eMedicine Specialties > Psychiatry > Geriatric

Parkinson Disease Dementia

Author: Margaret M Swanberg, DO, Assistant Professor of Neurology, Uniformed Services University; Chief of Neurobehavior Service, Walter Reed Army Medical Center; Assistant Chief, Department of Neurology, Walter Reed Army Medical Center
Coauthor(s): Raj K Kalapatapu, MD, Fellow in Geriatric Psychiatry, Mount Sinai School of Medicine
Contributor Information and Disclosures

Updated: Apr 15, 2009

Introduction

Background

Parkinson disease (Parkinson's disease, PD) is a disabling, progressive condition that is predominantly thought of as a movement disorder. In 1817, when James Parkinson originally described the "shaking palsy," he stated that cognitive changes are not evident until the later stages of the disease but that the disorder is often complicated by a spectrum of cognitive deficits that range from isolated cognitive impairment to severe dementia.

The overall incidence of cognitive impairment in Parkinson disease increases with age from 2.7% per year at age 55-64 years to 13.7% per year in the 70-79 year age group.¹ The prevalence of dementia in Parkinson disease ranges from 20-40%, with the disease conferring a 2- to 6-fold increased risk compared with control populations.² In the affected age group, comorbidity with other neurodegenerative disorders, particularly Alzheimer disease (Alzheimer's disease, AD) and cerebrovascular disease, is common. The relatively high prevalence of depression in patients with Parkinson disease is another confounder in the diagnosis of Parkinson disease dementia (PDD).

The clinical manifestations of Parkinson disease dementia are generally distinguishable from what are termed cortical dementias; however, these disorders largely overlap other disorders that manifest the typical subcortical pattern.

Case study

A 75-year-old man lives at home with his daughter. His diagnoses include probable dementia secondary to Parkinson disease, generalized anxiety disorder, and hypertension. His mini-mental state examination (MMSE) score at age 72 was 25/30, and his current MMSE score is 22/30. His current medications are carbidopa 25 mg/levodopa 100 mg, 2 tab tid; citalopram 40 mg daily; and lisinopril 20 mg daily. His gait is shuffling, and he has a significant resting tremor, which still causes difficulty with writing. He constantly worries about what might happen in the environment, from worrying that the subway will break down on his way to his appointment, to the elevator being stuck on his way up to his psychiatrist's office.

Pathophysiology

Cognitive deficits are due to the interruption of frontal-subcortical loops that facilitate cognition and that parallel the motor loop. Fibers from various areas of the cortex (eg, posterior parietal, premotor) converge on the striatum (particularly the head of the caudate) and project to the prefrontal cortex via direct and indirect loops affecting nigral, pallidal, and thalamic structures. Different areas of the caudate project to different areas of the prefrontal cortex. Damage to the pathways connecting the structures or damage to the structures themselves can elicit the frontal-like cognitive deficits that characterize cognitive dysfunction in Parkinson disease.

Dementia is likely due to a dopamine deficiency caused by nigral degeneration compounded by the loss of inputs from noradrenergic and cholinergic nuclei (locus coeruleus and nucleus basalis of Meynert, respectively).

Pathologic substrates in Parkinson disease dementia include neuronal loss, basal forebrain degeneration, neurofibrillary tangles, neuritic plaques, and Lewy bodies. The neuronal loss is most notable in the substantia nigra and the striatum. At the molecular level, alpha-synuclein is the principal pathologic protein, being found in the Lewy bodies and Lewy neurites of both Parkinson disease, Parkinson disease dementia, and dementia with Lewy bodies (another dementia with a large degree of clinical and pathologic overlap with Parkinson disease dementia).^3,4

Depression is likely due to a combination of factors.⁵ Some evidence suggests the psychological-reactivity model, where depression is positively correlated with severity, duration, and disability in Parkinson disease dementia; however, the evidence is inconsistent. Other evidence suggests that depression may be due to dopaminergic, noradrenergic, and/or serotonergic deficits.

Frequency

United States

Frequency of dementia in Parkinson disease is variable with most estimates, ranging from 20-40%, and has wide ranging affects on quality of life and survival.

A community-based population study found the prevalence of Parkinson disease to be 99.4 cases per 100,000 persons (2.3/100,000 in patients aged <50 y and 1,145/100,000 in patients >80 y). Approximately 41.3% of these patients had dementia. The frequency of dementia increases with age (approximately 3% of patients aged 50-59 y and almost 14% of patients aged 70-79 years had dementia).

In terms of coincident dementia, a prospective cohort study in New York City revealed that 19.2% of patients with Parkinson disease developed dementia after 2 years of follow-up care.

Risk factors for development of dementia include age, lower education, male gender, presence of hallucinations, depression, sleep disturbance, and disease duration.⁶

International

In a prospective longitudinal study in Leeds, United Kingdom, survival analysis showed that the cumulative incidence of dementia in a Parkinson disease cohort after 37 months was 19%. This translates into 47.6 cases per 1000 person-years of observation.

A cohort study in Scotland observed 249 patients with Parkinson disease for 3.5 years and found that 23.6% developed dementia.

In Norway, prevalence of dementia in patients with Parkinson disease is 27.7%.

Mortality/Morbidity

Mortality and morbidity may be higher in patients with Parkinson disease and dementia than in those with Parkinson disease without dementia.

Race

Parkinson disease occurs throughout the world, and no clear evidence indicates that the risk of developing dementia differs among racial or ethnic groups.

Sex

Older men develop Parkinson disease, with or without dementia, approximately twice as often as women do.

Age

The age of onset of Parkinson disease is one of the strongest risk factors for the development of dementia.

• Dementia is very rare, even with disease of long duration, when the age of onset is younger than 50 years.
• Patients whose Parkinson disease first arises at an advanced age are more likely to experience dementia, particularly if they are older than 70 years.

Clinical

History

• The development of dementia in patients with Parkinson disease is associated with the following factors:
  • Male gender
  • Parkinson Disease Rating Scale (PDRS) score more than 25
    • The PDRS is a rating tool used to follow the longitudinal course of Parkinson disease. It consists of 3 subsections: (1) mentation, behavior, and mood; (2) daily living activities; and (3) motor function.
    • A score of 25 signifies moderate impairment.
  • Depression
  • Development of mania, agitation, disorientation, or psychosis when treated with levodopa
  • Fluctuations in cognition
  • Exposure to psychological stress
  • Presence of cardiovascular abnormalities
  • Low socioeconomic status
  • Low educational level
• Cognitive impairment and poor prognosis are more common when patients have bradykinesia and postural and gait disturbance. Tremor or other parkinsonian signs are not associated with dementia.
• The presence of dementia within 12 months of the onset of motor features is generally not supportive of a diagnosis of Parkinson disease. It suggests dementia with parkinsonian features, most notably dementia with Lewy bodies (see Differentials). However, the line separating these 2 conditions is becoming less and less clear from a clinical, molecular, and pathologic viewpoint.

Physical

Case study

On mental status examination, the 75-year-old man described above (see Background) appears in street clothes and has good hygiene. He is cooperative and pleasant. His gait is shuffling, and he has significant resting tremor. He says his mood is fine, although he describes many worries. His affect is blunted. His speech is hypophonic with mild dysarthria. His thought processes are logical, sequential, and goal-directed. He denies auditory or visual hallucinations. No delusions are elicited. No suicidal/homicidal ideations or plans are elicited. His cognition is limited, based on MMSE. His insight into his illness is fair, stating he can't move around as he used to when he was younger. His judgment is fair, stating that he would like his daughter to be involved in his medical care.

Clinical features

A distinctive clinical phenotype for Parkinson disease dementia has not been established. Patients with Parkinson disease exhibit a spectrum of cognitive abnormalities, ranging from impairment in specific cognitive domains to severe dementia. Difficulties in describing the clinical phenotype of Parkinson disease dementia are in part due to early studies using tests that were confounded by the motor slowing associated with Parkinson disease.

• Mild cognitive changes on detailed neuropsychological tests are almost ubiquitous. The most common difficulty in patients with Parkinson disease is in the domain of executive function or a mild subcortical dementia characterized by deficits in word list generation, shifting sets, problem solving skills, and a retrieval type memory deficit.  
• Disorders of executive function
  • This is the core early deficit in disorders of the basal ganglia. Interruption of the striatal-pallidothalamic-dorsolateral circuit is likely the anatomic basis of executive dysfunction in Parkinson disease and other movement disorders. Difficulties in generating, maintaining, shifting, and blending of sets characterize executive function disorders, which manifest as mental inflexibility.
  • Nondemented patients with Parkinson disease display decreased generation and maintenance of sets and slowness in shifting sets in new situations. They show no impairment when performing overlearned tasks, and they benefit from external cues and structure. Difficulty occurs when shifting attention to novel stimuli.
• Visuospatial difficulties
  • Visuospatial deficits are reported in Parkinson disease; however, many studies suggest that these deficits are not an integral part of the disorder. Neuropsychological testing reveals deficits resulting in difficulty with line orientation, block design, and picture arrangement. These deficits are known to increase with advancing age in patients with Parkinson disease.
  • The most severely impaired patients show deficits in non–familiar-face discrimination. Deficits are present even when motor impairment is absent.
• Memory deficits
  • Frontal-subcortical systems are essential for organized recall of information. Damage to these systems leads to retrieval deficits in declarative memory and to abnormalities in procedural memory.
  • Patients with Parkinson disease and dementia experience immediate and long-term memory impairment. Providing patients with cues can improve memory performance.
  • Patients with Parkinson disease and dementia tend to do better on recognition tasks than patients with Alzheimer disease.
  • Patients with Parkinson disease are disproportionately impaired in their ability to temporally order or sequence new information.
• Language abnormalities
  • Aphasia is uncommon in Parkinson disease; however, speech disorders affecting articulation are prevalent. This can manifest as reiterative disorders and dysarthria.
  • "Tip of the tongue" phenomenon is common and consists of decreased naming and fluency.
  • Patients with Parkinson disease may have difficulty comprehending syntactically embedded questions. Their sentences tend to be grammatically simple.
  • Patients with Parkinson disease and dementia exhibit greater deficits in length of phrases, melody of speech, information content of spontaneous speech, and comprehension of verbal and written commands compared with patients who have Parkinson disease without dementia.
• Dementia
  • Based on clinical and neuropathologic criteria, Cummings has suggested that dementia in Parkinson disease can take the following 3 forms:
    • Dementia can be mild and show the clinical features of classic subcortical dementia.
    • Dementia can be more severe, with cortical features, but still be neuropathologically different from Alzheimer disease.
    • Dementia can be the more severe form, characterized pathologically by changes in the basal ganglia and the cortex. The cortex changes resemble those observed in Alzheimer disease (ie, neurofibrillary tangles, senile plaques).
  • Clearly defined criteria do not exist. According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)⁷ , dementia involves memory impairment (especially impairment in memory retrieval); a decline in functional level; and one or more cognitive disturbances, including aphasia, apraxia, agnosia, and disturbance in executive function. Disturbance in executive function is the most common; apraxia and agnosia rarely occur. Language disturbances occur in Parkinson disease but do not constitute full-blown aphasia. The criteria require evidence that the dementia is due to Parkinson disease and that the deficits do not occur exclusively during the course of delirium.
  • The features of dementia are frontal-subcortical and are most commonly mild to moderate in severity. Those patients with more severe dementia are more likely to have concomitant Alzheimer or Lewy body dementia pathology.
  • Patients with dementia present with bradyphrenia (slowness of thought processes), memory retrieval deficits, impaired set shifting and maintenance, impaired problem solving, poor visuospatial function, decreased fluency, and other language abnormalities. They often have prominent mood disorders.
  • Patients with Parkinson disease who have both dementia and depression have more severe disabilities and experience faster cognitive decline.
  • Dementia is more common in patients with akinetic-rigid syndromes than in those with predominating tremors.
  • Atypical neurologic features of Parkinson disease (eg, early occurrence of autonomic failure, symmetrical disease presentation, moderate response to dopamine agonists) are associated with more severe dementia.
• Psychiatric
  • Psychiatric symptoms^8,9 in patients with Parkinson disease can include depression, anxiety, sleep disturbance, psychosis, irritability, agitation, cognitive dysfunction, delirium, and apathy. In patients treated with dopamine agonists, clinicians should monitor for psychosis, mania, pathological gambling, hypersexuality, compulsive shopping, and binge eating.
  • Patients with Parkinson disease, even without dementia, respond slowly to questions and requests. They are usually dependent, fearful, indecisive, and passive. As the disease progresses, they become increasingly dependent upon spouses or caregivers.
  • Findings on mental status examination may include:
    • Appearance - Stooped posture, shuffling gait
    • Attitude - Irritability, agitation
    • Behavior - Delirium, apathy
    • Psychomotor - Resting tremor, bradykinesia
    • Affect -Masklike facies
    • Mood - Depression, anxiety
    • Speech - Slowing, generally hypophonic, some dysarthria and/or stuttering
    • Thought processes - Slowing
    • Thought content - Suicidal and/or homicidal ideations, psychosis
    • Cognition - Cognitive impairment, dementia
    • Insight - May be limited if dementia is present
    • Judgment - Nay be limited if dementia is present

Causes

• Most cases of Parkinson disease are sporadic (ie, do not occur in geographic, racial, ethnic, or genetic clusters).
• A minority of patients have familial inheritance.

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