Editorial Opinion

New and Appropriate Goals for Parkinson Disease

Physical Therapy
J. Eric Ahlskog, PhD, MD

Physical and occupational therapy have long been components of Parkinson disease (PD) treatment. Prior to the advent of levodopa, this was a primary therapeutic modality.
What is the current role for physical therapy in PD? Should everyone with PD be referred? Is it cost-effective? What should
be the therapeutic goals and program content?
In the United Kingdom, cost-effectiveness is an especially
relevant consideration in the context of its single-payer National
Health Service. The cost-effectiveness of routine referral of patients with earlier-stage PD for physiotherapy and occupational
therapy was addressed in an
article in this edition of JAMA
Neurology.1 Half of more than
Related article page 291
700 patients with PD from
across the United Kingdom were randomized to standard practice physiotherapy and occupational therapy (median, 4; hourlong therapy sessions). Compared with the control group, this
therapy intervention failed to meaningfully influence the activities of daily living or quality-of-life measures, with follow-up at
3 and up to 15 months. The investigators concluded that, This
evidence does not support the use of low-dose, patient-centered,
goal-directed physiotherapy and occupational therapy in patients
in the early stages of PD.1 The authors cited prior studies that
tended to support this conclusion.
These results should be interpreted with attention to the
study details. Patients in this investigation had mild to moderate PD and the enrollment criteria excluded patients whose
clinicians believed needed physical/occupational therapy.
Thus, one may conclude from this investigation that blanket
referrals of all patients with earlier-stage PD for routine physical or occupation therapy appears to be cost-ineffective.
Intuitively, certain PD-related symptoms should benefit from
routine physical therapy strategies, including problems such as
gait freezing, imbalance/fall risk, or immobilized limbs. Patients
with PD with shortened stride or reduced arm swing benefit from
strategies for consciously increasing attenuated movements. Such
circumscribed problems were not the focus of this investigation.
The therapy schemes performed in this investigation are
also notable: Physiotherapy and [occupational therapy] were
deliveredby qualified therapists working within the National Health Service (NHS) per local practice. Such routine
physical therapy practices are universally established and have
been used for decades in treating PD. Per convention, these primarily focus on stretching, balance, posture, gait, and strategies for facilitating activities of daily living. More recently, protocols for enhancing movement amplitudes have been added
(eg, consciously focusing on increasing stride length and arm
movements). However, these conventional physical therapy
practices take no advantage of what has now become increasingly apparent: ongoing aerobic exercise may slow the progression of PD.2 To date, it has not been part of physical therapists job description to facilitate ongoing aerobic exercise.
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The progression of PD extends far beyond dopaminergic

substrates and includes potential for levodopa-refractory dementia, dysautonomia, and medication-unresponsive motor
symptoms. No medications are proven to slow such PD progression. However, there is substantial, albeit indirect, evidence for regular vigorous exercise and aerobic fitness possibly providing a neuroprotective effect. This comes from a
variety of investigations, which may be summarized as
follows.2 Animal studies have documented exercise-related increases of brain neurotrophic factors, synaptic proteins, neuroplasticity factors, hippocampal neurogenesis, hippocampal long-term potentiation, recovery from neurotoxins, and
enhanced memory. Habitually exercising humans have evidence of significantly larger brain cognitive regions, better cortical connectivity (functional magnetic resonance imaging),
better cognitive scores, and reduced later frequencies of PD,
dementia, and mild cognitive impairment.
This exercise literature2 poses the question of whether national health care administrations should endorse and financially
underwrite aerobic exercise programs for all with PD. This would
entail far more than single therapy sessions. Our culture tends
to reinforce a sedentary lifestyle, and new exercise habits would
need to be periodically monitored and reinforced. Such a PD
exercise program would necessarily begin with optimized
carbidopa/levodopa treatment, which is often necessary to
allow exercise.3 The envisioned therapy program would begin
with individualized selection of aerobic exercise routines that
would be tolerated and maintained by each person with PD. There
is no one-size-fits-all program for exercise and all aerobic exercise options should be on the table. Such a program would necessarily start modestly for some but with therapist-guided advances and, sometimes, with tough love.
A challenge for those endorsing such a structured aerobic exercise protocol is proof of benefit. A randomized clinical trial
among patients with PD is going to be highly susceptible to confounding factors. Many in our culture are disinclined to exercise
even in the absence of neurologic disease; maintaining persistent adequate levels of aerobic exercise will be a challenge in such
people. Such a program would require people to also exercise on
their own, where bad exercise habits can flourish. On the other
hand, motivated patients with PD randomized to the control
group may recognize potential exercise benefits and engage on
their own. Moreover, such a controlled study of PD progression
would necessarily require prolonged follow-up (eg, a few years),
and the expected dropout rate would compromise interpretation.
Realistically, perhaps the best we can do is base our PD exercise
recommendations on the existing published literature.
To summarize, first, current physical/occupation therapy
referrals for those with PD should be for specific problems that
are likely to benefit. Second, physical therapy practices should
begin to incorporate facilitation of ongoing aerobic exercise and
fitness.
(Reprinted) JAMA Neurology March 2016 Volume 73, Number 3

Copyright 2016 American Medical Association. All rights reserved.

269

Opinion Editorial

ARTICLE INFORMATION

Conflict of Interest Disclosures: None reported.

Author Affiliation: Department of Neurology,

Mayo Clinic, Rochester, Minnesota.

REFERENCES

Corresponding Author: J. Eric Ahlskog, PhD, MD,

Mayo Clinic, Department of Neurology, Gonda 8,
Rochester, MN 55905 (eahlskog@mayo.edu).
Published Online: January 19, 2016.
doi:10.1001/jamaneurol.2015.4449.

1. Clarke CE, Patel S, Ives N, et al. Physiotherapy

and occupational therapy vs no therapy in mild to
moderate Parkinson disease: a randomized clinical
trial [published online January 19, 2016]. JAMA
Neurol. doi:10.1001/jamaneurol.2015.4452.

2. Ahlskog JE. Does vigorous exercise have a

neuroprotective effect in Parkinson disease?
Neurology. 2011;77(3):288-294.
3. Ahlskog JE. Cheaper, simpler, and better: tips for
treating seniors with Parkinson disease. Mayo Clin
Proc. 2011;86(12):1211-1216.

Implementing Recommendations
for Depression Screening of Adults
How Can Neurology Contribute to the Dialogue?
Helen S. Mayberg, MD

The US Preventive Services Task Force (USPSTF) has offered its

updated recommendations for the screening for depression in
adults. The document, published this week in JAMA,1 updates
a 2009 review of the evidence as to the net benefit of accurate
diagnosis, effective treatment,
and appropriate follow-up after depression screening for
Related article at jama.com
adults older than 18 years,
including pregnant and postpartum women, complementing
previous recommendations for depression screening in children
and adolescents (http://www.uspreventiveservicetaskforce
.org). There is no question that primary care screening offers a
first-line medical opportunity to identify patients with an
undiagnosed major depressive episode. Use of standardized
screening instruments and evidence-based treatments are a
critical first step. That said, an unsettling reality remains: how,
even with improved efficiency of screening and more timely
diagnoses, do we secure the necessary resources to ensure that
depressed patients not only receive treatment and follow-up,
but that the treatment selected is both appropriate and
optimized for the individual. Compounding these challenges,
neurological patients with depression, even when identified,
may be reticent to accept psychiatric treatment,2 and like internal
medicine and primary care, the time and resources needed to
address the behavioral symptoms are often eclipsed by core
demands of the principal neurological or medical condition.
For a patient presenting with major depressive episode, an
antidepressant medication or evidence-based psychotherapy is currently recommended as first-line treatment, with
remission rates to these 2 options roughly equivalent in all patients except the most severely ill.3 With this perceived equivalency, treatment selection is often based on factors such as patient and health care professional preference, cost and
accessibility, and potential adverse effects. However, the odds
are actually against remission in patients currently treated
using this approach. At best, 40% of patients achieve remission with a first treatment, and the wrong first choice has
significant individual and societal costs due to continued dis270

tress, risk of suicide, loss of productivity, and wasted resources associated with 2 to 3 months of an ineffective treatment. Moreover, among the roughly 60% to 70% of depressed
patients who do not remit with their first treatment, many do
not return to explore other options, with potential lethal
consequences.4 These same concerns hold for depression presenting in patients with neurological diseases and other medical illnesses where the combined presence of a mood disorder has a magnified effect on disability.5
Clearly, treatments are highly effective in some individuals, but there is no reliable way to match patients to their best
treatment option or to avoid those that are unlikely to be effective, even in the setting of equal access. Developing reliable biomarkers that can stratify individual patients to specific treatments is essential to achieve the goal of a more
personalized level of care for patients with depression and all
neuropsychiatric disorders.6 Many medical specialties such as
those treating heart disease and cancer now routinely use patient-level biological measures to subtype and stratify patients to treatments, and to guide treatment modifications with
disease progression or categories of disease risk, substantially improving patient outcomes.
Toward a precision medicine approach for depression, various strategies have been tested, including clinical,
imaging, genetic, electroencephalographic, and immunological metrics, but with limited clinical impact thus far.
Motivated to translate ongoing advances in functional and
structural neuroimaging methods and mounting evidence
of (1) distinct patterns of brain dysfunction across clinically
defined depression subgroups, (2) regional correlates of specific mood, motor, and cognitive syndrome dimensions, and
(3) differential change patterns with mechanistically distinct treatments,7 investigations of brain-based biomarkers
that predict treatment outcomes to standard first-line treatments have been initiated. Recent studies have identified
some initial promising imaging biomarker candidates that
predict remission and nonresponse to cognitive behavioral
therapy or a standard selective serotonin reuptake inhibitor

JAMA Neurology March 2016 Volume 73, Number 3 (Reprinted)

Copyright 2016 American Medical Association. All rights reserved.

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