Regular Research Article
Clinical and MRI Predictors of Conversion From Mild Behavioural Impairment to Dementia

https://doi.org/10.1016/j.jagp.2019.12.007Get rights and content

Highlights

  • We aimed to 1) identify the differences in baseline clinical and magnetic resonance imaging (MRI) features associated with conversion to a neurodegenerative disease in the following four years; 2) validate, based on these data, some easy-to-use clinical and MRI criteria that could help to identify, at the individual level, those MBI subjects at higher risk to receive a clinical diagnosis of dementia over time.

  • We found that the presence of an executive deficit, severe theory of mind impairment, and the presence of isolated frontal atrophy (i.e., with a spared volume within the remaining cortical regions) were associated with a higher risk of progression from MBI to a clinically evident neurodegenerative condition over the following 4 years.

  • Our results suggest that identifying MBI in the general population would help identify patients who would later present with bv-FTD.

Abstract

Objective

As an analogy with mild cognitive impairment (MCI), the mild behavioral impairment (MBI) construct has been proposed as a diagnostic label for those presenting late-onset behavioral symptoms. To date, however, the clinical, cognitive, and structural imaging features associated with an increased risk of conversion from MBI to dementia are poorly understood.

Methods

We retrospectively analyzed the cognitive performance and structural brain MRI of 113 subjects, with a clinical follow-up of at least 4 years available. Subjects were randomly assigned to a Group A (56 subjects; age: 65.4 ± 7.9 years, 15 females, MMSE score: 28.4 ± 2.3)) or to a Group B (57 subjects, age: 66.6 ± 6.4, 17 females, MMSE score: 28.0 ± 1.4). In the Group A, cognitive and structural variables were compared between converters (at 4 years) and nonconverters and then verified in the Group B group.

Results

In the Group A, 14 patients converted to behavioral-variant of frontotemporal dementia (bv-FTD) and 4 to Alzheimer's Disease (AD). Converters presented at baseline lower executive function scores and total Theory of Mind (ToM scores), as well as more severe focal frontal atrophy. In the Group B, 13 subjects converted to bv-FTD and none to AD. The combination of the variables identified in the Group A significantly (p <0.001) discriminated between converters and nonconverters in the Group B with a sensitivity of 0.615 and a specificity of 1 (total accuracy 91.22%).

Conclusion

The combined presence of executive deficit, impaired ToM, and presence of isolated frontal atrophy was associated with risk of progression from MBI to a clinically evident neurodegenerative condition, mainly bv-FTD, over a 4-year period.

Introduction

Recent years have seen an increasing interest of the clinical community for newly developed behavioral symptoms as a possible early manifestation of neurodegenerative disease, mainly the behavioral-variant of frontotemporal dementia (bv-FTD),1 but also progressive supranuclear palsy (PSP), Alzheimer's disease (AD), and dementia with Lewy bodies (DLB).2

The observation of a possible role for behavioral symptoms as an early “red flag” for the development of a brain neurodegenerative disease led to the development of a new diagnostic entity, i.e., mild behavioral impairment (MBI), mirroring the successful mild cognitive impairment (MCI) construct.

Tarangano et al. (2003)3 defined the MBI syndrome as consisting of persistent newly developed behavioral changes and mild neuropsychiatric symptoms, no serious cognitive complaint and normal activities of daily living (summarized in Table 1). The presence of MBI has been associated with an increased risk of progression to dementia.2,4, 5, 6, 7

Like MCI, that has an annual conversion rate to AD dementia of 31%,8 MBI is a heterogeneous condition, which includes late-onset psychiatric disorders (i.e., the development in late adulthood of primary psychiatric disorders in subjects with a negative psychiatric history), chronic cerebrovascular damage, and neurodegenerative diseases. To increase the clinical relevance of MBI, it is needed to identify those features that characterize the presence of a subclinical neurodegenerative process as the underlying cause of MBI.

Here, focusing on a naturalistic cohort presenting to a behavioral neurology/adult psychiatric service for the onset of newly developed and progressive social difficulties, we aimed to 1) identify the differences in baseline clinical and magnetic resonance imaging (MRI) features associated with conversion to a neurodegenerative disease in the following 4 years; 2) validate, based on these data, some easy-to-use clinical and MRI criteria that could help to identify, at the individual level, those MBI subjects at higher risk to receive a clinical diagnosis of dementia over time in an independent MBI set.

Section snippets

Patients

Using a retrospective approach, we identified all subjects who came to the attention of our behavioral neurology/adult psychiatric services between 2007 and 2014 for the onset of informant-confirmed, newly-developed and progressive behavioral symptoms who fulfilled the following criteria: 1) age between 60 and 75 years, 2) at least 8 years of formal education, 3) development of new behavioral deficits fulfilling current MBI criteria1,9 (such as reduction of empathy, emotional callousness,

Group A: Baseline Demographics, Clinical, MRI Characteristics and Conversion Rate

Demographic and clinical data for the Group A are reported in Table 3. There was no difference in age, sex distribution, education, and MMSE score between converters and nonconverters.

At 4 years, we observed that 18 patients converted to dementia during the follow-up (14 to bv-FTD28 and 4 to AD29 and; the cumulative 4-year conversion rate was thus 18of 56 (32.14%).

As compared to nonconverters, converters showed at baseline a lower executive function composite and total RMET scores and a higher

Discussion

In this retrospective study, we evaluated which clinical characteristics and conventional MRI features were associated with the risk of conversion from MBI to dementia over time.

Overall, we found that the presence of an executive deficit, severe theory of mind impairment and the presence of isolated frontal atrophy (i.e., with a spared volume within the remaining cortical regions) were associated with a higher risk of progression from MBI to a clinically evident neurodegenerative condition over

Disclosure

Disclosures: None except Matteo Pardini reports research support from Novartis and Nutricia and fees from Novartis, Nutricia and Merk.

Jordan Grafman acknowledges the support of the Smart Family Foundation of New York and the Therapeutic Cognitive Neuroscience Fund.

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    This work was partially supported by a Curiosity-Driven grant from the University of Genoa to MP.

    Presented at SIN 2019, Bologna 12-15 October 2019.

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