The diagnosis of PD-MCI rests upon the concept that MCI, in general and specific to PD, refers to a clinical syndrome of cognitive impairment in the absence of dementia. However, as the studies of PD-MCI illustrated in this review demonstrate, the diagnosis of PD-MCI has been made in many different ways and using various definitions; these factors likely influence our current knowledge of frequency estimates and characteristics of PD-MCI. Operational definitions of PD-MCI are currently underway by the MDS Task Force on PD-MCI. This section will explore issues pertaining to diagnostic criteria, effects of associated co-morbidities in PD, challenges in the cognitive assessment of PD patients, and screening tests ().
Issues to consider in the diagnosis of PD-MCI
In keeping with established MCI criteria, many of the studies of MCI in PD have utilized established criteria 19, 22
or modified versions of these. Items often modified pertain to the presence of memory complaints, preservation of activities of daily living, and documentation of memory (or other cognitive) impairment according to different reference values. Few PD-MCI studies have required the presence of a memory (or cognitive) complaint by the patient. Since nonamnestic deficits such as executive dysfunction are more common than memory ones, subjective complaints of memory in PD may not be the most appropriate requirement for the diagnosis of PD-MCI; this item may need to be expanded to broadly address complaints in all cognitive areas. Furthermore, estimates of cognitive impairment by patients and their caregivers may not be reliable due to either over or under-reporting 30, 54, 55
or to difficulty separating cognitive from motor problems. Thus, information from several sources (e.g., patient, caregiver, and clinician) may be needed to determine if a patient has declined cognitively. In addition, PD-MCI studies vary in the manner in which the preservation of activities of daily living is evaluated. This issue is particularly challenging in PD since daily activities may be profoundly affected by PD motor symptoms; specific measures that distinguish the cognitive from motor effects on daily functioning and sensitive cognitive measures to identify functional impairment are needed. 56
Although the established MCI criteria do not specify how many neuropsychological tests or which tests should be used, what cognitive domains and how many should be examined, what normative data should be used, or which cut-off scores should be employed, these are important considerations in the diagnosis of PD-MCI and the development of operational definitions. The PD-MCI studies previously described have handled these issues pertaining to neuropsychological tests (e.g., number of neuropsychological tests, specific tests, number of cognitive domains, sources of normative data, and cut-off scores) in various ways. Studies illustrate that the use different cut-off scores (ranging from 0.5 to 2 SD below normative data) greatly influence frequency estimates of PD-MCI. When only a single neuropsychological test, rather than 1 of 5 cognitive domains, was required to be ≤ -1.5 SD, the reported number of PD-MCI cases doubled. 30
Different cut-off scores change the classification of not only PD-MCI cases but also controls 57
; when 2 scores in 1 cognitive domain fell 2 SD below normative values, rates of MCI were 14% in PD and 0% in controls, but when only 1 score in 1 domain was 1 SD below normative values, MCI occurred in 89% of PD and 70% of controls.
Motor and non-motor features of PD may affect cognitive function in PD and thereby, the diagnosis of PD-MCI. Cognitive performance may differ in “on” versus “off” motor states, particularly in tests of executive function and also in those PD patients with motor fluctuations. 58, 59
Neuropsychological tests with timed components or significant motor demands may be difficult for PD patients to complete. Non-motor features such as depression, anxiety, apathy, psychosis, fatigue, and sleep disturbances are common in PD, particularly in those patients with impaired cognition or dementia. 9, 11
These associated non-motor features may interfere with cognitive testing and interpretation of neuropsychological test results. Thus, motor and non-motor co-morbidities in PD pose unique challenges in the evaluation of PD patients and classification of cognitive status.
There are many neuropsychological tests available to evaluate cognitive functions (e.g., executive function, attention, psychomotor speed, language, visuospatial abilities, and memory). As such, it is likely beyond the scope of any MCI (or dementia) criteria to prescribe specific neuropsychological tests. It is useful, however, for a comprehensive evaluation to include tests that capture each cognitive domain, have been well-studied and validated, and have appropriate normative data; diagnostic procedures for PD-MCI and PDD provide examples of tests frequently used in evaluating cognitive impairment in PD. 60, 61
Several global cognitive scales have been proposed as screening tests for PD-MCI and/or PDD, including the MoCA, SCOPA-COG, Parkinson Neuropsychometric Dementia Assessment (PANDA), PD-Cognitive Rating Scale (PD-CRS), and Mattis DRS among others; most of these tests take about 10-30 minutes to administer. 62, 63
The MoCA, which was originally developed to screen for MCI in the general population, assesses orientation, executive function, attention/concentration, naming, verbal abstraction, and visuoconstructive abilities. Although the MoCA performed better in detecting PDD, it had an acceptable sensitivity (0.83), but low specificity (0.53) using a cutoff of 26/27 in detecting MCI in one PD study. 64
In another study of PD patients, of whom 21/114 (18%) had PD-MCI, the MoCA, SCOPA-COG, and standardized MMSE demonstrated excellent discrimination of PDD from non-demented PD and PD-MCI from cognitively normal PD; the MoCA in particular performed well, with an optimal screening cut-off for PD-MCI of <26/30 having 90% sensitivity, 75% specificity, and a negative predictive value of 95%. 65
The SCOPA-COG, which includes tests of nonverbal and verbal memory, attention, executive function, verbal fluency, and visuospatial function, is reliable and sensitive to PD cognitive deficits. A large study of 400 PD patients and 150 healthy controls replicated validation studies and also detected cognitive impairment in 88 PD patients as well as in 50/88 (58%) of those PD with normal MMSE scores. 36
The PANDA which includes tests of immediate and delayed recall memory, alternating verbal fluency, visuospatial abilities, and working memory/attention has been reported to discriminate between PDD, PD-MCI, non-demented PD, and controls; however, in its current form, the scale lacks assessment of language function; data on clinimetric scale properties, construct validity, and test-retest reliability, assessment; and clearly defined PD-MCI population, which may necessitate additional study. 66
The PD-CRS scale assesses not only frontal-subcortical but also posterior cortical deficits in PD with tasks of sustained attention, working memory, alternating and action verbal fluency, clock drawing, immediate and delayed free-recall verbal memory, confrontation naming, and clock copying. 12
The PD-CRS differentiated between PD-MCI and PDD patients and also between PD-MCI and cognitively intact PD patients; items of alternating verbal fluency and delayed verbal memory independently differentiated the PD-MCI group from both controls and cognitively intact PD. The Mattis DRS, a measure of global cognitive function but with an emphasis on frontal-lobe dysfunction, has been widely used in PDD with cut-off scores of < 123 frequently specified. Compared to the other screening tests, the DRS takes longer to administer, requiring about 20-30 minutes. 67
In a recent study of 40 PD patients, the DRS demonstrated a sensitivity of 72% and specificity of 86% to correctly classify 80% of PD-MCI, using a normality cut-off of 138. 68