This is a long follow-up cohort of study examing the clinical value of SCD in PD patients and progression characteristics, evaluating rehabilitation training feasibility for SCD in PD patients. We performed a 3-year follow-up investigation with the diagnosis of cognitively normal patients with PD(n = 42). Twenty-two patients were diagnosed with PD-SCD+ (52.4%) at the baseline. Conversion to PD-SCD+ during the follow-up was 54.5% in PD- SCD−, whereas no PD-SCD+ patients revert back to PD-SCD−. There was no patient who is converted to MCI in this study.
There was no current consensus on how to assess SCD. Most studies[23–24] were to use a brief questionnaire, or a simple yes/no question. Only capture subjective cognitive decline for one or two of the five cognitive domains. Given that these patients have been shown to have impairments in other cognitive domains, not just memory. The assessment of SCD in our study is defined based on the SCD research standards proposed by the SCD Advocacy Group in 2014, assessed by five cognitive domains. Interestingly, SCD questions presented limited overlap, we analyzed the assessment of SCD using the Multiple Response Test to make a description. These data(Fig. 1) showed that patients complain with cognitive decline of memory are the most. Baseline comprehensive neuropsychological tests in present study showed that the PD-SCD+ and PD-SCD− groups did not differ significantly, except memory(immediate and delayed recall 2), which was not in agreement with previous report[25]. To date, the assessment of SCD is based largely on overall neuropsychological tests, there are rarely to assess cognitive subsets of SCD. For maximize understanding of SCD, further research need to standardized research, diagnostic criteria and enlarge samples. The concept of subjective “memory” complaint is derived from amnestic MCI as this subtype has been regarded as pre-dementia status[26]. Moreover, deficits in memory, which count among the most sensitive cognitive markers for early recognition of AD[27]. However, there were notable differences between AD-MCI vs PD-MCI[28]. A common cognitive profile has been established for AD-MCI, in which the first and most severe deficits are seen in memory[29], but it has not yet been possible to define such a common cognitive profile for PD-MCI[26]. This means cognitive impairment of PD might be different from AD, patients or their caregivers are often the first or the most worried in the patient's cognitive function may be still memory decline, whereas Iván Galtier[20] showed difficulties in language (60.5%) and memory (51.5%) were the most frequent cognitive complaints. This conclusion was different with our study as may be ascribed to a different assessment of SCD.
A longitudinal analysis of cognitive performance changes showed that patients with PD-SCD+ exhibited a more rapid decline in BJ-MoCA and semantic fluency compared with those without SCD. While the C-MMSE scores were no changes between two groups. To date, there were only three studies[13, 19, 20] conducted a follow-up study to investigate the association between SCD and cognitive impairment in PD patients. No studies have found evidence of overall cognitive function(BJ-MoCA) exhibited a more decline in PD-SCD+ than PD-SCD−, which may due to differential use of comprehensive neuropsychological assessment as cognitive performance was evaluated using the Korean version of Mini-Mental State Examination(K-MMSE) in Hong's study. This result somewhat reiterates that BJ-MoCA is a more sensitive instrument than C-MMSE in detecting cognitive impairment, specifically the cognitive changes associated with the SCD stage. The above result was similar to Hong's study[30], which have found that PD patients with SCD performed significantly worse on semantic fluency(r = 0.40), compared with healthy controls. Language output in PD was often more sparse and less informative than healthy peers[31–33]. Williams and Mason[34] demonstrated in their study that semantic fluency deficits in PD has been identified as a potent risk factor of the development of PD related dementia, with these impairments might reflect the spread of PD pathology to posterior temporal networks. In a word, the present data demonstrated that BJ-MoCA is more sensitive than C-MMSE in detecting cognitive impairment, semantic fluency impairments may represent important cognitive markers to help tracking disease progression and should be key component of the cognitive subsets in assessing PD-SCD.
Language, as a tools of communication, is a higher cortical function and closely related to other cognitive functions. Much of the research capture different sub-domains of language and its progression characteristic over time in PD, this is an ever increasing number of topic. The findings of the present study focused on determining which clinical variables had the greatest ability to differentiate between each cognitive subsets. We evaluated whether the SCD reported by patients with PD at baseline was closely related to each cognitive subsets. The stepwise regression analyses revealed that MMSE scores, HAMD scores, male and the presence of SCD as significant predictors in language domain of PD. Our data showed that cognitive performance in patients with PD may differ based on the presence of SCD, particularly in language function(semantic fluency), suggesting that SCD in patients with PD reflects cognitive-related semantic fluency more closely than PD without SCD. SCD in patients with PD is one of risk factors for cognitive domain of language function[13], which was in agreement with the results of the present study. Ignacio Obesoa[35] found that the non-motor features as well as depression(HAMD) and global cognitive ability(MMSE) influence semantic fluency of PD patients, which was in agreement with the results of the present study. While gender did not affect semantic fluency scores in Obesoa's study, this conclusion was different from our study which may be ascribed to a difference in age, educational level, duration of motor symptom, stage of disease. Yet, relatively little information is available about how key clinical features of PD patients with SCD influence performance on semantic fluency tests. Therefore, the role of sex and the presence of SCD in the predictive value of language function should be clarified more concretely in future studies.
Rehabilitation training has shown benefits in Parkinson's disease in the past decades[36]. There has been relatively few trials of rehabilitation training strategies for SCD in patients with PD. The present study focused on the effects of interventions at the stage of SCD in patients with PD. All participants maintained high levels of effort and most of them had high homework adherence (36 of the 42 participants' complete homework). The results of the present study supported the feasibility of rehabilitation training that could improve cognitive function in terms of BJ-MoCA scores for PD -SCD+ and PD-SCD−. Similar results were reported that the tango dancing for PD patients promoted significant improvement in global cognitive function (MoCA) when compared to the control group who attended lectures only[37], the group of patients is diagnosed with idiopathic PD, compared to our study patients is diagnosed with SCD in patients with PD. C-MMSE and memory scores was found a significant improvement in our PD-SCD− groups. Pairwise comparisons showed that language at post-intervention in the PD-SCD+ groups were significantly higher than at pre-intervention in the PD-SCD−. It is established that different exercises have been found to selectively affect different regions of the brain as physical exercises affect brain plasticity[38]. A meta-analysis of randomized controlled trials(RCTs)[39] showed that aerobic exercise produced improvements in attention, speed, executive function and memory among adults without dementia. Altmann[40] demonstrated that aerobic exercise can positively impact mood and executive function performance in PD. Generally, dementia is still not remediable, early interventions might slow down the degenerative process[41–43]. Thus, our results suggest that SCD in patients with PD should engage in the intervention of rehabilitation training, it is of great value for the maintenance of overall cognitive function and avoid the continuous decline of language function. Future studies with greater sample sizes are recommended to explore more applications of rehabilitation training.
Several limitations of the present study need to be acknowledged: the limitations may be limited due to small sample size and comprehensive assessment of each cognitive subsets during the follow-up was not included which may not be reflective of other samples. Therefore, further studies with larger samples, a long-term follow-up period, and a more comprehensive neuropsychological assessment would be able to confirm these findings.
In summary, the clinical utility of language and related functions as an early marker for cognitive decline in Parkinson's disease deserves further exploration in longitudinal studies. PD patients with SCD should be carefully screened for the potential cognitive impairment. Early diagnosis and treatment of SCD are of great value in maintaining overall cognitive function and preventing continuous decline in language function.