARWMC rating scale for WMLs on MR imaging and CT
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Fig. 5
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Axial FLAIR images. On the left, one punctate lesion on the right frontal white matter (Fazekas 1); in the middle, confluent foci at retrotrigonal white matter; on the right, diffuse and confluent subcortical, peri and paraventricular white matter lesions

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Fig. 6
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Axial GRE T2*. On the left image and middle images, infratentorial [pons (n. 1), left middle cerebellar peduncle (n. 1) and hemisphere (n. 1)] and deep [right thalamus (n. 5), posterior putamen (n. 1)] microbleeds, correlated to systemic hypertension. On the right image 3 lobar microbleeds associated with Fazekas 3, in keeping with amyloid angiopathy

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An example of scale with high intrarater and interrater reliability is MARS (Microbleed Anatomical Rating Scale) which describes their number and location in lobar and/or infratentorial and/or deep regions [23].

  1. (d)

    SMALL VESSEL DISEASE (SVD) (see Figs. 5 and 6; Figs. 7 and 8) should be evaluated in FLAIR/T2, GRE T2*/SWI, and T1 acquisitions. Parenchymal changes such as (1) microbleeds; (2) lacunae; (3) perivascular spaces; and (4) white matter changes indicate the presence of small vessel disease, but each type of imaging finding has a different risk weight. In fact, the presence of a single lacuna or microbleed adds one point of the SVD score (Total 4 points) [69], which is equivalent to that of a severe enlargement of the perivascular spaces and/or Fazekas 3, thus indicating a higher risk of clinical consequence (ischemic and hemorrhagic brain events, dementia) [47].

Fig. 7
figure 7

Three-dimensional brain rendering showing an example of quantitative analysis. Yellow and pink colors indicate the brain areas which are respectively below the 5 and 25 percentiles of the reference population (measures normalized to the intracranial volume). Powered by QyScore®

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Fig. 8
figure 8

Guided report template

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  1. 3.

    Volumetric measures

    Visual differentiation between brain changes due to aging or to an early stage of the disease can be difficult, so the quantification of brain structures from a single patient and its comparison to age and sex-specific reference MRI data of healthy population can improve the diagnosis (Fig. 7). Several volumetric brain assessment methods and commercial Regulatory Authority approved (e.g., FDA, CE, CFDA marking) software are clinically available and implemented in radiology reporting, but without a clear strategy in the assessment. One way to improve the diagnostic accuracy of the use of the software in clinical practice is the double assessment—visual and quantitative—which combines the visual rating and the atrophy measurements [73].

  1. 4.

    Follow up

    If there are any vascular findings at MRI, an annual follow-up is recommended.

    In case of trials or other pathologies, the control MRI should be scheduled according to clinical indications.


(D) Reporting

  1. 1.

    A structured reporting is often not considered useful in clinical practice and could present other critical issues [74], so a guided report is preferable (Fig. 8). We recommend using the following template, modified from a previous ESNR dementia working group 2019 proposal.

Please consider that it is advisable to mention in the "Conclusions/Impressions" of the report:

  • Any individual differences from a control population (cross-sectional assessment) by applying the visual qualitative and rating scale or/and the volumetric assessment

  • Any stability or longitudinal worsening of the radiological findings (longitudinal evaluation) from previous radiological examinations, if appropriate for comparison

To do this, when evaluating brain atrophy, it is useful to take into account existing reference standards for assessing differences between a subject and the control population and individual rates of change over the life course even with respect to the trajectories of volumetric brain imaging markers [7, 75].

According to these large and inclusive datasets currently available (BrainChart open source and Rotterdam study), the trajectories of volumetric changes in gray matter, white matter, and third ventricles show nonlinear curves, with accelerated change with advancing age and some differences between men and women.

Regarding the "mixed pathology" reported in "Conclusions/Impressions," it should be emphasized that the diagnosis of "mixed dementia" is clinical, not neuroradiological. The neuroradiological description of, for example, hippocampal atrophy and Fazekas 3, does not mean that the patient's cognitive impairment is equally attributable to neurodegeneration and microangiopathy. It is up to the clinician to determine how much of the clinical picture is attributable to one or the other component.

Sample Case Report (in Supplemental material)

(E) Future avenues

In the future, the use of volumetric information in routine radiology may be increasingly widespread, and we recommend dual assessment (combining visual scoring with volumetry, see C 3). These measurements are reproducible and automatic, but are depending on scan protocol, software, and the reference population. Other critical issues include the limited access to volumetric tools in the clinical setting (data must be transferred to the workstation and results to the PACS), and the training required to properly read the results.

Differences between men and women in neuroimaging biomarkers of neurodegeneration are reported [7, 75] and these should be considered in the near future when normative reference values will be applied in a clinical setting to assess pathology in individual patients.

The new Alzheimer drugs (i.e., Aducanumab) are rapidly changing the clinical scenario and the role of MRI, leading to the need for specific MRI protocols and precise reporting of the side effects of ARIA (amyloid-related imaging abnormalities, referring to cerebral edema or microhemorrhages).

One of the next frontiers is the clinical application of artificial intelligence, as it can offer solutions and interpretation of complex, multimodal medical information, such as that provided by imaging (radiology and nuclear medicine), biology, and neurocognitive testing, thus improving the diagnostic and prognostic process. But the process of identifying international medico-legal rules is still at an early stage [51].

Discussion

To complement what was presented in the results, the main practical recommendation that emerged is to try to fit all the radiological steps presented—MRI protocol (B), image evaluation and interpretation (C), and reporting (D)—to the clinical diagnosis. Unfortunately, in radiological practice, there are still several general obstacles to this [74], such as:

(1) reduced confidence about the most correct approach to reading images (especially in the use of scales and volumetry), (2) report variability (with no use of structured or guided reports), and (3) generic requisition forms that do not allow radiologists to conclude whether imaging results are in line with clinical suspicion. The latter problem could be solved by better communication among specialists (e.g., at interdisciplinary meetings), which is essential in challenging clinical settings.

The use of all proposed scores is highly recommended, possibly accompanied by a visual description, except for MARS—which in routine is best replaced by a description of the number and distribution of microbleeds, according to the major patterns (superficial distribution in cerebral amyloid angiopathy versus deep infratentorial localization in hypertension)—and for the SVD score—which can be replaced by a description of the findings of small vessel disease according to the priority of their clinical relevance.

Although MRI findings are diagnostic only for a few conditions (e.g., late-onset AD, vascular dementia, CAA, iNPH, etc.), they support the clinical diagnosis of all forms of dementia (see Boxes, above) and provide important information on differential diagnosis, overlapping/coexisting forms (e.g., AD and VaD; FTLD and VaD; DLB and VaD), and possible side effects of new drugs.

More generally, neuroimaging is crucial for the diagnosis of dementia and is recommended in every patient with cognitive decline. In older adults, especially in the oldest old or in patients with multiple comorbidities, severe disability or behavioral disorders, completion of an MRI or nuclear imaging protocol can be troublesome, due to limited collaboration. The indications for the examination should be discussed with the treating physicians, ideally in a multidisciplinary team. Limited to these cases, volumetric CT is acceptable [2], at least to rule out some secondary and potentially reversible causes of cognitive impairment, such as subdural hematoma or brain masses.

Conclusions

The diagnostic process of cognitive disorders requires a combined assessment of the clinical picture and imaging, including CT, MRI, and nuclear medicine, and can only be achieved through the dialogue between disciplines and the ongoing review of shared knowledge, information, and reports.