Parkinsons Dis. 2014;2014:507529. doi: 10.1155/2014/507529.

Influence of hypertension on neurocognitive domains in nondemented Parkinson’s disease patients.

Jones JD1, Jacobson C2, Murphy M3, Price C1, Okun MS4, Bowers D5.
  • 1Department of Clinical and Health Psychology, McKnight Brain Institute, University of Florida, 101 South Newell Drive, Gainesville, FL 32601, USA ; Center for Movement Disorders and Neurorestoration, McKnight Brain Institute, University of Florida, 3450 Hull Road Gainesville, FL 32607, USA.
  • 2Center for Movement Disorders and Neurorestoration, McKnight Brain Institute, University of Florida, 3450 Hull Road Gainesville, FL 32607, USA.
  • 3Department of Internal Medicine, McKnight Brain Institute, University of Florida, P.O. Box 100277, Gainesville, FL 32610-0277, USA.
  • 4Center for Movement Disorders and Neurorestoration, McKnight Brain Institute, University of Florida, 3450 Hull Road Gainesville, FL 32607, USA ; Department of Neurology, McKnight Brain Institute, University of Florida, HSC, P.O. Box 100236, Gainesville, FL 32610, USA.
  • 5Department of Clinical and Health Psychology, McKnight Brain Institute, University of Florida, 101 South Newell Drive, Gainesville, FL 32601, USA ; Center for Movement Disorders and Neurorestoration, McKnight Brain Institute, University of Florida, 3450 Hull Road Gainesville, FL 32607, USA ; Department of Neurology, McKnight Brain Institute, University of Florida, HSC, P.O. Box 100236, Gainesville, FL 32610, USA.

 

Abstract

Objective. Health comorbidities, particularly cardiovascular risk factors, are well known to pose risks for cognitive decline in older adults. To date, little attention has focused on the impact of these comorbidities on Parkinson’s disease (PD). This study examined the prevalence and contribution of comorbidities on cognitive status in PD patients, above and beyond the effects of disease severity. Methods. A cross sectional design was used, including neuropsychological data on 341 PD patients without severe cognitive decline. Comorbidity data were collected via medical chart review. Data were analyzed using a series of multiple hierarchical regressions, controlling for PD-related disease variables. Results. Overall sample characteristics are 69% male, disease duration 9.7 years, Unified Parkinson’s Disease Rating Scale 26.4, and age 64.7 years. Hypercholesterolemia (41.6%), hypertension (38.1%), and hypotension (30.2%) were the most reported comorbidities. The presence of hypertension significantly contributed to domains of executive function and verbal memory. The cooccurrence of orthostatic hypotension moderated the relationship between hypertension and executive function. Conclusions. This study on a large cohort of PD patients provides evidence for a detrimental influence of health comorbidities, particularly hypertension, on cognitive domains that have traditionally been conceptualized as being frontally and/or temporally mediated.

PMID: 24587937

 

Supplements:

Cognitive impairment is a common symptom in Parkinson’s disease. About 5-20% of individuals with Parkinson’s disease show signs of cognitive impairment when initially diagnosed, with up to 80% of these patients developing dementia within 20 years (Aarsland, 2004; Hely et al., 2008). One mechanism contributing to cognitive impairment in Parkinson’s is disruption of frontal-subcortical circuits secondary to dopamine striatal dopamine depletion. Additional studies support the role of cholinergic depletion secondary to basal forebrain dysfunction, and Alzheimer’s pathology contributing to cognitive deficits in Parkinson’s disease (Jellinger, 2012; Hilker et al., 2005). Limited studies have focused on the detrimental role of cardiovascular risk factors on cognition in Parkinson’s disease, despite the fact that over two decades of studies have shown cardiovascular risk factors to be related to slowed processing speed and frontal-executive dysfunction.

One may ask the question “why examine the influence of cardiovascular risk factors on cognition in Parkinson’s disease if the relationship has been shown to exist in normal elderly samples?” The answer relates Parkinson’s disease being associated with both protective and risk factors of cardiovascular disease (Nanhoe-Mahabier et al., 2009). Specifically, both levodopa medication and degeneration of the locus coeruleus secondary to Lewy body depositions may lead to decreased norepinephrine levels, which lead to blood vessel dilation, decreased cardiac output and ultimately lower blood pressure. On the other hand, Parkinson’s disease is associated with decreased mobility and increased homocysteine levels (secondary to levodopa) that may increase an individual’s vulnerability to cardiovascular disease.

Findings from the current study showed a relationship between hypertension and lower scores of tests of executive functioning and verbal delayed recall. This result was corroborated by the finding that higher pulse pressure values (a surrogate measure of cardiovascular risk) related to worse cognitive functioning in domains of executive function, verbal delayed recall and processing speed. Furthermore, individuals with more severe Parkinson’s disease motor symptoms (measured by a clinician rated scoring system; Unified Parkinson’s Disease Rating Scale motor scores) showed a stronger relationship between pulse pressure and cognitive impairment (Figure 1).

 

fig1Figure 1. Pulse Pressure X UPDRS Interaction for 3 cognitive domains. Figure depicts linear relationship between pulse pressure and executive function, delayed verbal memory and processing speed for each Unified Parkinson Disease Rating Scale Part III (UPDRS) quartile (higher quartile means more severe motor symptoms). The relationship between pulse pressure and cognition was strongest among individuals in the lowest UPDRS quartile (most severe motor symptoms).

 

Findings were contrary to previous studies examining the influence of cardiovascular risk factors on dementia status in Parkinson’s disease, but consistent with a wealth of literature among normal elderly individuals showing cardiovascular risk factors to negatively impact specific neurocognitive domains. The relationship between cardiovascular risk factors and cognitive impairment is likely due to small vessel disease associate chronic cerebral hypoperfusion (Libon, 2005). Deep subcortical white matter is particularly vulnerable to chronic mild drops in blood perfusion, due to receiving a less direct supply of blood. Damage to deep subcortical white matter may disrupt frontal-subcortical circuits important for cognitive functioning. Specifically white matter tracts connecting the dorsal-lateral prefrontal cortex (a cortical area important for executive functioning), the striatum, and the thalamus may be damaged among individuals with chronic hypertension. The finding of an interaction between pulse pressure and Parkinson’s disease motor severity is particularly interesting and may suggest that the frontal-subcortical circuits may be receiving a double hit (dopamine deficiency and white matter disruption) among individuals with both Parkinson’s disease and hypertension (Figure 2).

Overall, this study supports the view that cardiovascular risk factors are related to cognitive impairment in Parkinson’s disease, similar to what has been reported in normal aging. Even though levodopa use may be associated with the fringe benefit of lowering blood pressure, hypertension is still common among individuals with Parkinson’s disease, and has a detrimental impact on cognition.

 fig2

Figure 2. Parkinson’s and Vascular Pathology Effecting Frontal-Subcortical Circiuts. Figure portrays frontal-subcortical circuits important for cognition (Alexander, Delong & Strick, 1986). Disruption of these circuits may be due to: 1) substantia nigra degeneration in Parkinson’s disease (PD) leading to dopamine (DA) deficiency and 2) disruption of white matter tracts (internal capsule and thalamic projections) between grey matter structures.

 

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