Introduction

Vascular dementia is the second most common cause of dementia worldwide, surpassed only by Alzheimer's disease. Its heterogeneous pathology and clinical presentation contribute to a unique identity among its counterparts, thus, need for different diagnostic criteria and approaches. The disease affects a large proportion of the elderly population.1 2 Notably, despite its heterogeneous nature, it remains a foremost preventable cause of cognitive impairment if diagnosed early.

Vascular cognitive impairment, a relatively newer term, is used3 to denote cognitive impairments that occur due to a cerebrovascular cause, ranging from mild cognitive impairment stage to vascular dementia. Predominantly, it comprises cerebral small-vessel disease, large-vessel disease, or a combination of both.2 4 5 6 Cognitive dysfunction after a stroke occurs in approximately two-thirds of the patients, which may be followed by complete or incomplete recovery.3 The pattern and severity of cognitive dysfunction often depend on the location of the lesions within the brain. Different clinical manifestations in the large-vessel disease depend on the arterial territory involved; consequently, multiple domains may be involved due to arterial territory lesions in different cortical and subcortical locations.3 7 8 9 For instance, memory impairment is more often lesion specific, that is, involvement of the medial temporal lobes affects the episodic memory, whereas lesions in the cortices affect different aspects of long-term memory.10 11 12 Those with frontal lobe infarcts tend to have more of retrieval defect than those with middle cerebral artery (MCA) territory involvement emphasizing on the role of the prefrontal cortex in memory. Likewise, visual memory impairment is seen in lesions of the right medial temporal lobe,13 and attention requires a multilobar orchestration between the dorsolateral and ventromedial prefrontal cortices, and the posterior parietal cortex.14

Furthermore, the type of cognitive and behavioral domain affected and the hemisphere involved also affect the severity of dementia, and thus, the patient's functional ability and status.15 16 Therefore, delineating the role of vascular involvement is crucial not only for the clinical diagnosis and prognosis but also for the functional rehabilitation and care of such patients. In this regard, we conducted this study with the primary objective to examine the cognitive dysfunction in large-vessel vascular dementia. Secondarily, we aimed to delineate cognitive dysfunction in large-vessel vascular dementia as per the arterial territory involvement in these patients. Additionally, we evaluated the contribution of hemispheric involvement with respect to the patient's functional status as evident from the clinical dementia rating (CDR).

Materials and Methods

This index paper is part of a larger study that was conducted to explore the epidemiological aspects of vascular dementia in Kolkata (eastern zone of India). Prior approval from the institutional ethics committee was obtained.

The current observational cross-sectional study was performed at the department of neurology at a tertiary care center in Kolkata, India between March 2017 and October 2018.

Results

Twenty-eight (36.8%) of our patients had large-vessel disease (based on the NINDS-AIREN criteria). With a mean age of 56.6 ± 5.2 years, 9 (32.1%) patients were female and 19 (67.9%) patients were male. The mean mini-mental state examination (MMSE) of these patients was 18.54 ± 1.59. Regarding the risk factors for stroke, hypertension was the most prevalent in the overall group, followed by smoking, diabetes, and hyperlipidemia.

Discussion

Most of our patients had an abrupt onset and a stuttering course as has been reported in previous studies.12 The presence of executive and attention dysfunctions in the anterior cerebral artery (ACA) territory infarcts can be attributed to the role of the dorsolateral prefrontal cortex and its connections in the executive function as well as attention, whereas the calculation defect in these patients could be secondary to executive dysfunction or lack of attention. Further, behavioral dysfunction in patients with ACA territory infarcts could be due to the involvement of the frontal cortex, especially the dorsolateral prefrontal, the orbitofrontal, and the medial prefrontal cortex, which are responsible for behavior. Lesions in these areas have been linked to behavioral dysfunction and abnormal behavior in some previous studies.11 18 Therefore, the presence of significant association of impaired attention, executive dysfunction, and behavioral dysfunction with the ACA territory lesions in our group further corroborates the role of these areas in attention, behavior, and executive function.

The MCA territory infarcts largely led to memory and language dysfunction, along with visuospatial dysfunction and apraxia. Since the MCA territory predominantly involves both the anterior and posterior language areas, there is a high possibility of language disorders in these patients.19 20 21 It is also known that damage to these areas can cause various types of language abnormalities.22

Memory is also a function of the medial temporal lobes, the left is mainly concerned with verbal memory, while the right is concerned with visual memory.23 24 25 This explains the involvement of memory in the patients having infarcts in the MCA territory. Most commonly, the episodic memory was affected which did not improve on giving cues, thus proving that the memory involvement was cortical rather than subcortical. Two patients having lesions in the right medial temporal lobes had visual memory impairment. Likewise, the presence of apraxia in MCA territory strokes could be explained by the blood supply of the praxis pathway and neuroanatomical substrates.26 27 28 29

Visuospatial dysfunction was seen in MCA territory strokes with right-sided involvement, and all these patients showed involvement of the parietal cortex. The visuospatial function is a feature of the right parietal cortex and its connections. Further, this dysfunction also occurred in the lesions of the PCA territory which may be attributed to the involvement of the pathway comprising the occipitoparietal areas and their connections.30 31 Similarly, occipitotemporal lesions led to disruption of the “what” pathway causing the visuoperceptual dysfunction in the form of visual object agnosia and prosopagnosia.

In our study, we found attention and executive dysfunction followed by calculation to be more impaired in ACA territory infarcts. The association was significant in domains of attention, executive dysfunction, and nearly significant in case of behavior for ACA territory lesions. Among other cognitive domains, our results could not achieve statistical significance for any domain. This may have been because of the small sample size in our study, and a lack of quantitative cognitive scoring for various domains which could have provided a better overview and comparison among the various subgroups. Nevertheless, we could still infer that attention and executive function were significantly impaired for ACA territory lesions.

We also compared the patients' functional status with respect to the hemispheric involvement using the CDR scale. Patients with lesions on the right side were compared with patients having lesions on the left side or bilateral lesions. There was a significant difference in the mean CDR between the two groups—those with lesions on the left side or bilateral lesions had a higher mean CDR than patients with right-sided lesions. This implies that vascular cognitive impairment in large-vessel disease might be more severe when presenting on the left side. Considering that the left side is the dominant hemisphere, and all our patients of large-vessel disease were right handed, we can presume that left-sided lesions are involved in a majority of cognitive functions, including executive function, verbal memory, and attention. Also, these patients had a lower MMSE when compared with the patients on the right side. Thus, our results suggest that laterality affects the severity of vascular dementia in large-vessel disease. A CDR score of 3 was present in left-sided lesions or bilateral lesions and not in patients with right-sided lesions. Our findings are supported by previous studies which have also reported asymmetry in the dementia severity and functional status depending on the hemisphere involved or the cognitive domain affected.15 16 32 We also compared the mean CDR scores in between the arterial territories. Although the mean CDR was higher for MCA territory infarcts, we could not find any statistically significant difference in between the groups. This could be due to the small sample size of our study. Moreover, we could not measure the infarct volume in these patients. Nevertheless, it implies that the cognitive impairment in MCA territory infarcts was more severe than ACA and PCA territory infarcts, respectively.

We did not observe any association between gender and the arterial territory involved, which implies that gender has no effect on the arterial territory in these patients. Furthermore, there was no difference in the mean MMSE between the three groups of left-sided, bilateral, and right-sided lesions. Thus, MMSE was disturbed irrespective of the arterial territory involved or the laterality of the lesion in patients with vascular cognitive impairment. Although MMSE is a reliable screening tool for dementia, it has many limitations, such as a lack of frontal assessment or the inability to administer MMSE in patients having features predominantly of frontal lobe dysfunction.33 The above factors could have affected our findings, especially in patients having features of frontal lobe dysfunction. Many previous studies have studied the MMSE in vascular dementia patients; however, these studies did not subcategorize them based on the arterial territory or hemispheric involvement.11 15 34 35

Strengths

Our study is one of the few endeavors to examine all cognitive domains in vascular dementia and compare between different arterial territories and the right and left hemispheric lesions. We excluded all patients of mixed vascular and degenerative etiologies, as well as mixed large- and small-vessel diseases.

Limitations

Some potential limitations of our study are worthy of mention. Functional and diffusion tensor imaging was not available for the present study due to financial and logistic constraints. These methods could have helped objectively corroborate our clinical findings. We excluded patients with mixed dementia who had a concomitant degenerative pathology to remove possible sampling bias. The use of histopathological examination could have substantiated our results.

Conclusion

The above findings suggest that the nature of cognitive impairment varies with different arterial territory lesions in large-vessel disease and delineating the specific subtypes and their anatomical distribution can aid in predicting the clinical course and diagnosis. We also observed that executive dysfunction, calculation, attention, and behavioral dysfunction were more prevalent in ACA territory infarcts, while memory, language, and apraxia were more frequent prevalent with MCA territory infarcts, and agnosia and visuoperceptual dysfunction were more commonly observed with PCA territory infarcts. However, this can only be substantiated by functional or diffusion tensor imaging studies. Also, hemispheric involvement is an important predictor of dementia severity. Memory dysfunction is an important contributor to the severity of dementia, and those with right-sided involvement have less severe dementia as compared with those with left-sided or bilateral lesions.