Features of changes in fractional anisotropy of different brain parts during the progression of Parkinson's disease

Full Text

BACKGROUND

Parkinson’s disease (PD) is a neurodegenerative disorder with the second-highest incidence worldwide, after Alzheimer’s disease. The clinical manifestations of PD mostly result from the demise of dopaminergic neurons within the substantia nigra (SN). However, as this disease advances, neurodegenerative transformations occur in nearly all brain structures [1].

Several studies on PD, alongside morphometric indices, have evaluated the brain’s structural connections using diffusion-tensor magnetic resonance imaging (DT MRI). This technique enables the assessment of microstructural brain disorders in vivo and relies on measuring the magnitude and directionality of water molecule diffusion within each voxel of the image. Water diffusion occurs along a preserved axon fiber because it has an insulating myelin sheath, indicating its direction and integrity. This is the basis for acquiring DT images. DT MRI visualizes and quantitatively evaluates the condition of brain conductive pathways [2].

The quantity of DT MRI studies in patients with PD is quite less. Nonetheless, available data demonstrate that this approach can enhance the quantity and value of the diagnostic information obtained.

A study [3] discovered that cognitive disorders in patients with PD are linked to specific characteristics of brain tractography. A reduction in working memory capacity was consistently associated with reductions in fractional anisotropy (FA) of the brain’s conductive pathways in the left temporal region, head and tail of the right hippocampus, head of the left hippocampus, knee of the corpus callosum, and left orbitofrontal region. The “disruption of ascending fibers within the corpus callosum” may serve as a neuroimaging biomarker for dementia progression in PD.

Langley et al. used DT MRI data from 20 patients with stage III PD assessed according to the Hoehn and Yahr scale and from 17 healthy volunteers [4]. The authors identified changes in regional FA within the SN. A substantial decline in the FA of the SN was observed in patients with PD compared with that in control participants, specifically in rostral areas more than in caudal sections. Abnormalities were observed in the SN of the hemisphere opposite to the limbs, exhibiting the most significant neurological symptoms.

The role of extranigral pathology in causing nonmotor disorders and the link between cognitive disorders and psychotic symptoms were observed by the staff of the Department of Nervous Diseases of the Academy [5, 6]. However, the precise progression of the conductive pathway changes from PD stages II to III remains inadequately understood.

The discrepancy in the obtained results can be attributed to the limited sample of patients studied and variances in the methodologies employed. In most studies, structural interrelationship disorders were found in patients with PD, mainly in the SN and striatopallidal complex and in some cases in the cerebellum. In addition, patients with cognitive impairments exhibited a decrease in FA within the left temporal region, hippocampus, and corpus callosum. These observations hint at the possible nature of disease progression and potentially introduce new therapeutic approaches.

If the confirmed data from subsequent studies demonstrate that the measurement of FA of the listed tracts can be useful for the differential diagnosis of various parkinsonism syndromes, the data can help in prescribing appropriate therapy at an earlier stage.

Currently, cortical lesions manifest in the later stages of the disease. However, there remains interest in studying the precise involvement of brain structures in the pathological process during disease progression [7].

This study aimed to examine the distinctness of lesions in cerebral conductive pathways during the progression of PD using MR tractography data.

MATERIALS AND METHODS

Eighty-eight patients with PD were assessed based on the diagnostic criteria set by the British Brain Bank [8]. These patients were divided into 2 groups according to the disease stage and criteria stipulated by the Hoehn and Yahr scale: 42 patients with stage II and 46 with stage III. All study participants were receiving therapy with dopaminergic drugs at the time of inclusion.

The control group comprised 35 individuals of comparable age who exhibited initial symptoms of cerebral circulation insufficiency.

The patients were subjected to neurological examinations that included evaluations of their motor functions. The degree of motor disorders, such as hypomimia, gait disorders, posture, trunk bradykinesia, rigidity, tremor, and postural instability, was measured according to Section III (motor functions) of the Unified PD Rating Scale (Fahn S, Elton S, et al.), a dedicated tool for diagnosing such disorders. The clinical stage of the disease was evaluated using the Hoehn and Yahr scale. All patients and controls underwent DN MRI.

A 3.0-T brain MRI was conducted using an 8-channel head coil on a Philips Achieva machine. The obtained results were projected onto a standard brain mask.

FA was measured on a scale from 0 to 1, where 0 indicates unrestricted diffusion and 1 represents the complete directional movement of all water molecules along the conductor’s axis. The functionality of a white matter conductor is contingent on its FA level, which is directly related to its integrity.

Statistical analysis was performed on 390 gray and white matter structures. Data were processed using Statistica 10.0 from StatSoft.

Data with normal distribution were described using the mean (M) and standard deviation (SD). Reliable differences were determined by a significance level of p < 0.05.

RESULTS

Statistically significant differences were discovered in the FA of several brain regions in patients with PD and controls. Specifically, the left hippocampus, short gyrus islet cortex, inferior temporal sulcus cortex, putamen, right superior temporal tract, left middle temporal tract, left and right red nucleus (RN), and subthalamic nucleus (STN) on the left showed significant variation (Table 1).

 

Table 1. Fractional anisotropy indices of the brain regions investigated in patients with Parkinson’s disease that showed significant differences
Structure	Comparison group, M ± SD	Stage II on the Hoehn and Yahr scale, M ± SD	Stage II on the Hoehn and Yahr scale, M ± SD	р-value
Left hippocampus	–	0.194 ± 0.004	0.216 ± 0.007	0.024
Insular cortex gyri	–	0.179 ± 0.004	0.197 ± 0.004	0.014
Inferior temporal cortex	0.226 ± 0.127	0.236 ± 0.007	0.268 ± 0.005	<0.05
Superior temporal cortex	0.248 ± 0.006	0.249 ± 0.006	0.276 ± 0.005	<0.05
Left putamen	–	0.340 ± 0.004	0.196 ± 0.007	0.046
Left RN	–	0.415 ± 0.017	0.489 ± 0.022	0.023
Right RN	–	0.474 ± 0.01	0.532 ± 0.02	0.026
Left STN	0.358 ± 0.046	0.531 ± 0.03	0.512 ± 0.036	<0.05
Right rubrospinal tract	0.431 ± 0.422	0.402 ± 0.38	–	0.009
Right medial longitudinal fascicle	0.46 ± 0.44	0.421 ± 0.4	–	0.037
Right inferior cerebellar peduncle	0.4 ± 0.39	0.37 ± 0.35	–	0.047

 

As the PD stage increased, a significant increase in FA was found in the left hippocampus, insular gyrus cortex, superior and inferior temporal sulci, right and left RN, and left STN. Moreover, the FA of the putamen on the left side consistently decreased.

Patients with PD showed a significant decrease in the FA of the rubrospinal tract, medial longitudinal fasciculus, and inferior cerebellar peduncle on the right side (Figures 1–3).

 

Fig. 1. Visual comparison of the right inferior cerebellar peduncle between the controls and patients with stage II Parkinson’s disease (PD) using the Hoehn and Yahr scale

 

Fig. 2. Visual comparison of the right rubrospinal tract between the controls and patients with stage II Parkinson’s disease (PD) using the Hoehn and Yahr scale

 

Fig. 3. Visual comparison of the right medial longitudinal fascicle between the controls and patients with stage II Parkinson’s disease (PD) using the Hoehn and Yahr scale

 

DISCUSSION

The use of DT MRI in PD studies is limited; however, evidence indicates that the progressive decline in the function of various tracts can disrupt the integrity of the conductive pathways between cortical and subcortical regions associated with specific cognitive functions [9].

The study identified significant increases in the FA in certain gray matter structures of the brain in patients with PD. Specifically, the left hippocampus, insular gyrus cortex, and inferior and superior temporal sulcus cortices showed notable changes.

According to Chen et al., FA values were reported to be higher in the hippocampus and temporal gyrus regions of the cerebral cortex in patients with PD than in healthy controls [10]. The hippocampus and temporal cortex are responsible for cognitive functions, which suggests that the increase in FA may be attributed to compensatory functions.

Herz et al. conducted a meta-analysis of functional neuroimaging studies on motor tasks and reported consistently reduced FA in the posterior putamen of patients with PD while performing motor tasks [11]. In this study, we replicated these findings by observing a nearly twofold decrease in FA in the left hemisphere of patients with stage III PD according to the Hoehn and Yahr scale.

In addition, patients with PD exhibited an increase in FA within both the left and right RN and STN regions.

The RN is an objective subcortical center that plays a pivotal role in movement coordination. Its bilateral connection with the cerebellum and cortex allows it to proficiently participate in motor control. Presumably, increased FA amplifies RN activity to compensate for the dysfunctional thalamostriatocortical circuit.

STN plays a crucial role within the basal ganglia–thalamocortical circuit. Studies have suggested that STN overactivity may be responsible for the symptoms of PD [12]. Moreover, Wang et al. reported that problems concerning basal ganglia and thalamocortical connections may result in bradykinesia and rigidity [12].

Patients with newly diagnosed and moderately severe PD exhibit heightened functional connectivity between the STN and sensorimotor cortex, which implies that these changes occur in early disease stages [13]. This study revealed that the FA of the left hemisphere of the STN increases with disease progression.

In addition to the gray matter, modifications affect the neuronal pathways of the brain. Patients diagnosed with stage II PD showed FA reduction in the rubrospinal tract, medial longitudinal bundle, and inferior cerebellar peduncle on the right.

The Mormina et al. study analyzed the FA of the conductive pathways of patients with PD at the base of the peduncles and cerebellar hemispheres, comparing results from those with the disease for more than 5 years to healthy volunteer controls [14]. A decrease in FA was found in the cerebellar hemispheres of patients with PD, likely due to the inclusion of patients with longer disease duration.

Another study discovered an association between higher PD stages and longer disease duration with cerebellar white matter changes and decreased FA [15].

The medial longitudinal fasciculus belongs to the global coordinator and cognitive system [16]. The malfunction of this pathway causes coordinator and postural disorders in PD and cognitive decline.

Furthermore, patients with PD exhibited a decrease in FA within the rubrospinal tract. The rubrospinal tract primarily transmits information related to the nature of purposeful movements and the occurrence of tremors that are symptomatic of PD.

CONCLUSIONS

The data indicate a reduction in the FA in the brain’s conductive pathways and subcortical formations, implying their dysfunction. By contrast, FA increases in different cortical regions. The latest established finding is a result of the cortical compensatory response to lesions of the conductors and basal ganglia.

Thus, MR tractography augments the amount and caliber of diagnostic information acquired from patients with PD and serves as a method of evaluating disease progression. Moreover, this approach enhances and broadens the understanding of PD causes.

ADDITIONAL INFORMATION

Funding. The study was conducted without the use of sponsorship funds or financial support.

Conflict of interest. The authors declare no obvious and potential conflicts of interest related to the publication of this article.

Ethical review. The study was approved by the local ethical committee of the Kirov Military Medical Academy of the Ministry of Defense of the Russian Federation (Minutes No. 243 of 10/20/2018).

Author contributions. All authors made a significant contribution to the study and preparation of the article and read and approved the final version before publication.

About the authors

Irina A. Vlasova

Military Medical Academy; North-Western district scientific and clinical center named after L.G. Sokolov

Email: a629100@yandex.ru
ORCID iD: 0000-0001-5796-9814

M.D., Neurologist

Russian Federation, Saint Petersburg; Saint Petersburg

Artem G. Trufanov

Military Medical Academy

Author for correspondence.
Email: trufanovart@gmail.com
ORCID iD: 0000-0003-2905-9287
SPIN-code: 7335-6463
Scopus Author ID: 55543694800

M.D., D.Sc. (Medicine), Associate Professor of the Nervous Diseases Department

Russian Federation, Saint Petersburg

Igor' V. Litvinenko

Military Medical Academy

Email: litvinenkoiv@rambler.ru
ORCID iD: 0000-0001-8988-3011
SPIN-code: 6112-2792
Scopus Author ID: 35734354000
ResearcherId: F-9120-2013

M.D., D.Sc. (Medicine), Professor

Russian Federation, Saint Petersburg

Miroslav M. Odinak

Military Medical Academy

Email: odinak@rambler.ru
ORCID iD: 0000-0002-7314-7711
SPIN-code: 1155-9732
Scopus Author ID: 7003327776
ResearcherId: I-6024-2016

M.D., Corresponding Member of the Russian Academy of Sciences, D.Sc. (Medicine), Professor

Russian Federation, Saint Petersburg

References

Supplementary files