Parkinson Disease Dementia - Parkinson's Dementia

Parkinson Disease Dementia

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:
(1) Dementia can be mild and show the clinical features of classic subcortical dementia.
(2) Dementia can be more severe, with cortical features, but still be neuropathologically different from Alzheimer disease.
(3) 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:
(1) Appearance - Stooped posture, shuffling gait
(2) Attitude - Irritability, agitation
(3) Behavior - Delirium, apathy
(4) Psychomotor - Resting tremor, bradykinesia
(5) Affect -Masklike facies
(6) Mood - Depression, anxiety
(7) Speech - Slowing, generally hypophonic, some dysarthria and/or stuttering
(8) Thought processes - Slowing
(9) Thought content - Suicidal and/or homicidal ideations, psychosis
(10) Cognition - Cognitive impairment, dementia
(11) Insight - May be limited if dementia is present
(12) 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.


DIFFERENTIAL DIAGNOSES

Alzheimer Disease
Dementia With Lewy Bodies
Depression
Frontal and Temporal Lobe Dementia
Vascular Dementia


Other Problems to Be Considered

Creutzfeldt-Jakob disease
Multiple system atrophy
Progressive supranuclear palsy


WORKUP

Laboratory Studies

* No specific tests are used for Parkinson disease dementia.

* Although findings are not useful for diagnostic purposes, associations with specific APOE e alleles have been variably found. Studies evaluating the role of the APOE4 allele have been inconclusive; a more recent and rigorously designed study found no association between APOE4 and Parkinson disease dementia.


Imaging Studies

* Structural imaging
- CT scanning and MRI do not help establish the diagnosis.
- As in Parkinson disease without dementia, patients with dementia may show decreased width of the pars compacta, decreased signal in the putamen, or both.

* Positron emission tomography
- Parkinson disease is associated with decreased uptake and retention of 18F-dihydroxyphenylalanine (18F-DOPA) in the basal ganglia.
- Reports of functional imaging in patients with Parkinson disease and cognitive impairment have been few. Some have shown changes similar to those observed in Alzheimer disease (asymmetrical decreased 18fluorodeoxyglucose-positron emission tomography [18FDG-PET] uptake on the parietal and posterior temporal regions) and others have not.
- Some studies of patients with Parkinson disease and either dementia or depression have demonstrated marked deficits in prefrontal activation and hypoperfusion in the superior temporal regions. The latter is more impaired in patients with Parkinson disease and dementia; the former, in patients with Parkinson disease and depression.


Histologic Findings

Parkinson disease is characterized by the death of a heterogeneous cell population, including neuromelanin-laden dopaminergic neurons of the substantia nigra pars compacta, aminergic brain nuclei, cholinergic neurons, neurons in the hypothalamus, and small cortical neurons (particularly in the cingulate gyrus and the entorhinal cortex).

Lewy bodies are found in the brainstem, basal forebrain, and cortex. In the first 2 regions, Lewy bodies are large, eosinophilic, hyaline inclusion bodies with clear halos and targetlike appearances. Cortical Lewy bodies are smaller and have less distinct cores.

A greater degree of medial nigral cell loss can result in more severe cognitive impairment. The degree of cognitive impairment also correlates with the density of Lewy neurites in the cornu ammonis 2 field of the hippocampus. Lewy neurites are degenerating, ubiquitin-positive neuronal processes or neurites that are different from Lewy bodies.

Senile plaques and neurofibrillary tangles are found in the cortices of patients with severe dementia, most prominently in their hippocampi. Other changes often include granulovacuolar degeneration and cortical cell loss.


TREATMENT

Medical Care

* Although no specific therapy exists for dementia, the American Academy of Neurology recently evaluated the evidence regarding the use of cholinesterase inhibitors in Parkinson disease dementia (Parkinson's disease dementia, PDD). Based on their review, they suggested that rivastigmine (US Food and Drug Administration approved for Parkinson disease dementia) and donepezil are probably effective in treating the dementia. The risk of potentially exacerbating motor symptoms may limit their widespread use.

* Focus treatment on managing the motor manifestations of Parkinson disease.

* Anticholinergic drugs used for the treatment of motor manifestations of Parkinson disease may exacerbate memory impairment. When possible, avoid these medications.


Psychiatric care

* Mood Disorders: For mood disorders, tricyclic agents, specifically the secondary amines (eg, nortriptyline, desipramine), heterocyclic agents, or serotonin reuptake inhibitors (SSRIs) are indicated.[2,10,11] In severe refractory cases, electroconvulsive therapy may be effective.[12] Psychotherapy can play an important role in the treatment of depression.[5] Limited evidence shows any benefit with dopamine agonists[13] and monoamine oxidase inhibitors[14] . A randomized, controlled trial reported by Menza et al determined that depression in patients with Parkinson disease may be responsive to treatment with nortriptyline.[15]

* Anxiety: SSRIs and venlafaxine can be beneficial. Buspirone is well tolerated, but has not been studied in this population. Benzodiazepines may help severe anxiety, but side effects such as cognitive impairment and balance problems may be concerning. Behavior modification techniques can play an important role in the treatment of anxiety.2,16

* Psychosis: Any medications that might contribute to psychosis must be first eliminated.[2] Medical conditions that may lead to psychosis must be treated.[12] Atypical antipsychotics are preferred. Clozapine is the agent of choice, but its use may be limited because of adverse effects. Quetiapine has not been tried extensively. Olanzapine and risperidone worsen motor function.[17] Dopamine agonists can lead to psychosis.[10] Limited evidence shows any benefit with cholinesterase inhibitors.[16,2]

* Sleep disturbances: Benzodiazepines can be helpful in the treatment of rapid eye movement sleep behavior disorder.[18] Obstructive sleep apnea can be treated with positive airway pressure with either continuous pressure or bi-level pressure.[18] Sleep hygiene techniques include avoiding stimulants/fluids near bedtime, avoiding heavy late-night meals, and following a regular sleep schedule.[16]

* Impulse control disorders: Because behaviors such as pathological gambling, hypersexuality, compulsive shopping, and binge eating may be related to the use of dopamine agonists, clinicians must closely monitor for such behaviors when using dopamine agonists. Doses may need to be decreased, or therapy may need to be completely discontinued.[16,11,12,2]


Surgical Care

Surgical treatment of Parkinson disease (eg, thalamotomy, pallidotomy, thalamic or subthalamic stimulation) improves some of the motor features of the disease but has no effect on cognitive deficits.


Consultations

The treatment of patients with Parkinson disease and dementia is best accomplished using a team approach.

* Motor manifestations, especially those that develop late in the course of the disease, are best managed by neurologists or internists experienced in the treatment of patients with dementia disorders.

* A psychiatrist who is familiar with the psychopharmacologic issues of Parkinson disease treatment should be part of the team, particularly when a mood disorder or psychosis complicates the course of illness.

* Physical therapists should work with the patient to ensure optimal neuromuscular fitness.

* A nutritionist can help ensure adequate energy intake, particularly when low-protein diets are needed to avoid adverse effects of levodopa.


Diet

Encourage patients to adopt a low-protein diet because such a diet may reduce fluctuations in dopamine levels.

Activity

Encourage patients to keep as active as possible. Recommend physical therapy to optimize motility.


MEDICATION

Various medications are used to treat the movement disorders of Parkinson disease, but these agents do not usually help the psychiatric symptoms of the disorder. In fact, they may worsen cognitive and psychiatric symptoms. Patients with Parkinson disease dementia respond to cholinesterase inhibitors, but improvement observed in any dementing disorder, given the products available currently, is neither dramatic nor permanent.


Centrally acting acetylcholinesterase inhibitors

Used to palliate cholinergic deficiency.

- Rivastigmine (Exelon)

Centrally acting inhibitor of AChE and BuChE.
US Food and Drug Administration approved for dementia of Parkinson's disease

Dosing

Adult
1.5 mg PO bid for 1 mo, then 3 mg PO bid for 1 mo, then 4.5 mg PO for 1 mo, and 6 mg PO bid thereafter; medication must be given with largest meals

Pediatric
Not established

Interactions
None reported; since drug metabolized by cholinesterases, no significant hepatic metabolism takes place

Contraindications
Documented hypersensitivity

Precautions
Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions
Administer with large meals to minimize adverse effects; always titrate upward slowly


- Donepezil (Aricept)

Centrally acting inhibitor of AchE but not of BuChE.

Dosing

Adult
5 mg PO qd for 3-4 wk, followed by 10 mg PO qd

Pediatric
Not established

Interactions
Increases effects of succinylcholine, cholinesterase inhibitors, or cholinergic agonists; may increase fluvoxamine levels

Contraindications
Documented hypersensitivity; sick sinus syndrome or other supraventricular cardiac conduction abnormalities; peptic ulcer disease; bladder outflow obstruction

Precautions

Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions
Caution in patients with seizures, asthma, sick sinus syndrome, or other supraventricular conduction abnormalities


- Galantamine (Razadyne, Razadyne ER)

Enhances central cholinergic function; likely to inhibit AChE.

Dosing

Adult
IR: 16-24 mg/d PO divided bid
ER: 16-24 mg PO qd

Pediatric
Not established

Interactions
Can interfere with effect of anticholinergic medications; synergistic effect if given concurrently with other ChEIs, succinylcholine, other neuromuscular blocking agents

Contraindications
Documented hypersensitivity

Precautions

Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions
Most frequent adverse events include nausea, vomiting, diarrhea, anorexia, and weight loss; dose titration needed in patients with hepatic and/or renal dysfunction; can cause bladder outflow obstruction; should be prescribed with care in patients with lung disease; could potentiate tendency toward seizures


- Rivastigmine transdermal patch (Exelon patch)

Competitive and reversible acetylcholinesterase inhibitor. While mechanism of action unknown, may reversibly inhibit cholinesterase, which may, in turn, increase concentrations of acetylcholine available for synaptic transmission in CNS and thereby enhance cholinergic function. Effect may lessen as disease process advances and fewer cholinergic neurons remain functionally intact.

Available as 5-cm2 patch containing 9 mg (releases 4.6 mg/24 h) and 10-cm2 patch containing 18 mg (releases 9.5 mg/24 h). Indicated for dementia of Alzheimer disease and for dementia associated with Parkinson disease.

Dosing

Adult
Apply patch to upper or lower back, upper arm, or chest
Initiating patch therapy (not switching from oral therapy): 4.6 mg/24 h patch (5 cm2) applied qd initially; if well tolerated and after minimum of 4 wk, increase to 9.5 mg/24 h patch (10 cm2) applied qd
Switching from oral administration to patch therapy:
Apply first patch on day following last oral dose
Total daily oral dose <6 mg/d: Switch to 4.6 mg/24 h patch
Total daily oral dose 6-12 mg/d: Switch to 9.5 mg/24 h patch

Pediatric
Not indicated

Interactions
May reduce effects of anticholinergics; increases effects of cholinergic agonists and neuromuscular blockers; risk of bradycardia increases when administered concurrently with beta-blockers without ISA, the calcium channel blockers diltiazem or verapamil, and digoxin

Contraindications
Documented hypersensitivity

Precautions

Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions
Apply patch to clean, dry, and hairless area of back, upper arm, or chest; area where patch is applied must be free of powder, oil, moisturizer, lotion, or other substances that would keep patch from adhering properly to skin; also, apply to areas free of cuts, rashes, or other irritation; may cause significant nausea, vomiting, anorexia, and weight loss if taken in doses higher than recommended; if significant adverse effects occur, patient should discontinue treatment for several doses, then restart at lowest dose; extrapyramidal symptoms may occur or be exacerbated (especially tremor); caution in history of peptic ulcer disease, sick sinus syndrome, urinary obstruction, pulmonary conditions (eg, COPD, asthma), and bradycardia or supraventricular conduction conditions


FOLLOW-UP

Further Outpatient Care

Patients with Parkinson disease must have regular follow-up care to ensure adequate treatment of motor and behavioral abnormalities. Once patients are stable on medications, provide follow-up care at least every 3-6 months and periodically adjust medication dosages as necessary.


Inpatient & Outpatient Medications

* Treatment of patients with Parkinson disease relies on the use of levodopa, dopamine agonists, monoamine oxidase type B (MAO-B) and catechol methyltransferase inhibitors, and anticholinergics.

* SSRIs and tricyclics are useful for the treatment of patients with depressive symptoms. MAO-B inhibitors contraindicate the use of many of these agents. Before starting any medication, possible interactions must be considered. MAO-B inhibitors contraindicate the use of many of these agents. Before starting any medication, possible interactions must be considered.


Deterrence/Prevention

To date, no strategy, method, treatment, or therapy prevents Parkinson disease and dementia.
Complications

* Patients with Parkinson disease and dementia with associated hallucinations are at high risk of dying within a few years of placement in care facilities.

* Psychotic states can develop as adverse effects of treatment with levodopa or, to a lesser extent, dopamine agonists.


Prognosis

Patients with Parkinson disease and dementia have a poorer prognosis than patients with Parkinson disease without dementia.


Patient Education

For excellent patient education resources, visit eMedicine's Dementia Center. Also, see eMedicine's patient education articles Parkinson Disease Dementia, Parkinson Disease, Dementia Medication Overview, and Alzheimer Disease.

Education for patients can include providing information about the disease process, prognosis, pharmacological interventions for symptoms, and nonpharmacological interventions such as psychotherapy for depression. Other educational topics can include driving safety, home safety, medication monitoring, advanced care planning, and possible assisted living or nursing home placement.

Education for caregivers can include a discussion about what may lie ahead for their loved one, respite care agencies, home health support/aid services, support through the American Parkinson Disease Association, advanced care planning, and safety issues.

Some Internet sites for the family education include the following:
* MayoClinic, Dementia: It's not always Alzheimer's
* WebMD, Tracking Dementia in Parkinson's Disease
* WebMD, FDA OKs Drug for Parkinson's Dementia


MISCELLANEOUS

Medicolegal Pitfalls
* Driving ability in patients with Parkinson disease must be assessed on an individual basis. Patients with prominent bradykinesia have difficulty moving the foot from the accelerator to the brake.
* Advise patients taking the non–ergot-derived dopamine agonists pramipexole and ropinirole not to drive or engage in hazardous activities because these medications produce sleep attacks.


REFERENCES

1. Lieberman AN. Point of view: Dementia in Parkinson's disease. Parkinsonism & Related Disorders. November 1997;3(3):151-158. [Medline].
2. Weintraub, D., Comella, C. L., & Horn, S. Parkinson's disease--Part 3: Neuropsychiatric symptoms. American Journal of Managed Care. 2008;14(2 Suppl):S59-S69. [Medline].
3. Lippa CF, Duda JE, Grossman M, Hurtig HI, Aarsland D, Boeve BF, et al. DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology. Mar 13 2007;68(11):812-9. [Medline].
4. Goldmann Gross, R., Siderowf, A., & Hurtig, H. I. Cognitive impairment in Parkinson's disease and dementia with lewy bodies: a spectrum of disease. Neuro-Signals. 2008;16(1):24-34. [Medline].
5. Frisina PG, Borod JC, Foldi NS, Tenenbaum HR. Depression in Parkinson's disease: Health risks, etiology, and treatment options. Neuropsychiatr Dis Treat. February 2008;4(1):81-91. [Medline].
6. Galvin JE, Pollack J, Morris JC. Clinical phenotype of Parkinson disease dementia. Neurology. Nov 14 2006;67(9):1605-11. [Medline].
7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington DC: American Psychiatric Association; 2000.
8. Wolters, E. C. Variability in the clinical expression of Parkinson's disease. Journal of the neurological sciences. March 2008;266(1-2):197-203. [Medline].
9. Jankovic, J. Parkinson's disease: clinical features and diagnosis. Journal of neurology, neurosurgery, and psychiatry. April 2008;79(4):368-376. [Medline].
10. Chan, D. K., Cordato, D. J., & O'Rourke, F. Management for motor and non-motor complications in late Parkinson's disease. Geriatrics. May 2008;63(5):22-27. [Medline].
11. Borek, L. L., Chou, K. L., & Friedman, J. H. Management of the behavioral aspects of Parkinson's disease. Expert review of neurotherapeutics. June 2007;7(6):711-725. [Medline].
12. Truong, D. D., Bhidayasiri, R., & Wolters, E. Management of non-motor symptoms in advanced Parkinson disease. Journal of the neurological sciences. March 2008;266(1-2):216-228. [Medline].
13. Ziemssen, T., & Reichmann, H. Non-motor dysfunction in Parkinson's disease. Parkinsonism & related disorders. August 2007;13(6):323-332. [Medline].
14. Barbas, N. R. Cognitive, affective, and psychiatric features of Parkinson's disease. Clinics in geriatric medicine. November 2006;22(4):773-796, v-vi. [Medline].
15. [Best Evidence] Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Buyske S, et al. A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology. Mar 10 2009;72(10):886-92. [Medline].
16. Ferreri, F., Agbokou, C., & Gauthier, S. Recognition and management of neuropsychiatric complications in Parkinson's disease. Canadian Medical Association journal. December 2006;175(12):1545-1552. [Medline].
17. Rongve, A., & Aarsland, D. Management of Parkinson's disease dementia : practical considerations. Drugs & aging. 2006;23(10):807-822. [Medline].
18. Friedman, J. H., & Millman, R. P. Sleep disturbances and Parkinson's disease. CNS Spectrums. March 2008;13:3 (Suppl 4):12-17. [Medline].
19. Aarsland D, Zaccai J, Brayne C. A systematic review of prevalence studies of dementia in Parkinson's disease. Mov Disord. Oct 2005;20(10):1255-63. [Medline].
20. Cummings JL. Frontal-subcortical circuits and human behavior. Arch Neurol. Aug 1993;50(8):873-80. [Medline].
21. Cummings JL, Darkins A, Mendez M, Hill MA, Benson DF. Alzheimer's disease and Parkinson's disease: comparison of speech and language alterations. Neurology. May 1988;38(5):680-4. [Medline].
22. Cummings JL, Huber SJ. Visuospatial abnormalities in Parkinson's disease. In: Huber SJ, Cummings JL, eds. Parkinson's Disease: Neurobehavioral Aspects. New York, NY: Oxford University Press; 1992:59-73.
23. Ebmeier KP, Calder SA, Crawford JR, Stewart L, Besson JA, Mutch WJ. Clinical features predicting dementia in idiopathic Parkinson's disease: a follow-up study. Neurology. Aug 1990;40(8):1222-4. [Medline].
24. Goetz CG, Blasucci LM, Leurgans S, Pappert EJ. Olanzapine and clozapine: comparative effects on motor function in hallucinating PD patients. Neurology. Sep 26 2000;55(6):789-94. [Medline].
25. Harhangi BS, de Rijk MC, van Duijn CM, et al. APOE and the risk of PD with or without dementia in a population-based study. Neurology. Mar 28 2000;54(6):1272-6. [Medline].
26. Jasinska-Myga B, Opala G, Goetz CG, Tustanowski J, Ochudlo S, Gorzkowska A, et al. Apolipoprotein E gene polymorphism, total plasma cholesterol level, and Parkinson disease dementia. Arch Neurol. Feb 2007;64(2):261-5. [Medline].
27. Levy ML, Cummings JL, Fairbanks LA, et al. Apathy is not depression. J Neuropsychiatry Clin Neurosci. Summer 1998;10(3):314-9. [Medline].
28. Marder K, Tang MX, Cote L, Stern Y, Mayeux R. The frequency and associated risk factors for dementia in patients with Parkinson's disease. Arch Neurol. Jul 1995;52(7):695-701. [Medline].
29. Mayeux R. Parkinson's disease: A review of cognitive and psychiatric disorders. Neuropsychiatr Neuropsychol Behav Neurol. 1990;3:3-14.
30. Mayeux R, Denaro J, Hemenegildo N, Marder K, Tang MX, Cote LJ, et al. A population-based investigation of Parkinson's disease with and without dementia. Relationship to age and gender. Arch Neurol. May 1992;49(5):492-7. [Medline].
31. Miyasaki JM. New practice parameters in Parkinson's disease. Nat Clin Pract Neurol. Dec 2006;2(12):638-9. [Medline].
32. Perl DP, Olanow CW, Calne D. Alzheimer's disease and Parkinson's disease: distinct entities or extremes of a spectrum of neurodegeneration?. Ann Neurol. Sep 1998;44(3 Suppl 1):S19-31. [Medline].
33. Raskin SA, Borod JC, Tweedy J. Neuropsychological aspects of Parkinson's disease. Neuropsychol Rev. Sep 1990;1(3):185-221. [Medline].
34. Stern Y, Marder K, Tang MX, Mayeux R. Antecedent clinical features associated with dementia in Parkinson's disease. Neurology. Sep 1993;43(9):1690-2. [Medline].


KEYWORDS

Parkinson disease, PD, Parkinson's disease, parkinsonism, Alzheimer disease, AD, Alzheimer's disease, dementia, senility, palsy, cognitive deficits, cognitive impairment, cognitive dysfunction, neurodegenerative disorders


CONTRIBUTING INFORMATION AND DISCLOSURES

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
Margaret M Swanberg, DO is a member of the following medical societies: American Academy of Neurology and American Neuropsychiatric Association
Disclosure: Nothing to disclose.

Coauthor(s)

Raj K Kalapatapu, MD, Fellow in Geriatric Psychiatry, Mount Sinai School of Medicine
Raj K Kalapatapu, MD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Association for Geriatric Psychiatry, American Medical Association, and American Psychiatric Association
Disclosure: Nothing to disclose.

Medical Editor

Alan D Schmetzer, MD, Professor, Vice-Chair for Education, and Director of Residency Training in General and Addiction Psychiatry, Department of Psychiatry, Indiana University School of Medicine
Alan D Schmetzer, MD is a member of the following medical societies: American Academy of Addiction Psychiatry, American Academy of Clinical Psychiatrists, American Academy of Psychiatry and the Law, American College of Physician Executives, American Medical Association, American Neuropsychiatric Association, American Psychiatric Association, and Association for Convulsive Therapy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Iqbal Ahmed, MBBS, Professor, Department of Psychiatry, John A Burns School of Medicine, University of Hawaii
Iqbal Ahmed, MBBS is a member of the following medical societies: Academy of Psychosomatic Medicine, American Association for Geriatric Psychiatry, American Neuropsychiatric Association, and American Psychiatric Association
Disclosure: Nothing to disclose.

CME Editor

Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry and Department of Medicine, Froedtert Hospital, Medical College of Wisconsin
Harold H Harsch, MD is a member of the following medical societies: American Psychiatric Association
Disclosure: lilly Honoraria Speaking and teaching; Forest Labs Honoraria Speaking and teaching; AstraZeneca Honoraria Speaking and teaching; Pfizer Grant/research funds Speaking and teaching; Northstar Grant/research funds Research; Novartis Grant/research funds research; Pfizer Speaking and teaching; Sanofi-avetis Grant/research funds research; Otsuke Grant/research funds reseach; GlaxoSmithKline Grant/research funds research

Chief Editor

Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA
Stephen Soreff, MD is a member of the following medical societies: American College of Mental Health Administration and American Psychosomatic Society
Disclosure: Nothing to disclose.
Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Jose G Merino, MD to the development and writing of this article.


FURTHER READING

Books

"What If It’s Not Alzheimer’s? A Caregiver’s Guide to Dementia"
"Practical Dementia Care"

Web sites

American Parkinson Disease Association
NIH Senior Health – Parkinson’s Disease
NINDS – Parkinson’s Disease
American Association for Geriatric Psychiatry – Position Statements
American Psychiatric Association – Practice Guideline for the Treatment of Patient’s with Alzheimer’s Disease and Other Dementias

Caregiver Resources

Family Caregiver Alliance
Eldercare

Other Resources for Patients with Dementia

American Medical Association – Physician’s Guide to Assessing and Counseling Older Adult Drivers
MedicAlert and Safe Return
NINDS – Dementia: Hope Through Research

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Updated: Apr 15, 2009