The Treatment of Older Patients with Parkinson’s Disease

Abstract

Background

There are approximately 150 000 persons over age 80 in Germany who suffer from Parkinson’s disease. Eighty percent of patients develop dementia during the course of this disease. Older patients with Parkinson‘s disease often suffer from the multimorbidity typically seen in this age group. Comorbidities affect the options for treating Parkinson’s disease. Older patients are markedly underrepresented in most trials of antiparkinsonian drugs.

Methods

In this narrative review, we propose practical ways to simplify the treatment regimen of older patients with Parkinson‘s disease to lessen side effects and make treatment more manageable for these patients and the persons caring for them.

Results

The mainstay of treatment is levodopa in combination with a dopa decarboxylase inhibitor, taken during the day as a standard-release or dispersible formulation and at night in extended-release form; along with a catechol-O-methyltransferase inhibitor if necessary. Antiparkinsonian drugs with other mechanisms of action should be used sparingly, if at all. Treatment options for patients with severe fluctuations in efficacy and long “off” (akinetic) phases include a jejunal levodopa pump and the subcutaneous administration of foslevodopa. Parkinson’s disease dementia should be treated with rivastigmine, a cholinergic anti-dementia drug (approved in capsule form for this indication). Otherwise intractable psychosis should be treated with quetiapine (off-label) or clozapine (evidence-based; weekly blood tests required). Other neuroleptic drugs should not be given to patients with Parkinson‘s disease. Physiotherapy and speech therapy are evidence-based components of therapy with proven efficacy in every stage of the disease.

Conclusion

Further randomized controlled trials tailored to this patient population are needed to provide a better evidence base for the treatment of older patients with Parkinson‘s disease.

Information about this CME

This article has been certified by the North Rhine Academy for Continuing Medical Education. The questions on this article may be found (in German) at http://daebl.de/RY95 (Deutsches Ärzteblatt’s CME portal). Their English translation may be found in the PDF version of this article. The closing date for entries is July 24, 2026.

Participation is possible at: cme.aerzteblatt.de

Parkinson’s disease is characterized by a reduction and slowness of movement (bradykinesia) and at least one other symptom (resting tremor or rigor) (eTable). Geriatric patients are defined by an advanced age (predominantly 70 years and older) and the multimorbidity typically seen in this age group or by an age of 80 and older with an age-related increased vulnerability (e1). Geriatric treatment is provided to Parkinson patients whose illness began many years previously and who have therefore reached an advanced stage of the disease, as well as to patients who are diagnosed for the first time at an advanced age.

eTable. Common Parkinson’s syndromes in older patients.

Syndrome	Symptoms	Response to levodopa	cMRI	Pathology	Synonyms and subtypes
Parkinson’s disease	Bradykinesia, rigidity (rigor), tremor (asymmetric)	++++	Normal	Alpha-synuclein	Maladie de Parkinson, idiopathic Parkinson’s syndrome, shaking palsy
Dementia with Lewy bodies	Cognitive impairment and EPMS	++(+)		Alpha-synuclein	Lewy body dementia
Vascular parkinsonism	Often general slowness and gait disorder	++	High vascular lesion load or strategic infarctions, e.g., of the basal ganglia	Ischemic
Drug-induced parkinsonism	Tremor, rigor, bradykinesia	Treatment: stop the offending medication	Normal	None	Caused by neuroleptics, metoclopramide, valproic acid, rarely other drugs (e24)
Multiple system atrophy (MSA)	EPMS and autonomic dysfunction	+	Hot cross bun sign	Alpha-synuclein	MSA-C (cerebellar)MSA-P (parkinsonion type)
Progressive supranuclear palsy	EPMS and gaze palsy, early balance dysfunction and falls, cognitive impairment	+	Hummingbird signMickey mouse sign	Tauopathy	Steele-Richardson-Olszewski syndrome
Normal pressure hydrocephalus	Hakim’s triad (gait disturbances, cognitive disturbances, and urinary incontinence)	-	Typically already visible on cCT: steep callosal angle < 90°, tight convexity, evans index >0.3

cCT, cranial computed tomography; cMRI, cranial magnetic resonance imaging; EPMS, extrapyramidal motor symptoms; MSA, multiple system atrophy

Disease prevalence increases with age (men/women between the ages of 80 and 84 2.86/2.02%, between 85 and 89 years 3.64/2.59%, and 90 years and older 3.92/2.57%). A total of around 310 000 individuals in Germany are affected by the illness, of which around 150 000 are aged 80 and older (e2).

Approximately 60% of patients in whom the diagnosis of Parkinson’s is made for the first time after reaching the age of 80 suffer from the akinetic-rigid phenotype. Parkinson’s symptoms, especially postural instability, is exacerbated by comorbidities common in old age, in particular polyneuropathy, disorders of vision, inner ear diseases, and sarcopenia (1, 2). The prevalence of orthostatic hypotension correlates with age. Pain, constipation, sleep disorders, and disturbed bladder function secondary to Parkinson’s disease are exacerbated by multimorbidity. Neuropsychiatric symptoms, such as apathy, depression, and anxiety are symptoms of Parkinson’s disease, but also occur frequently independent of it in older age. Around 80% of patients develop dementia in the course of the disease (3, 4, e3). A large number of elderly patients with Parkinson’s disease receive polypharmacy (≥ 5 prescription drugs) or hyperpolypharmacy ((≥ 10 prescription drugs) (e4).

With increasing duration of the disease, serious impairments are to be expected from the side effects of Parkinson’s medication and the disease itself, for example, daytime fatigue, obsessive-compulsive disorder, confusion, or predominantly optic hallucinations. Fluctuations in drug action become increasingly uncontrollable. Orthostatic hypotension and disorientation, delusions, and visual hallucinations are not just related to high drug dosages (5). Around 50% of patients with Parkinson’s disease report present or previous hallucinations (5), while daytime fatigue and orthostatic hypotension are even more common (2).

Methods

The aim of the present narrative review is to summarize the available forms of treatment for Parkinson’s disease in the specific context of older patients. We conducted a search of the literature in PubMed using the search terms “parkinson’s disease” and “randomized trial” and “old age” (n = 41) or “geriatric” (n = 198) as well as the search terms “parkinson’s disease” and “old age” or “geriatric” together with individual drug names. We also looked at the pharmacokinetics and dynamics of the drugs used to treat Parkinson’s disease, with a focus on the special features related to old age. The search terms were individual drug names and “pharmacokinetics” and “old age” or “geriatric”. Currently, there is a paucity of randomized controlled trials covering more evidence-based treatment of older patients with Parkinson’s disease (e5).

Pharmacologic therapy with levodopa

Tables 1–3 and the Figure provide an overview of the drugs available for the treatment of Parkinson’s disease, their pharmacokinetics, and randomized trials.

Table 1. Overview of available treatment (sources are respective professional drug information, retrieved on October 27, 2024).

Classes	Substances	Usual dose per day	Maximum daily dose	Elimination half-life	Specific side effects
Levodopa	Soluble levodopa, levodopa Extended-release levodopa Levodopa-carbidopa intestinal gel (LCIG)*2 Foslevodopa SC	150–800 mg 100–200 mg 40–80 mg/h (2–4 mL/h) 36–96 mg/h (0.15–0.3 mL/h)	1200 mg (rarely more)*1 200 mL = 4000 mg levodopa 6000 mg (= 4260 mg levodopa)	1.5 h younger 1.8 h older pats.	Hypotension Hallucinations Confusion Psychosis
Decarboxylase inhibitors (fixed-dose combination with levodopa)	Benserazide Carbidopa	¼ of the levodopa dose		1.5 h 7.7–11.7 h	Intolerance, e.g., gastrointestinal symptoms
COMT inhibitors	Entacapone Opicapone Tolcapone	200 mg with each levodopa dose 25–50 mg/d 3-times 100 mg/d	2 g 50 mg 600 mg	0.4–2.5 h 0.7–3.2 h 2 h	Levodopa side effects increased Liver toxicity from tolcapone
Dopamine agonists	Extended-release Pramipexole Ropinirole Piribedil Transdermal rotigotine Apomorphine Apomorphine SC	0.26–3.15 mg/d 2–8 mg/d 150–250 mg 2–8 mg 1–4 mg/h	3.15 mg/d 24 mg 250 mg 16 mg 100 mg	8 h younger, 12 h older pats. 6 h 12 h 2–3 h 0.5 h	In addition to those mentioned for levodopa: impulse control disorders, stereotyped behavior (punding), microsleep, hallucinations
MAO inhibitors	Selegiline Rasagiline Safinamide	5–10 mg 1 mg 50–100 mg	10 mg 1 mg 100 mg	1.7 h 0.6–2 h 20–30 h	In addition to those mentioned for levodopa: hypertension, serotonin syndrome
NMDA receptor antagonist	Amantadine	100–300 mg	600 mg	10–30 h	In addition to those mentioned for levodopa: cardiac arrhythmia, urinary retention, toxicity secondary to kidney failure

*¹ Doses over 800 mg are not covered in the drug information of most manufacturers and therefore constitute a prescription outside the use approved by the drug regulatory authorities (off-label use).

*² Levodopa-carbidopa intestinal gel, also available in fixed combination with entacapone (LECIG)

(maximum recommended daily dose 2000 mg levodopa, 500 mg carbidopa monohydrate and 2000 mg entacapone)

COMT, catechol-O-methyltransferase inhibitors; MAO, monoamine oxidase inhibitors; NMDA, N-methyl-D-aspartate; pats., patients; SC, subcutaneous

Table 3. Randomized clinical trials on the pharmacotherapeutic treatment of older patients with Parkinson’s disease.

Author, reference	Age of the included pats. in years (mean), measure of spread	Intervention	Primary outcome	Comments
Ferreira 24	64 ± 9 (SD)	5, 25 or 50 mg opicapone once daily versus placebo or entacapone (200 mg with each dose of levodopa)	Opicapone 50 mg was more effective than placebo (mean difference 60.8 min less akinesia, 95% CI [97.2 min; 24.4 min]; p = 0.0015) and not inferior to entacapone (reduction of mean akinesia duration by 26.2 min; 95% CI reduction by 63.8 min to increase by 11.4 min; p = 0.0051)	Most common side effects: dyskinesia and constipation; no red discoloration of urine with opicapone; 5 and 25 mg opicapone not effective
Poewe e8	64 ± 8 63 ± 8 61 ± 10 66 ± 9 63 ± 9 Meta-analysis	Entacapone (200 mg with each dose of levodopa)	Entacapone increased on-time by 0.7 to 1.6 h per day (MV; p <0.01 or 0.05 in all 5 trials)	Improved quality of life with entacapone; most common side effects: dyskinesia, red discoloration of urine; combination tablet with levodopa/carbidopa
Soileau 29	66 ± 10	Foslevodopa plus foscarbidopa subcutaneous versus oral levodopa plus carbidopa	Mean increase in on-time without troublesome dyskinesia per day by 1.75 h ([0.46 h; 3.05 h]; p = 0.0083)	Side effects, in particular after subcutaneous infusion: redness, pain, cellulitis, local edema, infection of injection site
Graye 11	73 ± 8	Additional treatment with dopamine agonist, MAO-B inhibitor, or COMT inhibitor for hypokinesia not satisfactorily treated with levodopa	Patient-rated quality of life (PDQ-39) better with MAO-B inhibitors as adjuvant treatment than with COMT inhibitors (difference of the PDQ-39 mobility score 4.2 points ([0.4; 7.9]; p = 0.003)	No statistically significant differences between dopamine agonists and MAO-B or COMT inhibitors; study not blinded; free selection of the drug within the randomized substance class; drop-out rate due to discontinuation in 50% (COMT inhibitor), 56 % (dopamine agonist) and 61% (MAO-B inhibitor)
Friedman 32	71 ± 9 (verum) 72 ± 8 (placebo)	Clozapine versus placebo	Clozapine 6.25–50 mg/d reduced hallucinations without worsening motor symptoms (mean change of CGI by −1.6 ± 0.03 versus 0.5 ± 0.02 (MV ± SD; p <0.001)	Positive effect of clozapine on tremor; side effects: accelerated pulse, one case of leukopenia
French Study Group 33	72 ± 8	Clozapine versus placebo	Clozapine 6.25–50 mg/d reduced hallucinations with no lasting worsening of motor symptoms (significant change of CGI and PANSS Positive Subscore; p = 0.001 and <0.001)	Side effects: somnolence, temporary deterioration of mobility, no agranulocytosis
Pollak 34	71 ± 7 (verum) 73 ± 8 (placebo)	Clozapine versus placebo	Clozapine 6.25–50 mg/d reduced delusions and hallucinations with no permanent worsening of motor symptoms (median variation of CGI by –2.2 ([-2.6; –1.8], p <0.0001)	Side effects: somnolence, 2 cases of neutropenia, 1 case of seizures >50% of pats. no longer had hallucinations or delusions with clozapine
Tariot e43	75 ± 8	Pimavanserin versus placebo in pats. with psychosis related to Alzheimer’s and Parkinson’s disease and other dementias	Psychosis relapse in 12 of 95 (13%) pats. in the verum group and 28 of 99 (28%) in the placebo group (hazard ratio 0.35; [0.17; 0.73]; p = 0.005)	15.1% of pats. had Parkinson’s disease dementia, 7.1% dementia with Lewy bodies; pimavanserin is approved in the USA but not in the European Union.
Emre 35	73 ± 7 (verum) 72 ± 6 (placebo)	Rivastigmine PO versus placebo in Parkinson’s pats. with dementia	Rivastigmine improved cognition to a clinically significant degree (improvement of the ADAS-Cog score by 2.1 ± 8.2 versus worsening by 0.7 ± 7.5 points; p <0.001).	Rivastigmine reduced hallucinations and orthostatic dysregulation; increased incidence of nausea, vomiting, diarrhea, and tremor on rivastigmine
Henderson 38	71 (range 54–90) verum 69 (range 46–88) placebo	Rivastigmine PO versus placebo in Parkinson’s pats. without dementia	Rivastigmine improved step time variability for normal walking (ratio of geometric means 0.72; [0.58; 0.88]; p = 0.002) and during simple dual task (0.79; [0.62; 0.99], p = 0.045)	Rivastigmine reduced the incidence of falls from 2.4/month to 1.4/month (secondary endpoint: adjusted difference 0.55; [0.38; 0.81], p = 0.002); increased nausea and vomiting on rivastigmine; primary trial endpoint not significantly different

Older patients are usually excluded from the majority of randomized controlled drug trials.

One decisive reason is their relatively high mortality and high rate of complications possibly associated with the respective study medication.

The Table includes those studies whose results are, in our opinion, applicable to older patients.

Various randomized trials with different age groups document the benefit of physiotherapy, occupational therapy, speech therapy (7), bright light therapy, transcranial magnetic stimulation, and complex interventions (eSupplement).

ADAS-Cog, Alzheimer‘s Disease Assessment Scale Cognitive Subscale; CGI, Clinical Global Impression Scale; COMT, catechol-O-methyltransferase;

CI, confidence interval; MAO-B, monoamine oxidase B; MV, mean value; PANSS, Positive and Negative Syndrome Scale; pats.; patients;

PDQ-39, Parkinson’s Disease Questionnaire-39; PO, oral; SD, standard deviation

Figure.

Effect/side effect ratio of various groups of anti-Parkinson’s medications This ratio is most favorable for levodopa, followed by catechol-O-methyltransferase inhibitors.

We would like to thank Prof. Martin Wehling for his permission to modify the Figure depicted in his book (6).

Levodopa

The amino acid levodopa is only used in combination with a decarboxylase inhibitor (benserazide or carbidopa) because otherwise it is subject to rapid metabolization. Such combinations have the most favorable effect/side effect ratio, regardless of patient age. Because levodopa-induced dyskinesia can develop after about five years, an attempt to first start with less effective drugs is made in younger patients. This risk is accepted when treating older patients (6, 7).

Pharmacokinetics

The elimination half-life (t½) of a single oral dose of levodopa administered together with a decarboxylase inhibitor is around 1.8 hours in older patients (8). The pharmacokinetics of levodopa is influenced by gastric emptying which can be delayed in Parkinson’s disease (9). The time to reach peak plasma concentration of levodopa after oral administration varies interindividually and intraindividually and ranges between 0.5 and two hours (8).

Levodopa doses taken together with a (protein-rich) meal may be less effective (protein akinesia) (10, 11, 12). The person undergoing treatment should follow standardized medication regimens in relation to meals (levodopa at least 30 minutes before or 60 minutes after a meal). Certain medications can alter levodopa absorption (13) (Table 2).

Table 2. Factors influencing the pharmacokinetics of levodopa plus decarboxylase inhibitor (according to 8–12, 14–16, 19, e40–42).

Factor	Cmax	tmax	AUC	t1/2
Nutrition (fat and large neutral amino acids)	↓	↑	↓	↔
Advanced age	↑	↔	↑	↑
Sex (women vs. men)	↔	↔	↑	↔
Low body weight	↑	n. e.	↑	n. e.
Delayed gastric emptying	↔ ↓	↑	↓	n. e.
COMT inhibitor	↑ ↔	↔	↑	↑
Compared with standard tablet
Extended-release preparation	↓	↑	↓	↑
Soluble tablet	↑ ↔	↓	↔	↔
Inhalation	↓	↓	↓	↔

The levodopa AUC after a standard dose is higher in older patients than in young patients (19, e40). A low body weight is associated with high peak concentrations of levodopa and a high area under the concentration-time curve (AUC) (e41). In comparison with men, women have an increased levodopa AUC in plasma, even after correcting for body weight (e42).

↑ increased; ↔ constant; ↓ decreased: if more than one arrow is listed, then the literature references are inconsistent

AUC, area under the concentration-time curve;

C_max, peak plasma concentration;

COMT, catechol-O-methyltransferase; n. e., not examined;

t_max, time to maximum plasma concentration;

t_1/2, elimination half-life

Tablets designed to dissolve, whether suspended or undissolved, result in faster absorption of levodopa and decarboxylase inhibitor as compared with conventional tablets and capsules. Extended-release preparations of levodopa plus a decarboxylase inhibitor result in a slower rise of levodopa levels and a delayed fall in serum concentration (14). Extended-release levodopa preparations are not recommended for daytime use due to their lower and more variable bioavailability. But daytime administration of extended-release levodopa in patients with uncontrolled motor fluctuations or dyskinesia may be suitable for extending the periods of good mobility in the absence of dyskinesia (e6, e7).

Inhaled levodopa shortens the time between ingestion and reaching peak levels as compared with oral levodopa (15, 16). The inhalation powder contains only levodopa. It is only used for akinetic periods in patients being treated simultaneously with levodopa and a decarboxylase inhibitor. Any advantage over soluble levodopa for older patients is still uncertain. There is a considerable need for the training of older patients in the correct handling of inhalers (17).

Pharmacodynamics

In the early stages of Parkinson’s disease, fluctuations in the action of levodopa are minimal, despite large variations of plasma concentrations. After a treatment period with levodopa of around five years, fluctuations in its effect develop which are related to fluctuations in plasma levels (8, 9, 18). With a long-term disease course, levodopa plasma concentrations must therefore be kept as constant as possible at times when the patient is awake.

Dose finding

The amount of each single dose and dose intervals are titrated to individual patient needs (8). In the early stage of the disease, a three-times-daily dosing schedule is often chosen. The dose interval can be shortened and/or levodopa elimination slowed down in patients with advanced Parkinson’s disease (11). As the disease progresses, the minimum plasma concentration of levodopa required to improve mobility increases, thus requiring sufficiently high individual doses. (19).

In severely affected patients, the first morning dose and any interim medication taken as needed during off-phases are administered as a soluble tablet taken in dissolved form. (20, 21). Patients with an advanced stage of the disease are given an extended-release preparation for the night (22). Some of these patients require a further dose of levodopa during the night (2–4 o’clock).

Treatment options for motor complications

Catechol-O-methyltransferase inhibitors

Catechol-O-methyltransferase (COMT) inhibitors are used in combination with levodopa to prolong the effects of levodopa. The usual COMT inhibitors entacapone and opicapone hardly penetrate the central nervous system (CNS) (23). They scarcely cause any CNS side effects beyond those associated with elevated plasma levels of levodopa. This allows their use in older patients with Parkinson’s disease (Table 1 and 3). The most common side effect is dyskinesia secondary to elevated plasma levels of levodopa (24).

Entacapone is administered together with levodopa because of its short half-life of around 2.5 hours. Combination preparations with levodopa (+ decarboxylase inhibitor) simplify treatment. Entacapone causes the urine to turn a reddish color which can alarm some patients (25, e8). Opicapone also has a short half-life. The opicapone-COMT complex remains stable for a long time, so that COMT activity still presents a decrease of approximately 65% after 24 hours (25, e9). Opicapone 50 mg is therefore taken once daily at least one hour before or after levodopa before going to sleep. Tolcapone can cause rare liver damage (25) and should be avoided in older patients (e10).

Dopamine-antagonists and monoamine oxidase inhibitors

Both substance classes have an unfavorable effect/side effect ratio in the majority of older patients (6) (Figure). Common side effects of both substance classes are listed in Table 1.

In an open randomized study comparing dopamine agonists with MAO-B or COMT inhibitors in patients inadequately controlled on levodopa, patient-rated quality of life was better with a MAO-B inhibitor as adjuvant therapy than with COMT inhibitors (e11). The treatment discontinuation rate was lowest for COMT inhibitors.

Amantadine, MAO-B inhibitors (selegiline, rasagiline, and especially safinamide) (e12), and dopamine agonists (pramipexole, ropinirole, piribedil, and rotigotine) are usually not recommended for older patients, mainly because of the risk of developing psychosis and orthostatic dysregulation. Rotigotine is administered via a transdermal patch, may be immediately removed should side effects develop, and appears to be better tolerated than other dopamine agonists (e13). However, rotigotine is also only recommended to a limited extent especially for palliative purposes at the end of life (e14, e15). The scale of side effects from dopamine agonists and MAO-B inhibitors in patients over 80 has not been sufficiently assessed (e16).

Levodopa therapy via a nasogastric tube, percutaneous gastroenterostomy, and percutaneous jejunal tube

Intravenous levodopa medications are not available for routine clinical use (e17). Patients with Parkinson’s disease who (occasionally) cannot swallow receive their medication via a nasogastric or percutaneous nasogastric tube (see [2] for more information about the possibility of administering various preparations via enteral tubes). A nasogastric tube can be lifesaving when Parkinson’s symptoms deteriorate, for example, as a result of an infection (26). Percutaneous tubes are usually tolerated in the long-term if they are correctly secured.

Should unpredictable fluctuations in levodopa plasma concentrations develop, then the jejunal administration of levodopa plus a decarboxylase inhibitor via an infusion pump can ensure constant levodopa plasma concentrations (27) (eFigure). Pump therapy can also be used in patients with dementia. Entacapone is also suitable for continuous jejunal infusion together with levodopa/carbidopa (e18). It reduces the required infusion volume (28).

eFigure.

Plasma concentrations of levodopa and carbidopa (27) (licensed under CC BY-NC) (Othman AA et al., 2015) (mean value ± standard deviations) after oral administration of levodopa–carbidopa tablets (10 : 1 levodopa/carbidopa ratio; a, c) and intrajejunal infusion of levodopa–carbidopa intestinal gel (4 : 1 levodopa/carbidopa ratio after insertion of a PEJ tube; b, d) in Japanese patients with advanced Parkinson’s disease (n = 5). LCIG = levodopa-carbidopa intestinal gel

In a long-term observational study involving 324 patients (duration 54 weeks, patient age 64.1 ± 9.1 years, disease duration 12.5 ± 5.5 years, median jejunal levodopa daily dose 1547 mg; 272 completed the trial), the most common side effects were complications associated with insertion of the jejunal tube. They mainly occurred shortly after insertion of the tube (34.9%). The daily off-time decreased by a mean of 4.4 h/65.6%, on-time without troublesome dyskinesia increased by 4.8 h/62.9%, the on-time with troublesome dyskinesia decreased by 0.4 h/22.5 % (e44).

The advantages of levodopa administration via a jejunal tube in older patients are good symptom control and avoidance of levodopa peak levels. Pump treatment avoids the need for multiple single drug doses. Nursing staff can irrigate the pump and switch it on in the morning and switch it off in the evening. If necessary, the pump can continue to run during the night at a low dose. There is also the option of bolus administration as needed. Possible complications include dislocation or obstruction of the tube and inflammation around the insertion site. Patients with dementia and severe fine motor impairments are unable to operate the pump. Continuous levodopa administration is therefore reserved for patients who can operate the system themselves or who are very well cared for by relatives and/or nursing staff (e21).

Subcutaneous pump systems

Foslevodopa/foscarbidopa (ratio of 20:1) has been available since 2023 for continuous subcutaneous application. Its administration is similar to that of an apomorphine pump which should not be used in older patients due to potential psychiatric side effects (29, e19). Complications primarily include erythema, nodules, and edema or infection at the puncture site. Since subcutaneous infusion is not invasive, the importance of this form of treatment in older patients will most likely increase (e20).

Deep brain stimulation

The indication for deep brain stimulation (DBS) include side effects and variations of efficacy of dopaminergic therapy (e21). Because cognitive deficits can significantly deteriorate, and personality changes (for example, depressions) can develop postoperatively (e22), this method should only be considered for older patients in exceptional cases (e23).

Unsuitable drugs

Not only high-potency classical neuroleptics, but also drugs usually classified as atypical neuroleptics (with risperidone as the lead compound), as well as low-potency sedating and sleep-inducing neuroleptics (lead compounds melperone, pipamperone, prothipendyl), metoclopramide, and in rare case other medications, for example flunarizine, lithium, valproate can exacerbate Parkinson’s symptoms or cause drug-induced parkinsonism (e24). The use of antipsychotics increase mortality in patients with Parkinson’s disease. In a retrospective case-control study involving 7877 matched pairs of patients (age 76.3 ± 7.7 years, mean age ± standard deviation, 99.2% men) this risk was higher for haloperidol (hazard ratio 4.8), risperidone (2.6), and olanzapine (2.8) than for quetiapine (1.9), while there was not sufficient data available for clozapine (30). All other measures must be fully exhausted before using neuroleptics in patients with Parkinson’s disease (Table 3, Box 1).

Box 1. Treatment of hallucinations brought on by Parkinson’s disease (6–8, 31–35).

• Exclude or treat infections

• Exclude or treat toxic-metabolic causes (in particular anticholinergics, drugs with anticholinergic side effects, renal failure, hyponatremia or hypernatremia, hypercalcemia)

• Restore physiological sleep-wake rhythm

• Discontinue non-essential non-Parkinson’s medication (antidepressants, benzodiazepines, and opioids)

• Reduce or discontinue anti-Parkinson’s drugs with an unfavorable effect/side effect ratio (amantadine, dopamine agonists, MAO-B inhibitors, possibly COMT inhibitors)

• Reduce levodopa dose

• Antipsychotic medication

• For Parkinson’s disease dementia: treatment with rivastigmine

Treatment options for other complications

Parkinson’s disease psychosis

Older patients with Parkinson’s disease have a high risk (30–40%) of developing psychosis (Table 3, Box 1) (31). Mild cognitive impairment or dementia, advanced age, duration and severity of the Parkinson’s disease, loss of sight or hearing, as well as psychiatric and medical comorbidities increase this risk (30). The occurrence of hallucinations, even when initially mild and with preserved insight, may indicate initial psychotic development. With hallucinations or delusions, treatment should preferably be limited to levodopa (if necessary, in combination with a COMT inhibitor) (Figure).

Clozapine is the only approved antipsychotic whose effect without worsening of motor function has been demonstrated in randomized trials (32–34). White blood count and neutrophilic granulocytes must be checked on a weekly basis due to the risk of developing agranulocytosis. Quetiapine also does not worsen motor function but was not reliably effective in randomized trials (30, e25, e26). It is often used “off label” for Parkinson’s disease.

Akinetic crisis

Possible causes such as dehydration or infection should be treated first. Levodopa is administered via a nasogastric tube. The precondition is preserved gastrointestinal motility (auscultation of the abdomen, adequate transport of administered fluids via the nasogastric tube, sufficient defecation frequency). A case study has shown the effectiveness of foslevodopa as a subcutaneous infusion for akinetic crisis in the absence of a nasogastric tube (e27).

The glutamate antagonist amantadine is available in intravenous form and can improve motor function in an emergency secondary to akinetic crisis. It accumulates rapidly if renal function is impaired (e28). Its use requires comprehensive monitoring in older patients.

Parkinson’s disease dementia

Cholinergic antidementia drugs are effective for dementia associated with Parkinson’s disease (7, 35). Of the cholinergic anti-dementia drugs, only rivastigmine as a hard capsule is approved for Parkinson’s disease dementia. The somewhat better-tolerated rivastigmine patch is an off-label use in Parkinson’s disease dementia (7, 35). Although rivastigmine was associated with nausea, vomiting, diarrhea, and increased tremor, it did reduce the incidence of hallucinations and orthostatic dysregulation in patients with Parkinson’s disease (35). Another point in favor of cholinergics is their life-prolonging effect, which is somewhat more pronounced in patients with Parkinson’s disease than in those with Alzheimer’s (risk ratio 0.56 and 0.64 in comparison with no cholinergic drug) (36).

Cholinesterase inhibitors reduce the incidence of falls in patients with Parkinson’s disease by around 50% (37). This was also true in a randomized trial for patients without dementia (38) (Table 3).

In a small randomized trial, memantine (not approved in Germany either for Parkinson’s disease dementia or for Parkinson’s disease) improved postural instability but not gait (e29). In Parkinson’s disease dementia and dementia with Lewy bodies, it shortened reaction time to visual yes/no stimuli by an average of 130 ms and improved performance in the immediate and delayed word recognition test by an average of 3% and 5%, respectively, (e30).

Continence impairment

A number of anticholinergics for reducing detrusor activity within the bladder have adverse CNS effects. Trospium is a urinary antispasmodic drug with the least CNS penetration and the fewest cognitive side effects due to its hydrophilic properties (39). Anticholinergics with relatively specific action on muscarinergic M3 receptors are also supposed to cause minor CNS side effects (e31).

Treatment for autonomic nervous system disorders

Reduced bowel motility associated with constipation and orthostatic hypotension are caused by the underlying disease and pharmacologic therapy. Constipation is treated as long as possible with a high-fiber diet and adequate fluid intake, movement exercises, physiotherapy, and osmotic laxatives (for example, macrogol) or/and probiotics (40). Rivastigmine has a prokinetic effect on the gastrointestinal tract (35).

Orthostatic dysregulation (Box 2) is treated with lower limb compression therapy (e32). Leg muscle training, for example, running on the spot, cycling as well as cold showers and alternating baths, help tone the leg vessels and reduce the degree of orthostatic dysregulation (e33). All antiparkinson drugs, especially dopamine agonists, and clozapine can worsen orthostatic hypotension (e34).

Box 2. Treatment of symptomatic orthostatic dysregulation in Parkinson’s disease (40, e32–e38).

• Avoid dopamine agonists

• Moderate increase of fluid and salt intake (beware of heart failure)

• Stand up slowly

• Avoid heavy physical exertion

• Correct any existing anemia

• Avoid large meals and alcohol

• Reduce venous pooling using physical measures

  • support stockings, support tights, abdominal compression*

  • train leg muscles

  • cold stimuli to the lower limbs (contrast baths).

• Activate the renin–angiotensin–aldosterone system

  • sleep with upper body elevated

  • fludrocortisone 1–3 times 0.1 mg/d; not to be used in patients with heart failure; according to product information, contraindicated in patients >65 years!

• Sympathomimetics

  • droxidopa 3 times 100–600 mg/d (only available in Germany through international pharmacies)

  • midodrine twice 2.5 mg/d

  • etilefrine 3 times 10 mg/d

* Compression tights are most effective; knee-length compression stockings are usually not sufficiently effective. Thigh-high compression stockings are prescribed as a compromise in the event that problems arise with putting on and taking off tights. Abdominal compression binders are also effective.

Apart from promoting intestinal motility, antidopaminergic drugs also have a positive effect on orthostatic dysregulation. Metoclopramide is contraindicated in Parkinson’s disease due to its blockade of dopamine receptors in the central nervous system. In a British cohort study involving 5114 patients with Parkinson’s disease (mean age 74.5 years, total mortality 7.4%/year), the use of domperidone, which hardly crosses the blood-brain barrier, was associated with a doubling of total mortality (e35).

Sympathomimetic drugs, for example, midodrine, etilefrine, can be administered short-term to raise blood pressure and treat orthostatic dysregulation, yet with limited success (40, e36, e37).

Droxidopa, an oral norepinephrine precursor (only available in Germany through international pharmacies), improves orthostatic dysregulation at a dose of 100 to 600 mg, three times daily, in various neurodegenerative diseases, including Parkinson’s (40, e38).

The effect of mineralocorticoids is to increase blood pooling. They cannot be used in the majority of older patients due to potential concomitant heart failure.

Summary

In older patients with Parkinson’s disease, treatment regimens are often too complex and so produce avoidable side effects without providing any real benefit to the patients. Studies on the effect of antiparkinson therapy in patients aged 80 and older are very rare. Simplifying the treatment by changing to levodopa plus a decarboxylase inhibitor, possibly in combination with a COMT inhibitor and the cholinergic drug rivastigmine, can improve motor, cognitive, and autonomic symptoms in the later stages. Therapeutic nihilism is also inappropriate for severely ill older patients with Parkinson’s disease. Improvement in the quality of life can be achieved by the intervention of specialists in the treatment of Parkinson’s disease (e39). Non-pharmacological therapy (eSupplement) is just as important as pharmacotherapy in preventing admission to a nursing home and confinement in bed.

eSupplement. Non-pharmacological management of Parkinson’s disease in the elderly.

The German consensus-based S2k Guideline “Parkinson’s disease” recommends enabling patients with Parkinson’s disease access to therapeutic approaches aimed at patient activation and engagement (physiotherapy, occupational therapy, and art therapy) (7). The benefit of these forms of treatment has been proven for this group of patients. Data relating specifically to geriatric patients with Parkinson’s disease are not available, but numerous studies included a large proportion of older patients. Due to their immobility or cognitive impairment, providing regular therapy for older patients is challenging, especially when resources are limited, while participation in group therapy sessions is often only possible to a limited extent (1).

Physiotherapy is a decisive pillar in the treatment of Parkinson’s disease. Evidence is available on the efficacy of exercising high-amplitude movements (based on the LSVT-BIG program) as compared with training in Nordic walking or domestic non-supervised exercises (e45). A Cochrane analysis identified 39 studies involving 1827 participants. Physiotherapy improved walking speed and activities of daily living in comparison with untreated control patients. Indirect comparisons between different physiotherapeutic methods in the above-mentioned meta-analysis did not reveal any evidence for the superiority of any specific procedure (e45, e46). In a three-armed randomized trial lasting six years, an initial three-week, high-intensity sensorimotor exercise program with no follow-up training improved Parkinson’s symptoms for up to a year, but initial high-intensity training plus a subsequent six-year maintenance program was required to maintain or increase the initial improvements and to improve quality of life (e47).

In a three-armed eight-week randomized trial involving older patients (60 years and older), functional training, bicycle exercise, and use of computer games which require physical movement from the player (exergaming) improved walking capacity (six-minute walk) and the ability to stand up from a sitting position. There were no significant differences between the three groups, so all three approaches appeared to be more or less equal (e48). Physiotherapeutic training programs reduced the frequency of falls by 26% and the number of fallers by 10%. However, it is not certain whether this is also reflected by a reduced frequency of fractures (37). A synopsis of appropriate forms of treatment may be found in the “European Physiotherapy Guideline for Parkinson’s Disease” (e49).

In a small randomized trial (age of the intervention group 68 ± 7 years), a multimodal exercise program (three one-hour sessions per week for six months) reduced sleep disturbances and improved activities of daily living (measured using the Pfeffer Instrumental Activities Questionnaire) (e50).

A six-month randomized trial, in which the intervention group received an individually tailored, home-based training program with balance and strengthening exercises, was negative with respect to the primary endpoint of fall prevention. The patients documented their falls in falls diaries. Balance and functional strength as secondary endpoints were improved by the intervention, and there were fewer near-falls. Patients with moderate disease appeared to benefit from the intervention, while frequency of falls rose in those most severely affected, especially patients with freezing of gait (e51, e52).

A randomized trial involving patients with mild to moderate Parkinson’s disease and a mean age of around 70 years compared home physical therapy with a telerehabilitation program: Both interventions mitigated motor symptoms of the disease and improved quality of life. Home physical therapy was more effective in older patients, and compliance was higher with home physical therapy than with telerehabilitation (e53).

In a meta-analysis of seven randomized clinical and four quasi-experimental studies (n = 548, average age 68 years, 50% women), Parkinson’s patients who undertook tai chi had better balance and improvement of one or more aspects of well-being (e54). In a meta-analysis of 14 small randomized trials (n = 524, average age 60–76 years, duration 4–12 weeks), virtual reality-based rehabilitation resulted in improvement of balance, but not gait ability, activities of daily living, and quality of life in comparison with conventional physical therapy (e55).

Another meta-analysis of ten trials examining the effect of whole-body vibratory stimulation therapy showed an improvement of gait by this form of treatment (e56). It should be noted that very frail or anxious people often do not tolerate this therapy method.

A COCHRANE meta-analysis which appeared in 2024 of 154 randomized controlled trials involving 7837 patients with mostly mild to moderate disease and no major cognitive impairment (average age 60–74 years) revealed benefit of the majority of types of physical exercise as compared with a control group with no physical exercise. Dance therapy as well as gait and balance training only moderately improved motor symptoms. Multimodal training had a minor positive effect on motor skills. Aqua-based training programs in particular had a positive effect on quality of life. The complications most commonly reported were falls and aggravation of pain (e57). Occupational therapy can also contribute much towards improving activities of daily living and specific motor problems in patients with Parkinson’s disease. Here too, efforts are being made to compile evidence-based therapeutic approaches (e58).

In three randomized trials involving 63 participants, speech and language therapy produced an increase in speech volume by an average of 5 to 11 dB, an effect of probable clinical significance. Although this effect was reduced over the further course, it was still evident after six months (e59). Similar to the LVST-BIG program, LSVT speech training is also recommended for patients with Parkinson’s disease.

Dysphagia can result in life-limiting aspiration pneumonia in advanced stages of Parkinson’s disease. Patients with dysphagia should use the opportunity given by phases of best mobility to eat their food. Swallowing therapy uses compensatory and rehabilitative strategies. Based on randomized studies, there is low-level evidence suggesting the effectiveness of speech therapy for swallowing disorders in patients with Parkinson’s disease. (e60).

A meta-analysis including 58 articles looking at various forms of music therapy (listening to music, rhythmic auditory stimulation, singing alone or in groups) showed improvements both in motor (especially increase in stride length, less difficulty initiating movement) and non-motor areas (social, emotional, cognitive) (e61).

Cognitive training may induce only minor improvements, for example, in attention or verbal memory. An effect on activities of daily living and quality of life was not demonstrated (e62). Computer-based cognitive training revealed statistically significant improvements, especially in patients with mild cognitive dysfunction (e63).

In a randomized trial (mean age 71 versus 70 years, predominantly men) involving patients with Parkinson’s disease with four or more incontinence episodes per week, behavioral therapy (bladder training, autonomous fluid management, pelvic floor muscle exercises) did not result in a reduction in incontinence as compared with the control group, but it did improve quality of life and reduce concerns about incontinence (e64).

Small randomized trials reported a favorable effect of transcranial magnetic stimulation on musculoskeletal pain (e65) and motor function (e66). Many anxious and/or cognitively impaired patients are not suitable for this form of therapy.

A meta-analysis of five randomized controlled trials with a total of 173 patients (e67) showed that bright light therapy improved depressive symptoms and sleep disturbances in patients with Parkinson’s disease.

Nurse care managers: A complex randomized intervention study with specialized nursing staff who communicated with medical Parkinson’s disease specialists using standardized telephone contacts and electronic means improved several care quality indicators of Parkinson’s disease in US army veterans with Parkinson’s disease and an average age of 71 years. The authors concluded that the interventions must be further refined to improve patient-centered outcomes (e68).

We are not aware of any randomized studies on the effectiveness of early rehabilitative complex treatment as practiced in Germany in older patients with Parkinson’s disease. A meta-analysis of eight observational studies (1022 patients, average age 64 to 75 years, of which 25 suffered from atypical Parkinson’s syndrome) demonstrated positive effects on motor and non-motor symptoms, activities of daily living, and quality of life (e69).

Questions relating to the article in issue 15/2025:

The Treatment of Older Patients with Parkinson’s Disease

The closing date for entries is 24 July, 2026. Only one answer is possible for each question.

Please select the most appropriate answer.

Question No. 1

How many people in Germany suffer from Parkinson’s disease?

1. around 61 000

2. around 95 000

3. around 150 000

4. around 220 000

5. around 310 000

Question No. 2

What percentage of patients suffering from Parkinson’s disease go on to develop dementia in the course of the disease?

1. around 25%

2. around 40%

3. around 50%

4. around 80%

5. around 95%

Question No. 3

Which reason is provided in the article why treatment of younger patients with Parkinson’s disease is often not initiated with levodopa?

1. Because dyskinesia may develop after about five years of treatment with levodopa.

2. Because levodopa is not effective enough against the symptoms of Parkinson’s disease.

3. Because levodopa is more effective in older patients.

4. Because the effect of levodopa rapidly decreases after about two years.

5. Because levodopa can slowly lead to blindness.

Question No. 4

Which statement regarding the administration of levodopa is not appropriate?

1. Levodopa is usually taken in oral form.

2. Levodopa may also be taken by inhalation.

3. Levodopa is commonly administered intravenously.

4. Levodopa is commonly taken as a sustained-release preparation for the night.

5. Levodopa is usually taken in combination with a decarboxylase inhibitor.

Question No. 5

Which Parkinson’s medication may cause the urine to turn a reddish color?

1. carbidopa

2. entacapone

3. levodopa

4. opicapone

5. foscarbidopa

Question No. 6

What do the drugs carbidopa, entacapone, and benserazide have in common?

1. They reduce the half-life of L-dopa in the organism.

2. They reduce the effect of L-dopa in order to offset peaks.

3. They inhibit the metabolism of L-dopa outside the central nervous system.

4. They have a similar effect to L-dopa, only slower, thus covering a longer period of time.

5. They accelerate the metabolism of L-dopa to dopamine, so patients benefit from the administration of L-dopa more rapidly.

Question No. 7

Which of the following dopamine agonists is applied as a transdermal patch?

1. rotigotine

2. ropinirole

3. piribedil

4. apomorphine

5. pramipexole

Question No. 8

Which statement regarding the administration of foslevodopa/foscarbidopa is most appropriate?

1. Foslevodopa/foscarbidopa has been approved since 2020 for continuous intravenous application at a ratio of 1:5.

2. It has been possible to administer foslevodopa/foscarbidopa intrathecally at a ratio of 1:20 since 2025.

3. Foslevodopa/foscarbidopa may be administered via a nasogastric tube at a ratio of 1:10.

4. It has been possible to give foslevodopa/foscarbidopa by continuous subcutaneous administration at a ratio of 20:1 since 2023.

5. It has been possible to administer foslevodopa/foscarbidopa intrathecally at a ratio of 1:1 since 2025.

Question No. 9

According to the information in the article, which drugs should preferably not be used in patients suffering from Parkinson’s disease due to possible severe side effects or otherwise only if all other measures have been exhausted?

1. neuroleptics

2. antihypertensives

3. non-steroidal antirheumatics

4. diuretics

5. corticosteroids

Question No. 10

Which statement regarding orthostatic dysregulation in Parkinson’s disease is not appropriate?

1. Orthostatic dysregulation may be treated by lower limb compression therapy.

2. All therapeutic agents used to treat Parkinson’s disease can exacerbate orthostatic hypotension.

3. Metoclopramide is suitable for treating orthostatic hypotension in Parkinson’s disease due to its good penetration through the blood-brain barrier.

4. Sympathomimetics (such as midodrine and etilefrine) may be used in patients with Parkinson’s disease to temporarily raise blood pressure.

5. In a British study involving patients with Parkinson’s disease, the administration of domperidone was associated with a higher total mortality.