Cognition Deficits in Parkinson’s Disease: Mechanisms and Treatment

Abstract

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder mainly in middle-elderly population, which represents diverse nonmotor symptoms (NMS) besides such well-documented motor symptoms as bradykinesia, resting tremor, rigidity, and postural instability. With the advancement of aging trend worldwide, the global prevalence of PD is mounting up year after year. Nowadays, accumulating lines of studies have given a comprehensive and thorough coverage of motor symptoms in PD. Yet much less attention as compared has been paid to the nonmotor symptoms of PD, such as cognition deficits. Of note, a patient with PD who suffers from cognitive impairment may harbour a statistically significantly higher risk of progressing toward dementia, which negatively affects their life expectancy and daily functioning and overall lowers the global quality of life. Furthermore, it is a widely held view that cognitive dysfunction does not just occur in the late stage of PD. On the basis of numerous studies, mild cognitive impairment (MCI) is a harbinger of dementia in PD, which is observed as an intermediate state with considerable variability; some patients remain stable and some even revert to normal cognition. Considered that the timing, profile, and rate of cognitive impairment vary greatly among PD individuals, it is extremely urgent for researchers and clinicians alike to identify and predict future cognitive decline in this population. Simultaneously, early screening and canonical management of PD with cognitive deficits are very imperative to postpone the disease progression and improve the prognosis of patients. In our review, we focus on a description of cognitive decline in PD, expound emphatically the pathological mechanisms underlying cognition deficits in PD, then give a comprehensive overview of specific therapeutic strategies, and finally dissect what fresh insights may bring new exciting prospect for the subfield.

Biological Sex and Sex Hormone Impacts on Deficits in Episodic-Like Memory in a Rat Model of Early, Pre-motor Stages of Parkinson's Disease

“…Memory impairments, including those involving episodic memory, present in roughly 20% of PD patients at or before the onset of motor deficits (30) and afflict more than 50% of patients over the course of illness (20,26). Episodic memory impairments in particular can also predict a more rapid and more severe decline in motor and memory function (34,35) and signal a greater probability of developing PD-related dementia (26,36,37).…”

“…This may be especially important for the cognitive impairments associated with PD. These include deficits in executive, mnemonic and/or visuospatial function (4,(16)(17)(18)(19)(20) and are present in up to 40% of patients at or before the onset of motor signs (20,21). Because these signs are also largely resistant to (19,20,22) or exacerbated by (23)(24)(25) available therapeutics, the also have a cumulative prevalence of more than 70% over the course of illness (20,26).…”

“…These include deficits in executive, mnemonic and/or visuospatial function (4,(16)(17)(18)(19)(20) and are present in up to 40% of patients at or before the onset of motor signs (20,21). Because these signs are also largely resistant to (19,20,22) or exacerbated by (23)(24)(25) available therapeutics, the also have a cumulative prevalence of more than 70% over the course of illness (20,26). Moreover, these enduring, progressively worsening facets of disease (17)(18)(19)(20) are frequently described by patients and caregivers as significantly disabling and negatively interfering with activities and quality of daily life (27,28).…”

Predicting Cognitive Decline in Parkinson’s Disease with Mild Cognitive Impairment: A One-Year Observational Study

“…Several risk factors for the progression from mild cognitive impairment (MCI) to dementia have been identified, including age; female gender; lower educational attainment; an amnestic subtype of MCI; neuropsychiatric symptoms of anxiety, depression, or apathy; sleep disturbance; poor gait performance; obesity; metabolic syndrome; and common chronic medical conditions [ 1 – 5 ]. Parkinson's disease (PD) with MCI (PD-MCI) is an entity with a highly variable prognosis, including reversion to normal cognition, stability in the MCI state, or conversion to dementia [ 6 ]. Regardless of reversion to normal cognition or persistence, PD-MCI has a prognostic value for predicting dementia [ 7 ].…”

Overdosing on iron: Elevated iron and degenerative brain disorders

“…[143][144][145][146] In addition to the motor deficits, cognitive decline is also observed in a subset of patients and this is believed to be due to neuronal loss in other brain areas, of which the cortex and other basal ganglia areas are predominant. [146][147][148] Although the reason for selective vulnerability of SN dopaminergic neurons in PD remains unresolved, one widely accepted factor is the normally high level of oxidative stress in these neurons resulting from the degradation of dopamine by monoamine oxidase (MAO) generating H 2 O 2 , which in the presence of iron generates toxic hydroxyl radicals and other oxidative species which damage cellular macromolecules. 149,150 Dopamine can also be nonenzymatically oxidized in the presence of oxygen to yield harmful metabolites and free radicals.…”