Elsevier

Ageing Research Reviews

Volume 74, February 2022, 101508
Ageing Research Reviews

Review
Subjective cognitive decline in idiopathic Parkinson´s disease: A systematic review

https://doi.org/10.1016/j.arr.2021.101508Get rights and content

Highlights

  • High prevalence of mild cognitive impairment in the course of Parkinson’s disease.

  • Subjective cognitive decline marks a growing interest as a preclinical stage.

  • SCD is a decline in subjective cognitive capacities, while cognitive test results are normal.

  • SCD is a new concept in persons with Parkinson’s disease.

  • SCD may allow for earlier detection and may be considered for prevention.

Abstract

Cognitive symptoms of Parkinson’s disease (PD) have been long underestimated, but are some of the most disabling non-motor features of the disease. In order to establish signs that allow for earlier detection of cognitive decline in PD, the concept of `subjective cognitive decline´ (SCD) has gained a growing interest. SCD refers to patients who report a decline in subjective cognitive capacities, while their results on neuropsychological tests are within the normal performance range, indicating adequate cognitive functions. The aim of this review was to evaluate the concept of SCD in PD and give an overview of the current research. A systematic literature search in PubMed was performed to identify articles published before December 2020. We included 18 studies with a total of n = 2,654 patients. While there is currently no consensus on research or clinical criteria for SCD in PD, this review presents the accumulated evidence for SCD in PD patients and supports the importance of early identification of cognitive deficits, due to the relatively high prevalence for SCD in PD and the added risk of future cognitive impairment it entails. The publications included in this review indicate that SCD may be part of the PD spectrum but further research is needed. Expanding research on SCD in PD will allow for earlier detection of cognitive impairment and may foster preventive interventions.

Introduction

Cognitive dysfunction is one of the most prominent and disabling features in patients with Parkinson’s disease (PD) (Kehagia et al., 2010). Up to 80% of PD patients will develop dementia during the course of the disease (Obeso et al., 2017). The course of cognitive decline in PD patients has become a major topic of interest in recent years. In 2007, clinical diagnostic criteria for dementia in PD (PD-D) were established (Dubois et al., 2007, Emre et al., 2007) and in 2012, the concept of Mild Cognitive Impairment in PD (PD-MCI) was introduced (Litvan et al., 2012). Prior to the development of the MDS PD-D criteria, Aarsland et al. (2005) found dementia in 24–31% of individuals diagnosed with Parkinson syndrome, estimating 3–4% of dementia cases in the general population to be due to PD-D. More current results show a similar prevalence rate of 29% (range: 12.2–59.4%) with dementia, depending on age and severity of clinical symptoms (Riedel et al., 2010).

Over time, the majority of PD-patients will develop dementia, as the risk for PD-D increases with age and duration of the disease (Emre et al., 2007, Riedel et al., 2010). The longitudinal Sydney study found in a 15 year follow-up of newly diagnosed PD-patients that 48% of patients showed evidence of dementia, 36% presented mild cognitive impairment, and 15% had no cognitive impairment (Hely et al., 2005). After a time period of 20 years at total of 83% of the surviving PD-patients of the cohort had developed dementia (Hely et al., 2008).

Similar to Mild Cognitive Impairment(Petersen, 2004), the concept of SCD has first been conceptualized in the field of Alzheimer research (Reisberg et al., 1982, Reisberg et al., 2008). The Subjective Cognitive Decline Initiative (SCD-I), an international consortium aiming to define SCD in Alzheimer’s disease, recently provided a conceptual framework and defined the two basic features of SCD: 1) “Self-experienced persistent decline in cognitive capacity in comparison with previously normal status and unrelated to an acute event” and 2) “Normal age-, gender-, and education-adjusted performance on standardized cognitive tests, which are used to classify mild cognitive impairment (MCI) or prodromal AD” (Jessen et al., 2014, Table 1). In addition, the SCD-I group provided a series of SCD plus features that indicate a higher risk of future objective cognitive decline in individuals who meet the two basic SCD criteria (Jessen et al., 2020). Importantly, research criteria for the differentiation of MCI and SCD have been described.

Fulfilling these criteria may have various underlying causes and not all of them are linked to a neurodegenerative disorder. The vast majority of people with SCD do not progress to any form of dementia (Slot et al., 2019). However, in the 2018 NI-AA research framework on Alzheimer’s disease SCD is described as an at-risk state for dementia: “A subset of cognitively unimpaired individuals who may report subjective cognitive decline and/or demonstrate subtle decline on serial cognitive testing” (Jack et al., 2018, Table 3, p. 546).

In their systematic review, including 17 papers, Mendonça and colleagues reported risk factors regarding the conversion from SCD to MCI and dementia including problems with activities of daily living and affirmation by an informant. Importantly, SCD was also related to a higher risk of conversion to dementia (Mendonça et al., 2016). Thus, in the course of AD, SCD is seen as a risk factor for MCI, which in turn, is thought a prodromal stage of dementia (Arnáiz and Almkvist, 2003, Jessen et al., 2010). Therefore, the stage of SCD entails an increased risk for cognitive decline and conversion to dementia and is seen as an important part of the AD trajectory (Buckley et al., 2016, Jessen et al., 2020). Underlying brain activation indicates compensatory mechanisms in individuals with SCD as the typical β-amyloid deposition and atrophy could be found even at the SCD stage(Sun et al., 2015). Thus, assessment of SCD enables earlier prediction on disease severity over time and the SCD phase might be used successfully for interventions and therapy initiation.

In an article comparing the rates of progression from SCD to AD and other forms of dementia, Slot and colleagues found the incidence rate per 1000 person-years of 11.5 for patients with SCD to progress to AD and 6.1 to non-AD in comparison to 10.1 for AD and 4.1 for non-AD in patients without SCD. This article further highlights that despite the little focus on the SCD stage of non-AD patients so far, approximately one in three cases of dementia following the SCD stage is not due to AD. (Slot et al., 2019).

Based on this research in patients with Alzheimer´s disease (AD), a corresponding three-stage clinical manifestation has been hypothesized for PD: with subjective cognitive decline (SCD) as an at-risk state, followed by mild-cognitive impairment (MCI), finally leading to dementia (Erro et al., 2014, Hogue et al., 2018).

Overall, cognitive impairment in PD is increasingly recognised as a significant feature of the disease, which is accompanied by increased caregiver burden. A recent study found cognitive decline in PD associated with increased costs, even in non-demented subjects. The costs of patients with PD-D were 3.3 times higher than those of non-demented PD patients, with institutional care as the largest cost factor (Vossius et al., 2011). The aim of this review is to evaluate whether the concept of SCD is applicable to PD and to describe the current state of the research. Identifying patients with SCD at an at-risk state early in the course of PD could enable clinicians to delineate progression to PD-D more accurately. This in turn might allow early intervention and delay the onset of dementia.

Section snippets

Search strategy

We conducted a systematic search in the database “PubMed” for references published prior to December 2020. We used the following search terms: “Parkinson’s disease” (PD) combined with (AND) either “subjective cognitive decline” (SCD), “subjective memory decline” (SMD), “subjective memory impairment” (SMI), “subjective memory complaint(s)” (SMC), “subjective cognitive impairment” (SCI) or “subjective cognitive complaint(s)” (SCC). A MESH term for SCD is currently not available in PubMed. The

Results and discussion

This review aims to give an overview of the existing research on SCD in PD: currently, no specific criteria are available for SCD in patients with PD (PD-SCD) (Aarsland et al., 2017). Despite SCD being a generic description for early experienced cognitive deficits, most research so far has focused on SCD in the context of AD. But in contrast to AD, memory impairment is not the leading cognitive complaint in PD, however, the current SCD criteria defined by Jessen et al. focus on memory (Jessen

Conclusion

In recent years, the study of preclinical stages of cognitive impairment has gained more and more attention. From the current state of the literature, it seems that the subtle cognitive decline of SCD is indeed an at-risk stage for of MCI and dementia in PD.However, while SCD in PD has been gaining some attention in the recent past, there are still a number of unresolved questions.

So far, studies on PD-SCD are lacking an unanimous SCD definition. Moreover, there is a wide range of very

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