Late non-motor complications

Dementia In PD, dementia occurs late and may present as frontal dysfunction (dysexecutive syndrome affecting attention, planning, etc.), visuospatial disorientation, and memory impairment. A randomized controlled trial has shown a modest effect of rivastigmine in an older population (mean age, 73±7) with improvement of cognitive function and AD Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC). At 6 months, the difference between the treatment group and placebo was 1 point for the mini-mental state examination (MMSE) score and was 2.8 points for the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score.¹⁶ Improvement in MMSE and Caregiver Interview-Based Impression of Change scores was also found with donepezil compared to placebo in a small study.¹⁷ A theoretical concern exists, however, that the cholinergic system antagonizes the dopaminergic system (eg, acetylcholinesterase inhibitor worsening of tremor).

The incidence of dementia may be as high as 6-fold in PD patients and is associated with age, presence of severe motor symptoms or atypical neurologic features, depression, and early occurrence of levodopa-related confusion or psychosis.^18,19 Patients with the most rapid progression of parkinsonian motor symptoms have also been shown to be up to 8 times more likely to develop Alzheimer's disease, suggesting a possible common pathologic process, such as the abnormal deposition of proteins like beta-amyloid and alpha-synuclein.^20-22

Randomized controlled trials have shown clozapine to be useful in treating psychosis.^23,24 Nevertheless, concern about an adverse reaction of agranulocytosis and therefore the need for regular monitoring of blood count has made this agent less appealing. Quetiapine has been used as an alternative, although high-level randomized controlled trial data are still lacking. Both olanzapine and risperidone should be avoided or used with caution as these agents may worsen motor symptoms. Older neuroleptic agents such as haloperidol are to be avoided because of significant extrapyramidal side effects. There is low-level evidence to suggest that acetylcholinesterase inhibitors can improve symptoms of psychosis, but these claims have not been tested in randomized controlled studies.

Postural hypotension This is a common problem in late PD and occurs in 15% to 20% of cases. Both dopamine agonists and L-dopa can aggravate postural hypotension. Management includes lowering the dosage of dopamine agonists or L-dopa but at a cost of worsening motor symptoms. Furthermore, other drugs the patient may be taking that could exacerbate the problem (ie, antihypertensives and diuretics) should be reviewed. If neither of these is an option, the addition of fludrocortisone, 0.1 mg/d, or the use of midodrine can be considered, but supine hypertension and fluid retention may be unwanted side effects. If isolated systolic hypertension and significant postural drop of BP coexist in the same patient, the use of pindolol, a nonselective beta blocker with partial agonist activity, can be tried, commencing at 2.5 mg daily.

Acetylcholinesterase inhibition with the older agent pyridostigmine may improve standing BP without inducing supine hypertension. However, use of this agent may result in worsening tremor.²⁵

Falls Postural hypotension is an important causative factor of falls in PD patients. Its management is discussed previously herein.

Table 2 Remember the mnemonic AEIOU, BBC