INTRODUCTION

Rising life expectancy in Indonesia, which in 2024 reached 70.32 years for men and 74.21 years for women, has driven a rapid expansion of the older population [1]. Approximately 27.08 million people, or 9.99% of the population, are now classified as older adults, and this demographic shift has been accompanied by a growing burden of degenerative and vascular disease, including stroke, whose prevalence among older adults is reported at 4.4% [2]. Globally, stroke is the second leading cause of death and the third leading cause of disability, and in-hospital mortality in the acute phase has been reported at 14.7% among patients managed in general wards, compared with 6.9% among those treated in dedicated stroke units [3].

Acute stroke represents the initial phase of the disease, during which brain tissue injury evolves rapidly and the degree of functional impairment is largely determined by the extent and location of the hypoxic territory. Beyond motor, sensory, speech, swallowing, and continence deficits, stroke frequently produces psychological and cognitive sequelae, including anxiety, depression, emotional dysregulation, and cognitive dysfunction [4]. Impaired cerebral perfusion is the central mechanism underlying vascular cognitive impairment (VCI), a spectrum that ranges from mild cognitive impairment (MCI) to post-stroke dementia and manifests as disturbances of thinking, memory, concentration, and emotional regulation [5]. In the acute phase, ischemia, inflammation, and oxidative stress cause neuronal injury that accelerates cognitive decline, while pre-existing vascular pathologies, including atherosclerosis, small vessel disease, cerebral amyloid angiopathy, and cerebral microbleeds, further contribute to cognitive dysfunction [6]. Cognitive impairment is highly prevalent in the early period after stroke, with reported rates exceeding 70%. Assessment in the acute phase is considered to capture the direct effect of the cerebrovascular event on brain function more faithfully than later assessment, because recanalization, reperfusion, and neuroplasticity during the first three to six months may partly mask the initial deficit [7]. Stroke severity, most commonly quantified with the National Institutes of Health Stroke Scale (NIHSS), is an additional determinant of outcome; the NIHSS is widely recommended as a valid and globally accessible instrument for treatment planning and prognostication [8].

The severity of post-stroke cognitive impairment is shaped by age, sex, education, vascular risk factors, and comorbidities. Lesion location, and in particular the hemisphere involved, has attracted increasing attention because of functional brain lateralization. Approximately 90% of right-handed and 60% of left-handed individuals are left-hemisphere dominant, and the two hemispheres contribute differently to cognitive processing, so that injury to a given hemisphere may produce a characteristic cognitive profile [9]. Although these observations are clinically intuitive, the evidence linking hemispheric lesion laterality to cognitive outcome is heterogeneous, and the extent to which laterality adds information beyond lesion volume, strategic lesion location, and the method of cognitive assessment remains debated. This narrative review therefore summarizes the neuroanatomical and pathophysiological basis of post-stroke cognitive impairment, examines the evidence on the relationship between hemispheric lesion location and domain-specific cognitive deficits in the acute phase of stroke, and discusses the implications for early cognitive assessment, prognostication, and rehabilitation planning.

METHODS

This article is a narrative review. Relevant literature was identified through searches of PubMed/MEDLINE, Google Scholar, and the Garuda portal for articles published in English or Indonesian between 2014 and 2025, using combinations of the keywords acute stroke, post-stroke cognitive impairment, vascular cognitive impairment, cerebral hemisphere, lateralization, lesion location, and lesion–symptom mapping. Original studies, systematic reviews and pooled analyses, scientific statements, and authoritative reference texts addressing the anatomy of the cerebral hemispheres, the pathophysiology of post-stroke cognitive impairment, cognitive assessment, and the relationship between lesion location and cognitive outcome were considered. The reference lists of retrieved articles were screened to identify additional relevant publications. The evidence was synthesized qualitatively, and the review was structured according to the criteria of the Scale for the Assessment of Narrative Review Articles (SANRA).

DISCUSSION

Anatomy of the Cerebral Hemispheres

The human brain comprises three principal components: the cerebrum, the cerebellum, and the brainstem. The cerebrum, the largest of these, integrates somatosensory input and governs voluntary movement, language, cognition, memory, emotional regulation, and auditory and visual processing. It is divided into left and right hemispheres, which are separated by the longitudinal fissure but interconnected by the commissural fibers of the corpus callosum [10]. Despite continuous interhemispheric communication, each hemisphere shows functional specialization, or lateralization: the left hemisphere is generally more involved in language, logical reasoning, and mathematical processing, whereas the right hemisphere is more closely associated with creative and artistic functions, music appreciation, and intuition [11].

Each hemisphere consists of an outer cortical layer of gray matter and an inner core of subcortical white matter. Gray matter contains neuronal cell bodies, dendrites, glial cells, and capillary networks responsible for information processing and cognitive activity, whereas white matter consists of myelinated axons that transmit impulses between brain regions [12]. The cerebral cortex is divided into frontal, parietal, temporal, and occipital lobes. Subcortical structures, including the thalamus, basal ganglia, hippocampus, amygdala, and nucleus accumbens, account for approximately one quarter of total brain volume and contribute to cognition, emotional regulation, motivation, and reward processing [13].

Stroke: Definition, Pathophysiology, and Clinical Features

Stroke is a clinical syndrome characterized by the sudden onset of focal or global neurological deficits caused by disturbed cerebral blood flow. It is classified as ischemic stroke, resulting from vascular occlusion and reduced tissue perfusion, or hemorrhagic stroke, resulting from vessel rupture with intracerebral or subarachnoid bleeding [14]. In the acute phase, hypoperfusion triggers an ischemic cascade of energy failure, reduced adenosine triphosphate production, neuronal membrane depolarization, excessive glutamate release, inflammation, and oxidative stress that culminates in neuronal injury and death. The extent of tissue damage depends on the duration of ischemia, the adequacy of collateral circulation, and the timeliness of treatment [15].

Risk factors include non-modifiable determinants such as age, sex, and genetic predisposition, and modifiable factors, foremost hypertension, together with diabetes mellitus, dyslipidemia, heart disease, smoking, obesity, and physical inactivity [16]. Initial clinical assessment relies on the history and on recognition of acute focal neurological signs, including unilateral weakness or sensory loss, facial palsy, speech disturbance, visual disturbance, imbalance, nausea, and sudden severe headache without an obvious cause [17,18]. Post-stroke cognitive impairment occurs irrespective of stroke etiology, may involve one or several cognitive domains, and substantially reduces quality of life [19]. More than 70% of patients exhibit cognitive impairment in the first weeks after onset; most improve within the first three to six months, and spontaneous recovery after the acute phase has been reported in approximately 30% of patients [20,21].

Cognitive Function and Its Assessment

Cognition encompasses the mental processes through which information is acquired, processed, and used, spanning attention, memory, language, executive function, reasoning, and decision-making [22]. Cognitive dysfunction is defined as a significant decline in these abilities that interferes with daily activities and independence [23]. If inadequately managed, chronic cognitive decline can restrict daily functioning and increase the risk of severe cognitive impairment and dementia [24]. Dementia is generally preceded by a transitional stage of MCI, which may arise from neurodegenerative or vascular processes; at this stage, functional dependence is not yet substantial, but progression to dementia may occur within approximately five to six years [25].

The severity of cognitive impairment depends on age, genetic predisposition, education, psychological status, and general health, including cardiovascular and metabolic disease [26]. In clinical practice, cognition is commonly screened with validated instruments such as the Mini-Mental State Examination (MMSE) and the Indonesian version of the Montreal Cognitive Assessment (MoCA-Ina) [27]. In Indonesian post-stroke patients, the MoCA-Ina detected MCI in 72.41% of cases, compared with 31.03% for the MMSE. This difference has been attributed to the broader domain coverage of the MoCA, which includes executive function, naming, memory, attention, language, abstraction, delayed recall, visuospatial ability, and orientation, enabling detection of deficits that the MMSE may miss [28].

Determinants of Cognitive Impairment

Cognitive decline may originate early in life or be precipitated by brain injury, neurological disease, or psychiatric conditions, and it is most frequent in older adults as part of physiological aging. Early-life risk factors include chromosomal or genetic syndromes, prenatal drug exposure, nutritional deficiency, heavy-metal poisoning, pathological neonatal jaundice, and hypoxia; in later life, stroke, delirium, dementia, depression, and chronic disease act as triggers [23]. Chronic pain may also contribute through reduced hippocampal neurogenesis, decreased expression of brain-derived neurotrophic factor (BDNF), and alterations in cytokines, glial cells, enzymes, and neurotrophic factors, predominantly affecting long-term memory, attention, and executive function [25].

Aging is associated with non-uniform volume loss, particularly in the prefrontal cortex, temporal lobes, and hippocampus, resulting in memory decline and slower processing speed [29]. Genetic factors also contribute: the apolipoprotein E ε4 (APOE ε4) allele is a recognized susceptibility gene for cognitive impairment, although it is not deterministic [30]. Lower educational attainment is associated with greater risk, whereas higher education is thought to build cognitive reserve through neuroplasticity, as learning continuously stimulates neuronal development and adaptation [28,31]. Chronic stress, anxiety, and depression impair cognition through elevated cortisol levels and neurobiological changes in the hippocampus, a structure critical for memory and attention [32]. Vascular and metabolic factors are major determinants of cognitive decline. Hypertension, diabetes mellitus, dyslipidemia, obesity, cardiovascular disease, and chronic kidney disease promote blood–brain barrier dysfunction, reduced cerebral perfusion, and neuronal injury [31]. Increased carotid intima–media thickness (CIMT), a marker of this vascular burden, has been significantly associated with cognitive decline and has been proposed as a predictor of cognitive impairment in older adults [33]. Traumatic brain injury, central nervous system infection, and brain tumors may impair cognition through direct tissue damage, inflammation, and disrupted neuronal connectivity [34], while neurodegenerative and psychiatric disorders such as Parkinson’s disease and schizophrenia act through neurodegeneration, neurotransmitter dysfunction, and disruption of cortical and subcortical networks [35,36].

Pathophysiology of Post-Stroke Cognitive Impairment

Post-stroke cognitive impairment reflects damage to both gray and white matter and loss of the integrity of cortical and subcortical structures [23]. In ischemic stroke, reduced oxygen and glucose delivery triggers oxidative stress, mitochondrial dysfunction, excitotoxicity, and sustained neuroinflammation, aggravated by blood–brain barrier disruption that allows the accumulation of neurotoxic proteins and accelerates neuronal death [37]. Reduced cerebral blood flow leads to chronic hypoperfusion that further damages brain tissue, worsens vascular dysfunction, and activates local and systemic inflammation; elevated high-sensitivity C-reactive protein (hs-CRP), for example, correlates significantly with changes in cognitive scores during the acute phase of ischemic stroke [38].

Hypertension, diabetes mellitus, and atherosclerosis contribute through endothelial dysfunction and chronic cerebral hypoperfusion, leading to white matter lesions, microinfarcts, and small vessel disease. Axonal injury and demyelination within the white matter disrupt interneuronal connectivity and impair executive function, memory, attention, and processing speed. Stroke may also trigger neurodegenerative processes involving the accumulation of amyloid-β and tau, together with imbalance of neurotransmitter systems, particularly acetylcholine. Combined with secondary complications such as seizures, these mechanisms jointly drive cognitive decline after stroke [39].

Hemispheric Lesion Location and Cognitive Function

Stroke-related injury affects not only neurons but also neuroanatomical networks and the cerebral microvasculature. Damage to key cognitive structures such as the hippocampus and white matter tracts impairs the integration of information across brain regions, while small vessel injury, including cerebral microbleeds, compromises microperfusion and tissue integrity. Within this framework, hemispheric involvement is an important determinant of the pattern of cognitive impairment in acute stroke. Left hemisphere lesions carry a higher risk of cognitive impairment than right hemisphere lesions, consistent with the dominant role of the left hemisphere in verbal and linguistic processing, and therefore particularly affect verbal memory, executive function, and language [40]. Conversely, the right hemisphere is primarily involved in non-verbal processing, visuospatial ability, and emotional and social cognition. Patients with right hemispheric stroke frequently present with hemispatial neglect, constructional apraxia, anosognosia, and executive and visuospatial dysfunction, deficits that are associated with poorer rehabilitation outcomes, reduced independence in activities of daily living, and greater long-term dependency [41].

Using voxel-based lesion–symptom mapping (VLSM), Sagnier et al. demonstrated that lesion topography determines the pattern of cognitive impairment and predicts cognitive outcome across multiple domains. Left hemisphere involvement predominated across most domains, particularly language and memory, whereas right hemisphere damage was more often linked to visuospatial deficits; executive function, attention, and orientation relied on bilateral networks and were most affected in patients with extensive or bilateral lesions [42]. Domain-level lesion–symptom mapping of the MoCA has further linked visuospatial and executive performance to right temporoparietal and occipital networks; language and naming to left frontotemporal and insular regions, including the inferior frontal gyrus, insula, and angular gyrus; attention to distributed frontal and parietal cortices and the associative visual cortex; abstraction to the left inferior frontal gyrus pars opercularis and left temporopolar region; delayed recall to episodic memory networks involving the parahippocampus, thalamus, and left prefrontal cortex; and orientation to the integration of limbic structures, such as the hippocampus, with frontal and visual cortices [42,43]. These associations are summarized in Table 1.

Table 1. Cognitive Domains and Their Predominant Lesion Locations in Stroke

Note : Hemispheric predominance reflects the balance of evidence; most domains depend on distributed bilateral networks, and strategic lesion location and volume modify these associations.

Ischemic lesions in the left dorsolateral prefrontal cortex, hippocampus, and frontal insula are associated with disrupted neural connectivity and impairment of executive function, attention, and memory [44]. In a multivariate lesion–symptom mapping study of patients with acute ischemic stroke, Zhao et al. showed that post-stroke cognitive impairment is determined not merely by lesion size but primarily by functionally strategic locations: infarcts in the left angular gyrus, left basal ganglia, and adjacent subcortical white matter were significantly associated with global cognitive impairment. These regions belong to frontoparietal and subcortical networks that support executive function, attention, memory, and language. The findings support the concept of strategic infarction, whereby small lesions in critical locations produce disproportionate cognitive effects, and indicate that left hemispheric lesions tend to cause more severe impairment than right hemispheric lesions [45]. Laterality differences may also reflect neurobiological mechanisms beyond functional anatomy, notably the serotonergic system. Serotonin (5-hydroxytryptamine, 5-HT), which is widely distributed in the hippocampus and prefrontal cortex, modulates memory, attention, and other cognitive functions [46]. Post-stroke cognitive impairment is thought to be partly mediated by changes in serotonergic receptor activity after tissue injury. Experimental studies have demonstrated hemispheric asymmetry in serotonin S2 receptor activity, measured by cortical N-methylspiperone (NMSP) binding: binding remains relatively unchanged after left hemisphere lesions but increases after right hemisphere lesions, reflecting receptor activation in viable tissue. This response is regarded as a neuroprotective compensatory mechanism that helps maintain synaptic transmission and cognition, and its relative absence after left hemisphere lesions may contribute to the higher frequency and severity of language, memory, and executive impairment [47].

Beyond Laterality: Strategic Location, Vascular Burden, and Assessment Bias

Although the studies above support an association between left hemisphere involvement and more severe cognitive impairment, hemispheric side alone is an incomplete descriptor of lesion impact. In a pooled analysis of individual patient data from 12 acute ischemic stroke cohorts, Weaver et al. identified strategic infarct locations, most consistently in the left frontotemporal lobes, left thalamus, and right parietal lobe, that were associated with post-stroke cognitive impairment independently of infarct volume [48]. The inclusion of a right parietal region among these strategic locations indicates that right hemisphere lesions can also carry a substantial cognitive burden, particularly in visuospatial and attentional domains.

The cognitive consequences of a new infarct are further modified by the background state of the brain. The prevalence and risk factor profile of post-stroke cognitive impairment differ across ethnoregional groups [49], and pre-existing cerebral small vessel disease, white matter hyperintensities, and neurodegenerative pathology lower the threshold at which an acute lesion becomes clinically manifest [37]. The cognitive impact of small vessel lesions likewise depends on their location within strategic white matter tracts rather than on lesion burden alone [50]. These observations support a network-based model in which laterality, strategic location, lesion volume, and vascular burden act together. Methodological factors also complicate the interpretation of laterality effects. Commonly used screening instruments, including the MMSE and MoCA, rely heavily on verbal comprehension and expression, so that patients with left hemisphere lesions and aphasia may be classified as more severely impaired, whereas visuospatial deficits and neglect after right hemisphere lesions may be under-detected [5]. Anosognosia after right hemispheric stroke may further reduce the reporting of cognitive complaints [41]. Differences in the timing of assessment, stroke subtype, imaging modality, and definition of lesion side across studies contribute to the heterogeneity of reported findings [42].

Clinical Implications

From a practical perspective, hemispheric lesion location can guide, but should not replace, systematic cognitive assessment. Cognitive screening should be performed early in all patients with acute stroke, with the MoCA-Ina offering greater sensitivity than the MMSE in Indonesian post-stroke populations [28]. In patients with left hemisphere lesions and aphasia, test results should be interpreted cautiously and supplemented with assessment tools less dependent on language, whereas patients with right hemisphere lesions warrant specific evaluation of neglect, visuospatial function, and awareness of deficits [41,43]. Integrating lesion location with stroke severity [8] and vascular risk profile allows more accurate prognostication, and domain-specific deficits identified early can inform targeted cognitive rehabilitation, including emerging approaches such as non-invasive brain stimulation [21].

Limitations and Future Directions

This review has several limitations. As a narrative review, it did not apply a systematic search with predefined eligibility criteria or a formal risk-of-bias assessment, and the selection of literature may therefore be subject to bias. The included studies were heterogeneous in design, sample size, stroke subtype, timing of cognitive assessment, and cognitive instruments, which precluded quantitative synthesis. Several Indonesian studies were small, single-center investigations. Future research should include prospective multicenter cohorts in Indonesian populations, using standardized imaging, validated domain-specific cognitive instruments administered at defined time points, adjustment for lesion volume and small vessel disease, and lesion–symptom mapping approaches.

CONCLUSION

Cognitive impairment is a frequent consequence of acute stroke, resulting from disrupted cerebral perfusion and brain tissue injury through ischemia, inflammation, oxidative stress, and network disconnection. The severity and pattern of impairment are influenced by lesion location, particularly hemispheric involvement, through functional brain lateralization. Left hemisphere lesions are more consistently associated with impairment of language, verbal memory, and executive function and with more severe global impairment, whereas right hemisphere lesions predominantly affect non-verbal, visuospatial, and emotional and social functions. However, strategic infarct location, lesion volume, vascular burden, and the verbal bias of screening tools modify this relationship. Early, domain-specific cognitive assessment that takes lesion location into account is therefore recommended to support prognostication and individualized rehabilitation planning after acute stroke.

DECLARATIONS

None

CONSENT FOR PUBLICATION

The Authors agree to be published in the Journal of Society Medicine.

FUNDING

None

COMPETING INTERESTS

The authors declare no conflicts of interest in this case report.

AUTHORS’ CONTRIBUTIONS

T.S conceptualization, literature search, data curation, and writing – original draft. Y.I conceptualization, methodology, supervision, and writing – review and editing. Both authors read and approved the final manuscript.

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ACKNOWLEDGMENTS

The authors express their sincere gratitude to all individuals and institutions who provided academic guidance, access to relevant literature, and constructive input that supported the completion of this review.

REFERENCE