Understanding Depression Before and After Parkinson’s Disease and Lewy Body Dementia Diagnosis

Depression is a significant and often overlooked aspect of neurodegenerative disorders such as Parkinson’s disease (PD) and Lewy body dementia (LBD). Recent research has highlighted the strong link between these conditions and depression, both before and after diagnosis. Understanding this connection can improve early detection, patient care, and treatment outcomes. This blog explores the findings of a large-scale Danish study that analyzed depression trends in patients with PD and LBD compared with other chronic conditions, including rheumatoid arthritis, chronic kidney disease, and osteoporosis.

Depression in Parkinson’s Disease and Lewy Body Dementia

Parkinson’s disease is a progressive neurodegenerative disorder primarily affecting movement, while Lewy body dementia is characterized by both cognitive and motor impairment. Depression is one of the most common non-motor symptoms in these diseases, affecting an estimated 30 to 40 percent of patients. Comorbid depression in PD and LBD has been linked to faster disease progression, cognitive decline, higher disability, increased suicide risk, and overall mortality.

Neurobiological studies suggest that depression in these patients may be caused by disruptions in monoaminergic systems, including dopamine, serotonin, and norepinephrine, which play a key role in mood regulation. Cholinergic dysfunction, a hallmark of PD and LBD, may further impair emotional regulation and cognitive function, exacerbating depressive symptoms. Psychological and social factors, such as coping mechanisms, personality traits, and social isolation, can also influence the onset and severity of depression in these populations.

The Danish Study on Depression and Neurodegenerative Disease

A retrospective case-control study conducted in Denmark sought to quantify depression incidence before and after the diagnosis of PD and LBD. The study included 17,711 patients with PD or LBD, matched with up to three patients diagnosed with rheumatoid arthritis, chronic kidney disease, or osteoporosis. These conditions served as comparison groups to evaluate whether depression rates in PD and LBD were higher than in other chronic illnesses.

Patients were followed for up to 10 years before and 10 years after their diagnosis. Incident depression was identified through prescription records for antidepressants specifically indicated for depression or through psychiatric hospital diagnoses. This approach ensured that only clinically relevant depression cases were included.

Key Findings of the Study

The study revealed several important trends:

1. Increased Depression Before Diagnosis
   Patients with PD and LBD experienced substantially higher rates of depression even before their formal diagnosis. Specifically, depression incidence was elevated as early as 7 to 8 years prior to diagnosis. During this prediagnostic period, 13.1 percent of PD patients and 16.9 percent of LBD patients experienced incident depression. By comparison, the rates in patients with rheumatoid arthritis, chronic kidney disease, and osteoporosis were significantly lower, ranging from 5.6 to 7.8 percent.
2. Persistent Depression After Diagnosis
   Depression rates remained higher in PD and LBD patients for up to five years following diagnosis. In the post-diagnostic period, 7.9 percent of PD patients and 8.5 percent of LBD patients developed depression, compared with 5 to 6 percent in the control groups. This finding indicates that depression is not only an early symptom but continues to affect patients long after their diagnosis.
3. Higher Depression Rates in Lewy Body Dementia
   Notably, patients with LBD consistently showed higher pre- and post-diagnostic depression rates than those with PD. This may reflect the more aggressive disease course, increased cognitive decline, and higher allostatic load in LBD, making patients more susceptible to mood disturbances.
4. Comparison with Other Chronic Conditions
   By comparing PD and LBD patients with individuals diagnosed with RA, CKD, and osteoporosis, researchers accounted for disability-related depression. While RA and CKD are associated with significant disability, osteoporosis typically causes less functional impairment. The study found that even when controlling for disability, PD and LBD patients experienced markedly higher depression rates, supporting the idea that depression may be a direct manifestation of neurodegenerative changes rather than solely a reaction to physical disability.

Clinical Implications

The findings of this study have important implications for healthcare professionals.

Early Detection of Parkinson’s Disease and Lewy Body Dementia

The study suggests that depression may serve as an early marker of neurodegenerative disease. Incident depression occurring in older adults, particularly those around 75 years of age, should prompt clinicians to consider the possibility of prodromal PD or LBD. Early recognition allows for closer monitoring of both motor and non-motor symptoms, potentially enabling timely interventions and more comprehensive patient management.

Importance of Screening and Treating Depression

Given the persistent elevated risk of depression after diagnosis, regular screening for depressive symptoms should be integrated into routine care for PD and LBD patients. Early detection and treatment of depression can improve quality of life, reduce cognitive decline, and potentially slow disease progression. Interventions may include pharmacological treatments such as antidepressants or non-pharmacological therapies, including cognitive-behavioral therapy and psychosocial support.

Implications for Care Planning

Recognizing depression as a core feature of PD and LBD can inform care planning and resource allocation. Mental health support should be considered as essential as physical therapy and neurological care. A multidisciplinary approach involving neurologists, psychiatrists, psychologists, and primary care providers can ensure comprehensive management of both motor and non-motor symptoms.

Biological Mechanisms Linking Depression and Neurodegeneration

Several neurobiological mechanisms may explain the increased incidence of depression in PD and LBD patients.

• Monoaminergic Dysfunction: Dopamine, serotonin, and norepinephrine systems are disrupted in PD and LBD, leading to mood disturbances.
• Cholinergic Deficits: Reduced cholinergic activity in the hippocampus and prefrontal cortex can impair emotional regulation and cognitive function, contributing to depressive symptoms.
• Neurodegenerative Burden: Progressive neuronal loss, especially in brain regions responsible for mood and cognition, may directly trigger depressive symptoms.
• Disease-Related Stress: The psychological burden of subtle prodromal symptoms, functional impairment, and uncertainty about disease progression can increase vulnerability to depression.

Limitations of the Study

While the Danish study provides valuable insights, several limitations should be acknowledged.

1. Selection Bias
   Patients diagnosed solely by private practitioners were not included, potentially overrepresenting more severe cases of PD and LBD.
2. Depression Measurement
   Depression was identified based on prescriptions or hospital diagnoses, which may not capture cases treated exclusively through non-pharmacological interventions or general practice.
3. Control Group Characteristics
   RA and CKD were used as active controls, but differences in age and sex distribution could influence results. Osteoporosis acted as a passive control, though patients often received hospital care after fractures, potentially increasing depression risk temporarily.
4. Detection Bias
   Patients with PD and LBD may have more frequent healthcare visits, increasing the likelihood of depression detection compared with other chronic conditions.
5. Generalizability
   Findings are based on Danish population registers, and results may not fully apply to populations with different healthcare systems or demographics.

Despite these limitations, the consistent trend of elevated depression rates before and after diagnosis supports the hypothesis that depression is a significant non-motor feature of PD and LBD.

Recommendations for Healthcare Professionals

Based on the study findings, healthcare professionals should consider the following recommendations:

1. Screen for Depression Early
   Assess depressive symptoms in older adults, particularly those presenting with late-onset depression, as this may indicate early neurodegenerative changes.
2. Integrate Mental Health into Neurological Care
   Routine mental health evaluations should be part of PD and LBD management to facilitate timely treatment and support.
3. Educate Patients and Caregivers
   Raise awareness among patients and families about the risk of depression and its potential impact on disease progression and quality of life.
4. Consider Multidisciplinary Approaches
   Combine neurology, psychiatry, psychology, and primary care expertise to provide holistic care addressing both motor and non-motor symptoms.
5. Monitor Disease Progression
   Depression may serve as a marker for disease progression or complications. Monitoring mood changes can provide insights into the overall course of PD and LBD.

Conclusion

Depression is a prevalent and clinically significant feature of Parkinson’s disease and Lewy body dementia. The Danish nationwide study demonstrates that depression can occur up to eight years before diagnosis and persists for at least five years afterward. Compared with other chronic conditions, PD and LBD show substantially higher rates of incident depression, supporting the hypothesis that depression is an early manifestation of neurodegenerative processes.

Healthcare professionals should recognize depression as a core feature of PD and LBD, integrate routine screening and treatment into care, and remain vigilant for late-onset depression as a potential early sign of these neurodegenerative diseases. Early recognition and intervention can improve patient outcomes, enhance quality of life, and potentially inform the development of disease-modifying therapies.

Sources

1. Rohde C, Langeskov-Christensen M, Bastrup Jørgensen L, Borghammer P, Østergaard SD. Depression preceding and following the diagnosis of Parkinson’s disease and Lewy body dementia. BMJ Open. 2025;38(6).
2. Reijnders JSAM, Ehrt U, Weber WEJ, et al. A systematic review of prevalence studies of depression in Parkinson’s disease. Mov Disord. 2008;23:183–189.
3. Gallagher DA, O'Sullivan SS, Evans JR, et al. Predictors of depression in Parkinson’s disease: a prospective cohort study. Mov Disord. 2010;25:1150–1157.

Disclaimer

This blog is intended for informational purposes only and is not a substitute for professional medical advice. If you or someone you know is experiencing depression or symptoms of Parkinson’s disease or Lewy body dementia, consult a qualified healthcare professional for diagnosis and treatment. The information provided here is based on research studies and may not apply to all individuals.