Effect of deep brain stimulation on patients with Parkinson’s disease with mild cognitive impairment

Abstract

Background

Cognitive deficits are prevalent in Parkinson’s disease (PD), often progressing to PD dementia (PDD). Deep brain stimulation (DBS) is an established treatment for PD motor symptoms, but its effects on patients with mild cognitive impairment (PD-MCI) remain unclear. While MCI is a relative contraindication for DBS, evidence regarding its impact on post-operative outcomes is limited. This systematic review aims to assess the post-operative cognitive and functional outcomes of DBS in patients with PD and MCI.

Methods

A comprehensive literature search was conducted across PubMed, Scopus, PsycInfo and Embase following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies published by February 2024 that evaluated DBS outcomes in patients with PD-MCI were included. Data extraction focused on cognitive assessments, quality of life and clinical outcomes.

Results

Eight studies comprising 984 patients met inclusion criteria. Six studies identified PD-MCI as a potential risk factor for developing PDD post-DBS, though only two demonstrated statistically significant cognitive decline post-DBS. Five studies found no differences in outcomes post-DBS, between patients with PD-MCI and PD without cognitive impairment.

Conclusions

DBS does not appear to significantly worsen cognitive decline in patients with PD-MCI beyond the expected disease progression. However, certain cognitive domains, particularly visuospatial impairments, may increase the risk of adverse outcomes. Standardised cognitive screening is necessary for optimal patient selection for future research to refine clinical guidelines for DBS eligibility.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• Mild cognitive impairment (MCI) is common in Parkinson’s disease (PD) and raises concern about cognitive outcomes after deep brain stimulation (DBS), but prior studies are inconsistent due to variable MCI definitions.

WHAT THIS STUDY ADDS

• In a review of eight studies with 984 patients, most with PD-MCI did not show significant postoperative decline, though heterogeneity in MCI criteria limits interpretation.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• Preoperative MCI should not automatically preclude DBS, and standardised MCI definitions are needed to refine patient selection and guide future studies.

Background

Deficits in cognition are common as Parkinson’s disease (PD) progresses. Studies report that cognitive deficits in patients with PD are prevalent and most patients with PD will develop PD dementia (PDD).¹ Cognitive impairment in PD has various presentations including differences in its symptoms, progression and severity. These range from mild cognitive impairment (PD-MCI) to severe deficits as in PDD.² The Movement Disorder Society (MDS) Task Force defines PD-MCI as a clinical syndrome characterised by a gradual cognitive decline in individuals with established PD, documented by subjective report or clinical observation and confirmed by objective cognitive impairment on testing, while functional independence is largely preserved and criteria for PDD are not met. The Task Force further operationalises PD-MCI using a two-level diagnostic framework, consisting of Level I (abbreviated assessment using global cognitive scales or limited testing) and Level II (comprehensive neuropsychological evaluation with impairment on at least two tests across one or more cognitive domains).³ Despite its variable presentation, these patients endure a significant impact on functioning, increased nursing home admissions, psychiatric morbidity, caregiver burden and mortality.^{1 4}

MCI in patients with PD is important to identify as it has been associated with higher rates of developing dementia in the future with a rate of annual progression between 6% and 15%.⁵ MCI leads to a decline in functioning from baseline but is not severe enough to significantly interfere with activities of daily living like PDD. Many neuropsychological scales are used for the diagnosis of cognitive impairment in the setting of PD. Some of these scales include Montreal Cognitive Assessment (MoCA) and Mini-Mental Status Examination (MMSE).^{4 6} Early studies described PD-MCI subtypes as amnestic, single non-memory domain and multiple-domain impairment, whereas the MDS Task Force later standardised PD-MCI subtyping into single-domain and multiple-domain categories based on comprehensive neuropsychological assessment.^{4 7 8}

Deep brain stimulation (DBS) is offered to patients whose symptoms remain refractory to pharmacological therapy. Despite the success of DBS in treating motor symptoms of PD, cognitive impairment remains a relative contraindication for patients due to ethical concerns and potential adverse outcomes.⁹ Although cognitive deficits remain a contraindication, the outcome of DBS in patients with PD-MCI remains unclear. Little empirical literature is available where specifically the impact of DBS outcomes on patients with PD-MCI is studied.^{5 10}

Some studies have shown that the rate of dementia remains similar in patients that were medically treated and those who received DBS,^{11 12} while other studies suggest that specific cognitive impairments may be associated with a variety of poorer outcomes including confusion, length of hospitalisation and faster rate of cognitive decline after DBS.^{12 13} Literature suggests that MCI has not been associated with poorer outcomes or dementia risk other than that expected on the basis of the natural disease course but persists as a relative contraindication for many providers.⁵

Despite a lack of evidence for adverse outcomes related to DBS in patients with MCI, due to the high prevalence of MCI in patients with PD, many are potentially excluded from receiving the quality-of-life improvement possible with DBS implantation. This systematic review aims to consolidate evidence about post-operative adverse effects of DBS on patients with PD-MCI, hoping to inform guidelines for providers to provide DBS as a therapeutic option to their patients.

Methods

A comprehensive search across PubMed, Scopus, PsycInfo and Embase databases was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medical Subject Headings and keyword terms were combined to create individualised search queries adapted appropriately to each database. Independent extraction by three authors was performed using the web application Rayyan to determine eligibility under blind review.

Search method

This systematic review was conducted according to guidelines from the (‘Preferred Reporting Items for Systematic Reviews (and Meta-Analysis statement)’)¹⁴ and the Cochrane Handbook for Systematic Reviews.¹⁵ An electronic search of the National Library of Medicine (PubMed), Scopus and Embase was performed for articles published before February 2024. The search strategy was generated and the search terms used are shown in table 1. This review was not registered in a review registry (eg, PROSPERO).

Table 1. Database search strategy and specific queries used to identify eligible studies.

Database	Specific query used for search	Number of results
PubMed	(“deep brain stimulation”(MeSH Terms])OR (“deep”(All Fields])AND “brain”(All Fields])AND “stimulation”(All Fields)) OR “deep brain stimulation”(All Fields)) AND (“cognitive dysfunction”(MeSH Terms])OR (“cognitive”(All Fields])AND “dysfunction”(All Fields)) OR “cognitive dysfunction”(All Fields])OR (“mild”(All Fields])AND “cognitive”(All Fields])AND “impairment”(All Fields)) OR “mild cognitive impairment”(All Fields)) AND “parkinson*"(All Fields)	202
Scopus	(TITLE-ABS-KEY (deep AND brain AND stimulation OR dbs) AND TITLE-ABS-KEY (parkinson*) AND TITLE-ABS-KEY (mild AND cognitive AND impairment))	81
PsycInfo	(deep brain stimulation or dbs) AND parkinson* AND (mild cognitive impairment or mci)	18
Embase	deep brain stimulation AND (parkinson*) AND ('mild cognitive impairment’)	105
Other		6

Three authors (SHV, PD and PR) independently reviewed the search entries using strict inclusion and exclusion criteria defined below. After removing duplicates, articles were first screened by title and abstract using the web application Rayyan to determine eligibility under blind review, followed by a full-text review. Discrepancies between reviewers were noted through the Rayyan system and subsequently rereviewed and resolved by consensus. A total of 345 articles were screened after removal of duplicates and six additional studies that did not appear in the search. Ultimately, after a thorough screen and consensus among reviewers, a total of eight studies were analysed in the systematic review.

Inclusion/exclusion criteria

Original science studies with preoperative diagnosis of PD-MCI and measurement of a specific outcome after DBS implantation surgery were included. Case reports, non-sequential patient series, studies in languages other than English and studies only reported in abstract form were excluded to reduce selection bias within studies. Review articles such as systematic reviews, meta-analyses, narrative reviews and scoping reviews were also excluded. Original science studies with no DBS implantation, no preoperative diagnosis of PD-MCI, wrong study design, not assessing DBS outcomes and animal studies were excluded from the study. Figure 1 shows the PRISMA flowchart of the study.

Figure 1. Total articles screened (PRISMA flow chart). PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Data extraction

A variety of variables were systematically extracted based on the study design and the outcomes measured in the research. Demographic information, including age, number of patients, preoperative prevalence of MCI, subtype of MCI and mean disease duration, was extracted. Additionally, whether any quality-of-life measurement was used was also included. Characteristics related to DBS surgery, such as laterality and target nucleus, were recorded. A range of clinical assessments related to PD outcomes was recorded: Levodopa Equivalent Daily Dose (LEDD), Unified Parkinson’s Disease Rating Scale scores and various cognitive evaluations. These cognitive assessments included the MMSE, MoCA, as well as specific tests focused on language, recall, attention, memory and visuospatial learning. Detailed information on the data collected is presented in table 2, which outlines the outcomes measured in each study. Online supplemental table 1 offers a brief description of the tests and scales used for the outcomes. Table 3 summarises the demographic data for each study.

Table 2. Neuropsychological tests and clinical outcomes measured in each included study.

Author	Year	MCI measure	Single/multidomain MCI	Outcomes measured
Yaguez et al	2014	WAIS III	Multidomain	General intellect: verbal IQ, performance IQ, full scale IQ Memory functions: immediate story recall, delayed story recall, list learning, verbal recognition, visual recognition Language functions: Graded Naming Test Perceptual functions: incomplete letters, object decision Executive functions: Hayling Sentence Test, Brixton Test, verbal fluency
Gruber et al	2019	MDDS	Single domain	Global cognition: mMDRS total, mMDRS memory, MDRS attention, MDRS initiation, MDRS construction, MDRS conception Short- and long-term memory: RAVLT immediate recall, RAVLT free recall, RAVLT delayed recall, RAVLT recognition Executive function: TMT B: errors, TMT B–A (s), Stroop interference (s) Working memory: Digit span forward Digit span backward Attention: Trail Making A (s) Stroop words (s) Stroop colours (s) Affect: BDI, MADRS, MDMQ total score, ‘Well-being’, ‘Activation’, ‘Nervosity’, BAI, BRMAS, BPRS, SHAPS-D Quality of life: PDQ 39, SF 36
Abboud et al	2015	Global Cognition Score	Multidomain	Immediate DBS surgical outcomes: length of postoperative hospitalisation, occurrence of postoperative confusion Intermediate outcomes: 6 months postoperative MDS-UPDRS II, EQ5D Long-term outcomes: 1-year postoperative MDS-UPDRS II and EQ5D
Merola et al	2014	Global Cognition Score	Multidomain	Memory functions: PAL, CBT Language: phonemic verbal fluency, category verbal fluency Perceptual: Raven’s CPM, Block Design Executive: TMT-B
Kim et al	2014	Global Cognition Score	Multidomain	Memory functions: Immediate recall, Delayed recall, Recognition, RCFT Language: K-BNT, phonemic fluency, semantic fluency Executive: TMT-B, TMT-C, Stroop Test Attention: TMT-A Affect: BDI Motor Function: UPDRS (on/off), LEDD
Block et al	2023	Global Cognition Score	Multidomain	Attention: WAIS-IV Digit Span subtest—forward span, TMT-A, DRS-2 Attention Index Executive function: TMT-B, Wisconsin Card Sorting Test Total Categories, DRS-2 Conceptualisation Index Language: Boston Naming Test-2 Total Score, WAIS-IV Vocabulary subtest, WASI-II Vocabulary subtest Memory: RAVLT, RAVLT Delayed Free Recall, HVLT-R, HVLT-R Delayed Free Recall, WMS-IV Logical Memory WMS-IV Logical Memory II, DRS-2 Memory Index Visuospatial: Judgement Of Line Orientation Total corrected score (percentile), WAIS-IV Block Design subtest (scaled score), WASI-II Block Design subtest, DRS-2 Construction Index Fluency: Semantic fluency—animals, COWAT—FAS (T-score).
Xie et al	2022	MOCA	Multidomain	Global cognitive function: MMSE, MoCA, MoCA specific Motor function: Levodopa responsiveness
Park et al	2020	Seoul Neuropsychological screening battery	Multidomain	DBS surgical outcomes: mortality, nursing home admission, progression to Hoehn and Yahr stage 5 and progression to PDD Multiple cognitive domain: attention, executive function, memory, language, visuospatial

BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; BRMAS, Bech-Rafaelsen Mania Scale; CBT, cognitive–behavioural therapy; COWAT-FAS, Controlled Oral Word Association Test- Letters F, A or S; CPM, Coloured Progressive Matrices; DBS, deep brain stimulation; DRS-2, Dementia Rating Scale-2; EQ5D, EuroQol-5 Dimension Scale; HVLT-R, Hopkins Verbal Learning Test-Revised; K-BNT, Korean version of the Boston Naming Test; LEDD, Levodopa Equivalent Daily Dose; MADRS, Montgomery-Åsberg Depression Rating Scale; MCI, mild cognitive impairment; MDDS, Mild Dementia Daily Symptom Scale; MDMQ, Multidimensional Mood Questionnaire; MDRS, Mattis Dementia Rating Scale; MDS-UPDRS, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale; mMDRS, Modified Mattis Dementia Rating Scale; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment; PAL, Paired Associate Learning; PDD, Parkinson’s disease dementia; PDQ-39, Parkinson’s Disease Questionnaire-39; RAVLT, Rey Auditory Verbal Learning Test; RCFT, Rey Complex Figure Test; SF-36, Short Form-36 Health Survey; SHAPS-D, Snaith-Hamilton Pleasure Scale-Depression; TMT-A, Trail Making Test Part A; TMT-B, Trail Making Test Part B; TMT-C, Trail Making Test Part C; UPDRS, Unified Parkinson’s Disease Rating Scale; WAIS III, Wechsler Adult Intelligence Scale-III,; WAIS-IV, Wechsler Adult Intelligence Scale-IV; WASI-II, Wechsler Abbreviated Scale of Intelligence-II; WMS-IV, Wechsler Memory Scale-IV.

Table 3. Demographic and clinical characteristics of patients included across studies.

Author	Mean age (SD)	Sample size	Gender (M/F)	Preoperative diagnosis of MCI (%)	Disease duration (years SD)	DBS target	Follow-up (months)	Bilateral/unilateral
Yaguez et al	58±7.3	30	15/15	46.7	11.4±5.3	STN	6
Gruber et al	61.8±7.0	37	NA	75.7	11.3±4.2	STN	12	Bilateral
Abboud et al	63 (± 9.1)	130	92/38	80.8	10.7 (±5.1)	N/A	12	Both
Merola et al	60.31 (±6.7)	174	104/70	23	13.91 (±4.75)	STN	12
Kim et al	56.9 (±7.8)	103	46/57	63	10.6 (±4.5)	STN	12	Bilateral
Block et al	64.8 (±9.0)	80	68/12	50	11.4 (±5.2)	STN GPi ViM		Both
Xie et al	62.42 (±8.5)	126	72/54	61.9	9.41 (± 4)	STN	36
Park et al	60.9 (NA)	304	NA	69.1	13.14 (NA)	STN/GPi	12
Overall	61.02 (±7.5)	984	M=397/643=61.7% F=246/643=38.3%	58.8	11.48 (±4.4)

.DBS, deep brain stimulation; GPi, globus pallidus internus; MCI, mild cognitive impairment; NA, not assessed; STN, subthalamic nucleus; ViM, ventral intermediate nucleus.

ROBINS-I criteria

The risk of bias in the included studies was evaluated using the ROBINS-I tool (Risk of Bias in Non-Randomised Studies–of Interventions), developed by Cochrane. This tool assesses seven domains: confounding, classification of interventions, selection of participants, deviations from intended interventions, missing data, measurement of outcomes and selection of the reported result. Each domain was rated as having a low, moderate, serious or critical risk of bias.¹⁶ A summary of these assessments is provided in online supplemental table 2, in accordance with the ROBINS-I guidelines.

Data synthesis

The authors originally wished to attempt to pool the data for further analysis, but this was not possible due to the heterogeneity of the tests and the definitions of MCI that were employed across the studies included in the review. Therefore, the authors decided to show the various definitions that are used across the studies and the need for a standardised definition of MCI to further parse out the impact of cognitive deficits prior to DBS implantation.

Data sharing

This systematic review was conducted using Rayyan.ai (https://new.rayyan.ai/). The data supporting the findings of this systematic review are available from the corresponding author on reasonable request.

Results

In the eight studies included, the measurement of MCI varied, with four studies employing the Global Cognition Score as the primary method. All included studies were observational in design. Among these, only Yágüez et al and Kim et al^{17 18} employed a prospective study design, whereas all remaining studies were retrospective observational analyses.

Patient demographics

A total of 984 patients participated in the eight studies included in this systematic review. The mean patient age was 61.02 (±7.5) years, with 61.7% of patients being male. The prevalence of preoperative MCI ranged from 23.0% to 80.8% resulting in an overall average prevalence of approximately 58.8%. This value should be interpreted descriptively rather than as a pooled estimate, given heterogeneity in MCI definitions. The mean disease duration ranged from 9.41 years to 13.91 years, resulting in an overall mean duration of 11.48 (± 4.4) years. Four studies compared cohorts of patients with PD and MCI (PD-MCI) and those without MCI (PD-NC), matching patients across similar baseline characteristics including age, LEDD and mean disease duration. Seven of the eight studies examined patients receiving DBS targeting the subthalamic nucleus (STN), while other targets included the globus pallidus interna (GPi) and the ventral intermediate nucleus (ViM/VIM). Gruber et al¹⁹ were the only study to include patients with single-domain MCI, while all other studies included patients with multidomain MCI. Further demographic details regarding the patient population are available in table 3.

Postoperative outcomes

Six of the eight studies reviewed identified pre-existing MCI as a potential risk factor for developing PDD following DBS implantation. A higher proportion of patients with PD-MCI was observed to progress to PDD compared with those without cognitive impairment (PD-NC); however, only two out of the eight studies demonstrated a statistically significant impact of preoperative MCI diagnosis on postoperative outcomes. Kim et al¹⁷ concluded that patients with MCI are at a higher rate of converting to PDD, but due to the lack of a control group, they were unable to differentiate between the natural progression of the disease or the effect of DBS on the disease process. Yaguez et al¹⁸ state that there was a decline in memory tests with all cohorts postoperatively, but the MCI cohort had an additional decline in verbal memory. Five of the studies showed no differences in outcomes from DBS surgery in PD-MCI and PD-NC. Abboud et al²⁰ showed no difference in quality of life or functional outcomes between the cohorts, while Block et al showed there was no difference in adverse events. Although outcome measures varied across studies, a comprehensive summary of the outcomes evaluated and their results is provided in table 4, while the specific outcome instruments used in each study are summarised in table 2.

Table 4. Summary of key findings and conclusions from the included studies.

Author	Preoperative MCI associated with any outcomes	Changes in population	Correlation of Pre-OP conditions	PO changes	Special notes
Yaguez et al	Yes	Increase from Pre-OP 46.7% to PO 63.3%. MCI.	No correlation for age, mean disease duration and UPDRS scores. Pre-OP FSIQ and List Learning are best predictors of decline in story recall PO. STN DBS does not affect pre-existing frontal executive dysfunction.	Mild decline in verbal memory suggesting temporal function more sensitive to decline in patients with MCI. Three memory tests with statistical significance all group decline PO.
Gruber et al	N/A	Pre-OP 76% MCI, 24% NC to PO 41%. Dementia, 41% MCI and 18% NC.	No correlation of age, mean disease duration, LED, motor function, Levodopa response.	The trend of association between preoperative MCI and conversion to dementia was noted but not statistically significant.	The study lacks comparison of PD-NC against patients with PD-MCI.
Abboud et al	No		Visuospatial dysfunction predicts less favourable intermediate and long-term outcomes following DBS.	Presence of MCI did not affect DBS outcomes. Executive dysfunction, the most common cognitive impairment in PD, did not affect PO functional or QoL outcomes.	PD-MCI definition was only 1 SD below age expectation of neuropsychological tests.
Merola et al	No	Significant difference between development of dementia of MCI versus NC.	Gender, age at the disease onset, age at surgery and LEDD were similar in PD-MCI and normal cognition patients.	No different neuropsychological outcomes were observed after the first year of surgery. DBS does not worsen pre-op MCI. Phonemic verbal fluency was worsened in NC patients.
Kim et al	Yes	Patients with MCI at a higher risk of converting to PDD.	Poor executive function and impaired attention were risk factors for faster global cognitive decline and dementia.	Preoperative PD-MCI was a risk factor for dementia after STN DBS.	PD-MCI definition was only 1 SD below age expectation of neuropsychological tests.
Block et al	No		Patients with moderate cognitive impairment with lower baseline DRS-2 score and higher UPDRS 1, UPDRS 2, UPDRS 3 off med than PD-NC.	No differences in clinical outcomes based on impairment in a specific cognitive domain There were also no differences in adverse events.	PD-Moderate cognitive impairment definition was 2 SD below age expectation of neuropsychological tests.
Xie et al	No	Patients with PD-MCI progressed to PDD in higher proportions than PD-NC individuals.	PD-MCI and PD-NC did not differ significantly in any other baseline characteristics.	Results demonstrate that both groups showed a significant postoperative decline in terms of visuospatial/executive function, attention and language. PD-NC shows more declines in visuospatial/executive function and attention than PD-MCI.
Park et al	No	PD-MCI showed higher HR for progression to HY stage 5 compared with PD-NC.	Visuospatial impairment was predictive of progression of HY stage 5 in patients without dementia.	They found no difference between PD-NC and PD-MCI in their outcomes.

DRS-2, Dementia Rating Scale-2; FSIQ, Full Scale IQ; HY stage 5, Hoehn and Yahr Stage 5; LED, Levodopa Equivalent Dose; LEDD, Levodopa Equivalent Daily Dose; MCI, mild cognitive impairment; N/A, not assessed; NC, normal cognition; PDD, Parkinson’s disease dementia; PD-MCI, Parkinson’s disease with mild cognitive impairment; PD-NC, Parkinson’s disease with normal cognition; PO, postoperative; Pre-OP, preoperative; QoL, Quality of Life; STN DBS, subthalamic nucleus deep brain stimulation; UPDRS, Unified Parkinson’s Disease Rating Scale.

Discussion

This systematic review presents a compilation of evidence indicating that patients with a preoperative diagnosis of MCI do not have worse outcomes following DBS implantation compared with patients without preoperative MCI. The findings of this systematic review have clinical implications on identifying patients who may experience improvements in PD motor symptoms and overall quality of life following DBS implantation. Ethical considerations and practical challenges limit the application of DBS in individuals with cognitive impairment or dementia. Therefore, rigorous screening and careful patient selection are essential, as concerns regarding informed consent, as well as potential declines in quality of life or functional independence, present significant challenges.²¹

Post-DBS management necessitates strict adherence to protocols and medication regimens, which can be especially challenging for patients with advanced cognitive dysfunction.²² According to Abboud et al,²⁰ approximately one-third of patients excluded from DBS consideration were dismissed due to cognitive factors such as dementia or MCI. The literature indicates that the prevalence of MCI among individuals with PD varies from 25% to 50%, depending on the studied population and the definitions of MCI applied.²³

There is limited evidence regarding the impact of a preoperative MCI diagnosis on outcomes following DBS. Of the seven studies that analysed the effect of preoperative MCI in this review, five reported no significant differences in outcomes between cohorts with and without MCI (PD-MCI vs PD-NC). Among the two studies with statistically significant findings, Kim et al¹⁷ identified a higher proportion of patients with PD-MCI progressing to PDD compared with those with PD-NC. This trend was also observed in six other studies, although they attributed the difference to the natural progression of PD rather than the effects of DBS implantation.1920 24,27 While individuals with MCI were noted to experience earlier dementia onset, no cases of early-onset dementia directly attributable to DBS were reported. This is consistent with existing literature suggesting the diagnosis of MCI is in itself an independent risk factor for developing dementia.¹¹ Aybek et al²⁸ found in 2007 that the rate of dementia at 3 years following STN DBS was comparable to that in patients managed with medical therapy alone. These findings suggest that the observed increase in progression from PD-MCI to PDD is more likely due to the natural course of the disease than to DBS surgery itself.

When evaluating the impact of DBS on cognitive outcomes in PD, it is essential to consider factors such as the type of pre-existing cognitive impairments and the specific DBS targets. While an overall diagnosis of MCI may not significantly influence DBS outcomes, certain cognitive domain deficits warrant closer attention. Preoperative visuospatial deficits have been correlated with increased complications in DBS patients. Abboud et al linked them to greater postoperative morbidity including longer hospital length of stay and attentional impairment, while Park et al²⁷ associated them with increased likelihood of nursing-home placement, progression to Hoehn and Yahr stage 5, and subsequent PDD. Collectively, these findings align with broader evidence that posterior-dominant visuospatial impairment confers higher risk of conversion to PDD than anterior/frontal–executive deficits.²⁹ Previous literature has suggested that DBS itself can influence cognitive functions, with STN DBS specifically associated with declines in verbal fluency, attention and memory in any person with PD regardless of preoperative cognitive status.³⁰ Yaguez et al¹⁸ corroborate these findings, noting that while verbal fluency deteriorated in both cohorts, patients with MCI were at a slightly higher risk for such cognitive decline post-DBS.

Of note, Xie et al²⁶ reported greater cognitive decline in the PD-NC cohort compared with the PD-MCI cohort. The authors suggest this discrepancy may be due to the baseline impairments in the PD-MCI group, which could mask further cognitive deterioration. However, Xie et al also highlighted limitations in their study, particularly the exclusive use of the MoCA, which may not comprehensively evaluate cognitive function.

The selection of the DBS target nucleus is an important consideration, particularly in patients with preoperative cognitive impairment. The ViM nucleus is infrequently targeted due to its primary role in tremor management. In the broader PD literature, randomised trials comparing STN and GPi stimulation have demonstrated generally similar overall cognitive outcomes. Where differences have been observed, they are typically small in magnitude, with STN stimulation associated with slightly greater declines in measures of processing speed, working memory, verbal fluency or mood.³¹ Importantly, these effects have generally not translated into clinically meaningful differences at the group level.³² In the present review, no target-specific cognitive signal was identified. Interpretation is limited by the predominance of STN cohorts, as only two included studies enrolled GPi patients (n=124). Block et al found that STN stimulation was associated with greater LEDD reduction than GPi stimulation. However, motor outcomes and adverse event profiles were similar across targets.^{25 27} Collectively, current evidence does not support a clear neuropsychological advantage of one target over the other in PD-MCI, underscoring the importance of individualised target selection based on patient-specific cognitive, behavioural and therapeutic goals.³¹

A significant limitation in the literature on this topic is the inconsistency in the definition of PD-MCI. Variations in diagnostic tests and criteria for assessing MCI severity substantially impact the interpretation of outcomes. Park et al²⁷ demonstrated that different definitions of MCI, such as applying 2.0 SD versus 1.0 SD cut-offs, can alter the perceived risk of disease progression, underscoring the need for standardised and rigorous screening methods. Table 5 shows the definitions of MCI employed by the studies. For instance, Abboud et al and Kim et al relied on impairment in at least two neuropsychological tests with a threshold of ≥1 SD below normative values, while Yágüez et al and Block et al applied more stringent ≥2 SD cut-offs on domain-specific testing. In contrast, Xie et al used education-adjusted cut-offs for screening tools such as the MMSE and MoCA, and Merola et al²⁴ emphasised moderate or severe impairment on multiple tests. These discrepancies illustrate how some studies adopt more lenient definitions, whereas others are stricter in their definitions. Furthermore, the diverse cognitive assessments employed across studies hinder the generalisability of findings. Cultural variation has been shown to affect the validity of neuropsychological assessments, potentially leading to misclassification of MCI in PD.³³ Given the importance of these measures for DBS eligibility, integrating culturally sensitive approaches represents an important area for improving risk stratification in patients with PD and MCI. Formal assessment of publication bias, such as funnel plots or statistical tests for small study effects, was not done because of the limited number of included studies which can make these methods unreliable. Nonetheless, the possibility of bias remains an important consideration and underscores the need for further studies to strengthen the evidence base. Prospective studies using standardised screening and cognitive evaluations will yield more definitive insights into the effect of MCI on DBS outcomes within the PD population.

Table 5. Definitions of MCI applied by each study.

Study	MCI criteria	Framework/threshold
Xie et al	MMSE >20 (1–6 years education) >24 (≥7 years) MoCA >20 (1–6 years education) >24 (≥7 years)	MoCA and MMSE
Yágüez et al	Domain tests listed in table 2	≥2 SD below mean on any cognitive test
Abboud et al	Impairment on ≥2 neuropsychological tests based on MDS Level II criteria	≥1 SD below norms
Block et al	Domain tests listed in table 2	Moderate cognitive impairment = ≥2 test scores ≥2 SD below norms in ≥1 domain (≥2 for memory)
Gruber et al	MDS Level I	≥1 SD below norms
Kim et al	Impairment on ≥2 neuropsychological tests based on MDS Level I criteria	≥1 SD below norms
Merola et al	Impairment on ≥2 neuropsychological tests based on MDS Level I criteria	Moderate or severe impairment on ≥2 neuropsychological tests
Park et al	Impairment on≥2 neuropsychological tests based on MDS Level II criteria	≥1 SD below norms

MCI, mild cognitive impairment; MDS Level I, Movement Disorder Society comprehensive (Level II) neuropsychological battery; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment; MSD II, Movement Disorder Society abbreviated assessment.

This study represents an important step toward extending the benefits of DBS to patients with MCI; however, caution is warranted in generalising these findings. Most included studies focused on STN as the target, limiting this study’s conclusion to other DBS targets. There is also variability in post-DBS care and long-term medical management which is often individualised and was not standardised across studies. This introduces significant confounding that should be addressed in future prospective designs. Additionally, heterogeneity in MCI definitions and neuropsychological assessments also limited the feasibility of a pooled analysis. Surgical targeting, lead placement and stimulation programming can also significantly influence outcomes and were not uniformly accounted for. Many studies had small sample sizes, limiting statistical power. Additionally, the duration of follow-up was often short, typically less than 12 months, which may not be sufficient to capture meaningful cognitive decline in a slowly progressive condition like PD. Another critical factor is the variability and limited sensitivity of cognitive assessments. Several studies relied exclusively on global screening tools such as the MoCA and MMSE, which may not detect subtle or domain-specific cognitive changes, particularly in areas like verbal fluency or visuospatial processing. The ROBINS-I assessment showed most studies had moderate risk of bias, mainly due to confounding and outcome measurement. Abboud et al was the only study rated low risk across all domains. Block et al had critical overall bias, with serious concerns in nearly every domain. Other studies, such as Yágüez et al and Merola et al, had multiple moderate or serious risks, highlighting the need for better control of baseline variables and consistent cognitive assessment methods. Overall, the strength of the evidence remains moderate at best, as conclusions are based on a small and methodologically heterogeneous body of predominantly non-randomised studies, with variability in PD-MCI definitions, cognitive assessment strategies and duration of follow-up. These limitations constrain the generalisability of the findings, but the results provide a foundation for future standardised investigations into the role of DBS in patients with MCI.

Clinical implications

In summary, the findings of this review suggest that a preoperative diagnosis of MCI does not appear to significantly influence DBS outcomes in PD, although heterogeneity in MCI definitions, cognitive assessments, follow-up duration and the moderate-to-serious risk of bias across included studies limits the generalisability of this conclusion. Given the limitations, we refrain from asserting immediate clinical applicability; however, preliminary findings suggest that preoperative evaluation for DBS candidacy should incorporate domain-specific neurocognitive testing rather than relying solely on PD-NC versus PD-MCI categorisation. PD is heterogeneous, and dementia risk depends on factors such as disease duration, baseline cognition, surgical technique, stimulation parameters and comorbidities. Although the outcomes appear to be more closely related to the natural progression of the disease than to the DBS procedure itself, further studies with long-term follow-up are required. While the overall effectiveness of DBS is consistent between patients with PD-MCI and PD-NC, certain domains of cognitive impairment, particularly visuospatial impairments, may be associated with an increased risk of adverse postoperative outcomes and should be carefully integrated into risk stratification during the preoperative evaluation. Future investigations should prioritise the integration of standardised diagnostic criteria and thorough cognitive evaluations to enhance our understanding of the nuanced effects of MCI on DBS outcomes, thus helping refine the patient selection processes.

Effective screening and patient selection processes could enable a greater number of patients to benefit from DBS. Therefore, excluding patients solely based on cognitive dysfunction, as determined by neurologists and neurosurgeons, may prevent many individuals who could otherwise gain from the advantages of DBS stimulation from receiving appropriate treatment due to their preoperative MCI diagnosis.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.