Theory

Summary

Clinical Implications

The Braak Model

Braak, et al. (2003)

· PD progresses in a caudal-rostral fashion via 6 stages.

· Stages 1-2: Pathology initiates in peripheral regions. Patients are initially asymptomatic. Autonomic dysfunction present by stage 2.

· Stages 3-4: Pathology progresses to the subcortex. Symptoms include disturbed sleep, tremor, rigidity, and slowness of movement. MCI may arise due to disrupted neural connectivity.

· Stages 5-6: Pathology progresses to the cortex. Symptoms include cognitive impairment, possibly dementia.

· Non-motor symptoms (e.g., sleep, decreased olfaction) regulated by peripheral regions appear early in the disease, often before the traditional motor symptoms.

· Younger patients who have a longer clinical course tend to have pathology that fits with Braak’s model of progression, compared to those with older onset and shorter disease duration.

· Clinicians should continually assess non-motor symptoms as they often present in a dynamic manner.

The GO/NoGo Model

Frank (2006)

Frank, et al. (2004)

· The direct and indirect basal ganglia pathways interact to facilitate desired actions and inhibit undesired actions.

· Alterations in dopamine levels either enhance or impede functioning of the direct and indirect pathways.

· The effectiveness of positive versus negative feedback varies depending on dopaminergic medication status.

· Errorless learning approaches may be particularly useful with individuals with PD given impaired trial-and-error learning capabilities.

· Medication status may influence the effectiveness of reinforcement during therapy, with negative reinforcement more effective off medication and positive reinforcement more effective on medication.

· Some individuals with PD are particularly susceptible to pathological gambling and addiction with dopamine supplementation.

The Dopamine-Overdose Hypothesis

Cools, et al. (2001)

Swainson, et al. (2000)

· Dopaminergic medication will “refill” the dorsal striatum and enhance the associated cognitive functions (e.g., set-shifting), but can “overdose” the ventral striatum and degrade associated cognitive functions (e.g., reward performance, impulsivity).

· Improvement in the motor functions of PD can come at the expense of cognitive functions.

· Variability in treatment outcomes for cognitive goals may be driven by medication status.

· Motor sequence learning, important for instrumental activities of daily living such as technology use and driving, can become impaired by medication in early PD.

The Neural Networks Framework

Gratwicke, et al. (2015)

· Cognitive functions are influenced by overlapping neural networks. Degradation of these networks can lead to MCI or dementia.

· Executive dysfunction in PD results from dopamine depletion in the striatum and subsequent interruption of fronto-striatal networks.

· Impairments in attention, memory, and visuospatial perception may be attributed to degenerating cholinergic and noradrenergic pathways.

· Patients prescribed noradrenergic or cholinergic medications may have more advanced cognitive decline. The presence of these medications should cue clinicians to conduct thorough cognitive evaluations.

The Dual-Syndrome Hypothesis

Kehagia, et al. (2013)

· There are two primary cognitive phenotypes in PD.

· Dysexecutive syndrome: Primary deficits in working memory and executive functions, is mediated by fronto-striatal pathways, and is affected by dopaminergic medication.

· Dementia syndrome: Early-presenting deficits of visuospatial function and semantic fluency that are mediated by posterior-cortical regions, and not affected by dopaminergic medication. Impairments may be amenable to cholinergic medications.

· Early deficits in visuospatial skills and semantic fluency are associated with progression to dementia.

· Individuals may present with variable performance on cognitive tasks related to the dysexecutive syndrome once beginning medication.