I. What is Parkinson’s disease dementia? Parkinson’s disease with dementia (PDD) is dementia that is directly caused by the pathological changes of Parkinson’s disease. It is characterized by slowly progressive cognitive impairment that occurs one or more years after the onset of PD and that affects the patient’s ability to perform daily living activities. Zhou Aijong, Department of Neurology, Xuanwu Hospital, Capital Medical University Second, do all patients with Parkinson’s disease have dementia? According to statistics, the prevalence of dementia among Parkinson’s disease patients is about 20% to 40%, which is four to six times higher than that of the general population. The average time from onset of Parkinson’s disease to dementia is about 10 years, but there are significant differences between individuals. Patients who are male, of advanced age, with low education, poor economic standard of living, with long duration of disease, with a high degree of Parkinson’s disease, with early cognitive impairment, and with early depression or psychiatric abnormalities are prone to develop dementia. The clinical manifestations are predominantly motor retardation and postural or gait disorders, which are prone to dementia, while those with predominantly tremors are less likely to develop dementia. Third, what are the clinical manifestations of Parkinson’s disease dementia? The clinical manifestations of PDD include symptoms of dyskinesia, fluctuating cognitive dysfunction and psychiatric symptoms of Parkinson’s disease. 1. motor impairment Motor symptoms in patients with PDD are mainly postural instability, gait disturbance, motor retardation, and less tremor. Moreover, motor symptoms are less effective to dopa-like drug treatment and are prone to hallucinations and other adverse effects. Cognitive dysfunction in PDD is mainly manifested by decreased attention (fluctuating, diminished attention and decreased alertness), decreased executive ability (decreased initiation, organization, planning, abstract generalization, etc.), slowed psychomotor speed (delayed perception, analysis and processing of information), abnormal visual-spatial discrimination skills (decreased visual discrimination, object shape discrimination and spatial structure, etc.), memory (the patient is unable to recall things on his or her own, but is given cues to help recall). The patient’s speech is slow and low, but language function (the ability to understand, name, repeat, read, and read books) and orientation (the ability to recognize time, place, and person identity) are relatively preserved. 3. Psychiatric symptoms In addition to cognitive dysfunction, patients with PDD may exhibit a variety of other psychiatric symptoms, including apathy, depression, anxiety, sleep disturbances (insomnia, increased daytime sleep, rapid eye movement phase sleep behavior disorder), agitation, restlessness, delirium, and visual hallucinations. Fourth, how to diagnose Parkinson’s disease dementia? The diagnosis of PDD must be based on a confirmed diagnosis of PD, which can be briefly summarized as follows: ① the patient meets the criteria for primary Parkinson’s disease; ② cognitive impairment occurs after the motor symptoms of Parkinson’s disease, and the patient develops slowly progressive cognitive impairment one or several years after the onset of Parkinson’s disease; ③ cognitive impairment hinders his or her ability to work or live (such as work, social interaction, domestic ability, etc.); ④ exclude other causes of dementia or mental disorders (such as cerebrovascular disease, other brain degenerative diseases, hydrocephalus, vitamin deficiency, drug-induced mental retardation, delirium, etc.). V. What is the difference between Parkinson’s disease dementia and other common types of dementia? Alzheimer’s disease (AD), commonly known as “senile dementia” in China, is the most common cause of dementia, accounting for about 2/3 of all patients with dementia. The main difference between the two is that AD patients have dementia as the main manifestation, and motor impairment usually appears in the middle and late stages of the disease, while PDD patients, on the contrary, have significant motor impairment first and cognitive impairment only in the middle and late stages of the disease. Another major difference is that AD is highlighted by memory storage impairment, suggesting that without help, patients present early with impaired time and place recognition and gradually progress to full-blown dementia. In contrast, patients with PDD have relatively normal early memory storage and time-place orientation abilities. 2. Vascular dementia Vascular dementia is dementia caused by brain damage due to ischemic or hemorrhagic cerebrovascular disease, and is the second most important type of dementia in the elderly. Patients mostly have a history of stroke, and there is a clear temporal relationship between cognitive impairment and stroke, with clear stroke lesions on brain imaging. However, patients with lacunar status (very large number of small lacunar infarcts in the brain) or severe white matter lesions can present clinically with Parkinson’s syndrome and cognitive impairment without a clear history of stroke and can be misdiagnosed as PDD, requiring specialized differentiation. 3. dementia with Lewy bodies (DLB) Dementia with Lewy bodies shares a common pathology (Lewy bodies) with Parkinson’s disease and has some similarities in clinical manifestations, including motor symptoms, fluctuating cognitive deficits and visual hallucinations similar to Parkinson’s disease. However, compared with Parkinson’s disease, the cognitive impairment in DLB appears early and prominent, while the motor impairment is relatively mild, slow in progression, and mostly bilaterally symmetrical (while Parkinson’s mostly starts unilaterally and progresses to the contralateral limb in an N-shaped pattern over time, and the motor impairment continues to progress). Currently, the “1-year principle” is used as the differential diagnosis: if dementia occurs more than 1 year after the onset of extrapyramidal motor symptoms, the diagnosis of PDD is preferred; if dementia precedes motor symptoms, or if dementia occurs within 1 year after the onset of motor symptoms, the diagnosis of DLB is preferred. VI. Parkinson’s disease How is dementia treated? The treatment of PDD includes 3 aspects: 1. Treatment of movement disorders The treatment principles for extrapyramidal symptoms in patients with PDD are the same as those for primary PD, and dopamine drugs remain the first-line treatment drugs. Amantadine and dopamine receptor agonists are not included in the first-line treatment of PDD because they tend to cause psychiatric symptoms such as hallucinations. Anticholinergics (e.g., benzodiazepines) are cognitively damaging and should be avoided in patients with PDD. 2. treatment of cognitive impairment PDD patients with intracerebral cholinergic deficiency, cholinesterase inhibitors can increase intracerebral acetylcholine levels, cholinesterase inhibitors cabalactam and donepezil are currently the main drugs for PDD treatment. The therapeutic doses are 6-12 mg/day and 5-10 mg/day, respectively, and should be increased slowly from the smallest dose to the therapeutic dose. The main adverse effects are gastrointestinal symptoms such as nausea, vomiting and diarrhea, and some patients may have mild exacerbation of tremor symptoms, but no significant exacerbation of other extrapyramidal symptoms. Studies in small samples suggest that the excitatory amino acid receptor antagonist meperidine can improve the overall function of patients with PDD at a therapeutic dose of 10 to 20 mg/day. When patients with PDD develop psychotic symptoms such as hallucinations and delusions, the dose of benzhexol, amantadine, dopamine agonists and monoamine oxidase-B (MAO-B) inhibitors should be reduced or discontinued sequentially; if the symptoms still do not improve, levodopa should be gradually reduced; the cholinesterase inhibitors carbaplatin and donepezil can also improve PDD’s hallucinations, delusions, apathy, and anxiety; if the above treatments still do not relieve the symptoms, then atypical antipsychotics (clozapine or quetiapine) with few extravertebral side effects are chosen. The greatest side effect of clozapine is granulocytopenia, and patients taking this drug should have their absolute granulocyte values rechecked regularly. Both of these medications should be started in small doses and aimed at the smallest possible dose for optimal efficacy. Other atypical antipsychotics, such as risperidone (fispefidone) and olanzapine (olanzapine), can aggravate extrapyramidal symptoms and are therefore not recommended for the treatment of psychiatric symptoms in PDD. PDD patients often have depression and anxiety. Selective 5-hydroxytryptamine reuptake inhibitors (SSRI) have milder side effects and are currently the drug of choice for PDD patients with depressive or anxiety symptoms, with 6-12 weeks of initial treatment and 4-9 months of maintenance treatment, with close observation for possible complications. References: Chinese Society of Neurology, Parkinson’s Disease and Movement Disorders Group, Chinese Society of Neurology, Neuropsychology and Behavioral Neurology Group. Guidelines for the diagnosis and treatment of dementia in Parkinson’s disease. Chinese Journal of Neurology. 2011, 44(9): 635-637. Chen Xiaochun, Pan Xiaodong. Diagnosis and treatment of dementia in Parkinson’s disease. 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