Depression May Aggravate Motor, Cognitive Symptoms in Newly Diagnosed Parkinson’s Patients, Study Reports

Depression in newly diagnosed Parkinson’s patients is associated with initial motor deficits and worse cognitive function, unrelated to dopamine loss, a study suggests.

These patients also require higher doses of medications at follow-up.

The study, “The presence of depression in de novo Parkinson’s disease reflects poor motor compensation,” was published in the journal PLOS ONE.

Early burden of non-motor symptoms, such as depression, is considered a relevant prognostic marker indicative of poor motor outcomes in Parkinson’s disease. Because motor symptoms only appear after marked degeneration of dopamine-producing neurons, scientists believe that significant motor system compensation occurs in these patients, providing a way to overcome dopamine loss.

Patients with de novo Parkinson’s — newly diagnosed and still untreated — with either olfactory dysfunction (loss of sense of smell) or rapid eye movement sleep behavior disorder have greater motor deficits than those without these symptoms, but they both have the same levels of dopamine, suggesting that the early presence of non-motor symptoms correlates with less compensatory ability.

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The early occurrence of depression in de novo Parkinson’s indicates widespread involvement of pathological lesions, which may limit motor compensatory ability and lead to greater physical impairment. However, the link between depression and dopamine depletion in early Parkinson’s is still unclear.

Aiming to address this gap and to explore whether early occurrence of depression is associated with reduced motor compensation, researchers from Yonsei University College of Medicine in South Korea analyzed 474 patients, at a mean age of 64.6 years, including 242 men, with de novo Parkinson’s without dementia. The mean duration of their symptoms was 18.3 months.

The patients underwent positron emission tomography (PET) scans for the dopamine transporter (DAT) — responsible for the uptake of dopamine into neurons from the synapse, where neurons communicate — in the striatum, a key brain region involved in movement and cognition.

Depression was assessed using the Beck Depression Inventory, a 21-question multiple-choice self-report inventory composed of items related to symptoms of depression. Motor symptom severity was evaluated with Part III of the Unified Parkinson’s Disease Rating Scale, and the Mini-Mental State Examination was used to measure cognitive function.

Depression scores were divided into three levels: 157 patients, 55.4% of whom were women, were in the highest (worse) level (a score of 15 or greater, assumed to include only depressed patients); 159 patients, of whom 49.7% were women, were in the middle level (a score of 8-14); and 158, of whom 41.8% were women, were in the lowest level (7 or less, non-depressed patients only).

Patients in the highest level had more severe motor impairment and worse cognitive function than those in the lowest levels, even after taking DAT scan results into account.

Of note, no differences were found in DAT scores across the three groups, suggesting that “depression in de novo [Parkinson’s] does not require striatal dopamine depletion,” the researchers wrote.

Over a median follow-up of 47 months — ranging between four and 107 months — two movement disorder specialists adjusted the doses of Parkinson’s medications at three-to-six-month intervals.

Depressed patients required higher levodopa-equivalent doses — the amount of levodopa that has a similar effect as the medication taken — than non-depressed individuals after taking age, gender, and initial motor deficit severity into account.

“These results demonstrate that depression in de novo Parkinson’s is associated with motor deficit severity at baseline and dose of Parkinson’s medications during follow-up,” the researchers wrote.

Among the study’s limitations, the team mentioned not differentiating between patients with persistent depression during follow-up from those who reached a non-depressed status, as well not evaluating Parkinson’s progression.