The following table lists the presentations given at the 2006 Parkinson’s Disease Workshop, as well as the notes used to introduce each session. All lecture notes are courtesy of the person named and used with permission.
|1||Cognition in Parkinson’s Disease (PDF)||Almost 200 years after James Parkinson (1817) first reported the disease that bears his name, our understanding of the cognitive deficits caused by Parkinson’s disease (PD) is still incomplete. In some patients, cognitive problems are severe; approximately 10% to 15% PD patients meet the criteria for dementia (Mayeux et al., 1988; Growdon et al., 1990). Even in nondemented patients, however, specific cognitive deficits are striking. Approximately 60% of nondemented patients are impaired in at least one cognitive domain (Growdon et al., 1990), including cognitive control processes, memory, verbal ability, and visuospatial functions. Further, cognitive dysfunction may correlate with other clinical variables. For example, late-onset patients manifest cognitive deficits earlier than early-onset patients, even when additive contributions of disease duration and normal aging are taken into account (Locascio et al., 2003; Katzen et al., 1998). The administration of levodopa has also been shown to impair cognitive performance in PD (e.g., Cools et al., 2006), which may result from the selective over-dosing of neural regions that are relatively unaffected in PD.|
|2||Neuropathology and Structural Neuroimaging in Parkinson’s Disease (PDF 1) (PDF 2 - 1.4 MB)||The major neuropathologic feature of idiopathic Parkinson’s disease (PD) is a selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), accompanied by Lewy bodies and neurites, although neuropathological studies suggest abnormalities exist in other brain regions as well. Many of the cognitive deficits in PD may stem from abnormalities in nonmotor circuits of the basal ganglia (particularly the fronto-striatal loop, including the anterior caudate and dorsolateral prefrontal cortex), which may be affected by dopamine loss in the same way as the motor circuits. This workshop was designed to provide a broad overview of the most current literature regarding neuropathological and neuroimaging findings in idiopathic PD. The papers presented and discussed at this workshop focused on abnormalities in the striatum, brainstem, thalamus, hippocampus, amygdala, the cholinergic and serotoneric brainstem nuclei, and cerebral cortex. Current limitations and recent advances in the application of structural neuroimaging methods to studying PD were also discussed.|
|3||Genetics of Parkinson’s Disease (PDF - 2.1 MB)||
Parkinson’s disease (PD) has long been considered to be a sporadic condition, the causative factors of which consist mainly of environmental interactions. For example, much attention has been paid to the contribution of pesticide exposure (DiMonte, Lavasani, Manning-Bog, 2002; Betarbet, Sherer et. al, 2000), rural living (Priyadarshi, Khuder et al., 2001), and industrial metalworking (Jankovic, 2005). Although a family history is the second most important predictor of PD after age, such familial concurrence has often been construed to be the result of shared environmental factors rather than an indicator of heritability. Although twin studies investigating the concordance rates in PD have shown evidence for a heritable aspect in longitudinal studies (Piccini, Burn et al., 1999), no significant relation is seen in cross-sectional studies (Tanner, Ottman et al., 1999; Wirdefeldt, Gatz et al., 2004).
Over the past decade, several causative genes have been identified in kindreds demonstrating a Mendelian incidence of disease. Parametric, genome-wide association studies have also revealed multiple susceptibility loci (Pankratz, Nichols et al., 2002; Scott, Nance, et al., 2001). Besides a handful of exceptions, however, these genetic factors exhibit a greatly reduced penetrance and unique molecular pathologies that confound attempts to adequately explain the causes of sporadic PD. While it now appears that the disease has a significant genetic component, the causative factors of sporadic PD may represent a more heterogeneous balance of genetic predisposition and environmental exposure.
|4||Cognitive Control Processes and Working Memory in Parkinson’s Disease (PDF)||Early stage idiopathic Parkinson’s disease (PD) is characterized by the three classic motor symptoms: rigidity, tremor, and bradykinesia. The core pathological hallmark of PD is the progressive loss of dopamine (DA) neurons in the ventrolateral tier of the substantia nigra pars compacta which primarily projects to the dorsal striatum (Fearnley and Lees, 1991; Kish, Shannak, and Hornykiewicz, 1988). The severely DA depleted dorsal striatum sends efferents, via the nigrostriatal pathway, to the supplementary motor area and distinct areas of the PFC, namely the dorsolateral PFC and ventrolateral PFC (Middleton and Strick, 2000a; Middleton and Strick, 2000b). Less severely affected are direct dopaminergic projections from the ventral tegmental area (VTA) to the PFC via the mesocortical pathway (Uhl, Hedreen, and Price, 1985). Due to the strong reciprocal connections between the striatum and specific areas of the frontal cortex, PD pathology results in a host of executive deficits, such as planning, attentional set-shifting, and working memory. These cognitive deficits are similar, but not identical, to ones observed with frontal lobe damage (Owen et al., 1992). This set of slides describes the executive deficits after frontal lobe lesions, and then compares them to the executive deficits seen in PD.|
|5||A Systems Neuroscience Approach to Memory (PDF)||
How would you respond to the following questions:
What did you have for dinner last night?
What is the capital of Spain?
How do you maintain your balance when you ride a bicycle?
As you were thinking about the answer to each question, you were accessing information from different memory systems. Understanding that there are different kinds of memory, with different addresses in the brain, is the essence of the science of memory. The dissociation of memory processes includes a distinction between declarative or explicit memory (conscious retrieval of events and facts) and nondeclarative or implicit memory (expressed through performance without conscious referral to stored information). This workshop did not address the topic of nondeclarative memory in PD. Instead, the focus was on working memory (a kind of short-term memory that requires monitoring and manipulation of information) and long-term declarative memory for events (episodic memory). The brain network that supports episodic memory includes medial temporal lobe structures (hippocampus and surrounding cortices) in concert with areas within prefrontal cortex and posterior parietal cortex.
|6||Long-term Declarative Memory in Parkinson Disease (PDF) (Courtesy of Christie Chung.)||Although, Parkinson’s disease (PD) often leads to dementia, PD patients who do not develop dementia still show deficits in long-term memory (Kensinger, Shearer, Locascio, Growdon, and Corkin, 2003; Sagar, Sullivan, Gabrieli, Corkin, and Growdon, 1988). There is strong consensus that recall memory is impaired in nondemented PD patients (Brown and Marsden, 1990; Cooper, Sagar, Sullivan, 1993; Sahakian, 1988), but the status of recognition memory is controversial. Recognition memory is subserved by two processes according to dual-process models of memory: a) recollection - a vivid, clear memory of an item with the contextual details associated with it (subserved by prefrontal cortex, parietal cortex, and hippocampus proper), and b) familiarity - an intuitive feeling that the stimulus has been encountered recently without awareness of its context (dependent on the parahippocampal and perirhinal cortices, e.g., Yonelinas, 1998, 2005). Because PD impacts PFC and MTL structures, it is reasonable to predict a deficit in both recollection and familiarity in PD recognition performance. Further, with the evident recall deficit in PD, it is plausible to assume a greater recollection deficit than familiarity impairment in PD patients. Yet, Davidson et al. (2006) found that PD causes a deficit in familiarity but not recollection. Further, prospective memory (the ability to remember to execute an action at a future time point) and metamemory (ability to judge one’s own memory abilities) are also impaired in PD. When assessing memory capacities in PD patients, clinical depression (Mahieux et al., 1998; Norman et al., 2002) and disease severity (Lees and Smith, 1983; Owen et al., 1992; Whittington et al., 2000, 2006) should be considered carefully because both may impact memory performance.|