There are three main findings of interest from this study. First, MRI volume of the angular gyri, one of the posterior cortical regions known to be implicated in the early neuropathology of AD, was moderately correlated with a direct assessment measure of financial abilities in patients with amnestic MCI. Second, angular gyri volume was shown to be a unique predictor of financial abilities after accounting for overall mental status and demographic variables. Third, the relationship of angular gyri volume with financial abilities was shown to be partially mediated by arithmetic ability. These findings have implications for understanding the pathway by which early declines in financial abilities can occur in amnestic MCI patients.
To our knowledge, the current study is one of the first to link brain measures in areas other than the hippocampus with IADLs in patients with amnestic MCI, demonstrating that structural brain measures are sensitive not only to cognitive and clinical impairments but also to emerging deficits in cognitively demanding IADLs such as financial capacity. Patients with amnestic MCI are known to experience brain volume changes that have implications for cognitive function and prognosis. Hippocampal atrophy in amnestic MCI corresponds to memory impairment26
and disease progression25
, and is predictive of risk of later “conversion” to AD44
. However, volumetric abnormalities also occur in other cortical regions in patients with MCI, such as the posterior cingulate45
and angular gyrus46, 47
. Our data generally correspond with these prior findings: the hippocampal volumes were significantly smaller in amnestic MCI compared to controls. While the other ROIs did not reach significance, they were smaller in patients compared to controls in all instances, and in the case of the angular gyrus over 1/3 of the MCI patients showed emerging volumetric abnormalities (values below −1 SD
Furthermore, these data suggest that angular gyri volume, and the neural networks that it is a part of, is a specific neurocognitive substrate by which financial capacity is influenced. The first evidence supporting our conclusion is that, despite high intercorrelations among the volumetric ROI in our sample, other brain volumes including the hippocampus were meagerly correlated with FCI performance, whereas the angular gyri volume showed a reasonably robust correlation. An exploratory VBM analysis showed a strong trend for a cluster of voxels located in the posterior parietal cortex in the area of the angular gyrus to predict FCI scores. Additionally, regression demonstrated that the volumetric predictor of FCI in our MCI patient sample was angular gyri volume. The third evidence in support of a specific relationship between angular gyri volume and FCI performance is the more stringent regression model that accounted for overall mental status, age, education, and sex (factors that would plausibly influence performance on financial abilities). Despite adjustment for these covariates, the angular gyri volume remained a key predictor of FCI performance, uniquely accounting for 12% of variance in scores. It could be argued that the relationship of MRI volumes with financial abilities and IADLs is simply a proxy for the effects of global cognitive change on IADLs. However, our data suggest that there is a specific relationship between financial abilities and angular gyri volume in patients with amnestic MCI.
Another key finding is the demonstration that arithmetic abilities, and to some extent attention, mediate the relationship of angular gyri volume with financial abilities in patients with amnestic MCI. The amnestic MCI patients in this study were impaired relative to the matched controls on performance of the FCI, consistent with our prior reports4, 9
. The Arithmetic score was the primary neurocognitive predictor of overall financial abilities in a prior study using a larger amnestic MCI sample and the full FCI instrument10
. Our findings add further confirmation of the importance of arithmetic ability to financial abilities by demonstrating the link with brain volumetrics of the angular gyri. Prior studies have demonstrated a role for the angular gyri in calculation abilities48–50
, and a recent study linked regional metabolic abnormalities of the angular gyri with dyscalculia in AD12
. Our data add to the literature by demonstrating an association between angular gyri volume and calculation ability in amnestic MCI patients, and extending this finding to everyday financial tasks. Attention is also possibly a mediator of the relationship of the angular gyri volume with FCI in our patients. In a prior study, an attention composite score that included Spatial Span was predictive of FCI domain scores in MCI patients9
. Posterior lateral cortical regions such as the angular gyri have been implicated in attention deficits in patients with AD13
Brain structures that show changes in early AD and MCI, such as the angular gyrus and posterior cingulate, are components of larger neural networks that are responsible for neurocognitive processes51, 52
. In turn, changes in these neurocognitive processes likely result in impairment in complex daily activities. One such critical network that has received increasing attention is the default mode network, in which abnormalities have been detected in patients with AD53
. This network has been implicated in executive function55
, and goal directed behavior57
, and as such is likely a primary neural system mediating cognitive functions subserving complex daily activities. Thus, the current findings are an initial effort to identify brain structures that underlie neural network degradation associated with changes in complex daily activities.
One potential issue to address is the amount of overlap between the FCI and the WRAT-3 Arithmetic score. Both measures are strongly correlated (.74) and the Arithmetic measure predicted 55% of the variance in FCI scores. The financial domains measured by this version of the FCI were financial conceptual knowledge, bank statement management, financial judgment, and bill payment. Of these, only the financial conceptual knowledge domain directly involves calculations (i.e., figuring percentages on tax). The other domains assess abilities such as demonstrating knowledge regarding financial affairs (i.e., bank statements, bills, taxes), locating information on bank statements and bills, organizing bills, and exercising financial judgment in fraud scenarios. In an exploratory analysis of correlations with domain- and task-level performance on the FCI, we found that angular gyri volume is correlated with both conceptual tasks as well as pragmatic tasks requiring calculation (data not shown). Certainly, application of written arithmetic problems such as those measured by the WRAT-3 requires not only calculation abilities but conceptual knowledge regarding calculations (i.e. division, fractions, percentages), visual scanning, and working memory (for instance, see the correlation of Arithmetic scores with Spatial Span in ). We previously reported that performance on WRAT-3 Arithmetic was impaired in patients with AD, who showed a variety of errors such as operation substitution (addition rather than subtraction) that indicate possible degradation of semantic knowledge regarding calculations, as well as digit substitution and other inattentive errors58
. One possible implication is that the angular gyri are important not only for performance of calculations, as well as reading and writing50, 59
, but also for knowledge of mathematic operations and financial concepts as well. Such a supposition would certainly require further study.
Our study represents one of the first to directly link structural brain measures in amnestic MCI with a direct-assessment measure of financial abilities. A grossly neglected area of research has been investigations of the neuroanatomical basis of changes in IADLs in older adults using neuroimaging. Only a few such studies have been reported, and none to our knowledge with a clinically-diagnosed population of amnestic MCI patients. In one study MRI volumes of cortical gray matter and the hippocampus were predictive of contemporaneous clinician ratings of IADLs based upon caregiver interview in healthy individuals and patients with AD18
. Another study using an informant-based rating of IADLs (IQCODE) examined the correspondence of these ratings with hippocampal volume and white matter hyperintensities in a mixed group of English and Spanish speakers, some of whom were cognitively impaired based upon psychometrically-defined thresholds21
. The uniqueness of the current study compared to these other reports is the focus on direct assessment of a specific IADL, investigation of several ROIs, and study of a clinically-diagnosed group of patients with amnestic MCI. Additionally, our focus on MRI volumes within the MCI group likely influenced the lack of findings in the hippocampus, as both prior studies included imaging data from cognitively normal individuals in their statistical analyses. Other authors have indicated that hippocampal volumes in patients with AD may fail to correspond with behavioral measures as an artifact of the extensiveness of hippocampal atrophy and more widespread effects to other brain regions60
. Such factors may plausibly be at play in patients with MCI as well.
The clinical and future research implications of the current findings are grounded in the importance of understanding IADL changes for clinicians and families. Decline of IADLs is the phenomenological “face” of dementia to patients with AD and their families, as they typically require increasing oversight and engagement of family members in the care of these patients. Changes in IADLs such as financial capacity moreover have public health significance, as such changes can be important markers of disease progression in MCI and are a crucial diagnostic criterion for clinically detecting conversion to dementia. Although it has been increasingly appreciated that cognitive changes in MCI can lead to changes in IADLs, we do not yet understand how neurodegeneration of key neural pathways lead to deficits and declines in IADLs. Such knowledge would be important for researchers to develop comprehensive models of IADL declines and will assist in early identification and care as well as inform diagnosis and support instrument development.
Limitations of the current study should be acknowledged. Our approach to volumetric analysis may not correspond directly with volumetrics derived from manually traced volumes, and results obtained using such methods may not be directly comparable. Other findings have suggested that SPM-based approaches have high correspondence with manual tracing39
. Persons with amnestic MCI in this study are undergoing longitudinal follow-up as part of their participation in the UAB ADRC. As the current paper is a cross-sectional study, the ultimate clinical and neuropathological status of these participants is unknown. Our Center's observed rates of conversion to AD from amnestic MCI is consistent with the conventional annualized 15% rate of risk61
, indicating that a majority of the participants in this study will likely clinically manifest AD in the future. Correspondence of findings in a sample of mild AD patients would also be desirable.
In conclusion, we present findings supporting a relationship between MRI brain volumes and IADL deficits in patients with amnestic MCI. Financial abilities showed a robust relationship with volume of the angular gyri, and this relationship was partially mediated by a measure of arithmetic abilities and possibly also by attention. These findings hold promise for further investigation of IADL declines in amnestic MCI and mild AD using neuroimaging techniques in order to increase our knowledge of how brain atrophy and corresponding pathology and cognitive change may place these patients at high risk for changes in complex daily activities such as financial capacity.