The Diagnostic Challenge of Psychiatric Symptoms in Neurodegenerative Disease: Rates of and Risk Factors for Prior Psychiatric Diagnosis in Patients With Early Neurodegenerative Disease
Open accessAbstract
OBJECTIVE: To identify rates of and risk factors for psychiatric diagnosis preceding the diagnosis of neurodegenerative disease. METHOD: Systematic, retrospective, blinded chart review was performed of 252 patients with a neurodegenerative disease diagnosis seen in our specialty clinic between 1999 and 2008. Neurodegenerative disease diagnoses included behavioral-variant frontotemporal dementia (n = 69), semantic dementia (n = 41), and progressive nonfluent aphasia (n = 17) (all meeting Neary research criteria); Alzheimer's disease (n = 65) (National Institute of Neurologic and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association research criteria); corticobasal degeneration (n = 25) (Boxer research criteria); progressive supranuclear palsy (n = 15) (Litvan research criteria); and amyotrophic lateral sclerosis (n = 20) (El Escorial research criteria). Reviewers remained blinded to each patient's final neurodegenerative disease diagnosis while reviewing charts. Extensive caregiver interviews were conducted to ensure accurate and reliable diagnostic histories. For each patient, we recorded history of psychiatric diagnosis, family psychiatric and neurologic history, age at symptom onset, and demographic information. RESULTS: A total of 28.2% of patients with a neurodegenerative disease received a prior psychiatric diagnosis. Depression was the most common psychiatric diagnosis in all groups. Behavioral-variant frontotemporal dementia patients received a prior psychiatric diagnosis significantly more often (50.7%; P < .001) than patients with Alzheimer's disease (23.1%), semantic dementia (24.4%), or progressive nonfluent aphasia (11.8%) and were more likely to receive diagnoses of bipolar disorder or schizophrenia than were patients with other neurodegenerative diseases (P < .001). Younger age (P < .001), higher education (P < .05), and a family history of psychiatric illness (P < .05) increased the rate of prior psychiatric diagnosis in patients with behavioral-variant frontotemporal dementia. Cognitive, behavioral, and emotional characteristics did not distinguish patients who did or did not receive a prior psychiatric diagnosis. CONCLUSIONS: Neurodegenerative disease is often misclassified as psychiatric disease, with behavioral-variant frontotemporal dementia patients at highest risk. While this study cannot rule out the possibility that psychiatric disease is an independent risk factor for neurodegenerative disease, when patients with neurodegenerative disease are initially classified with psychiatric disease, the patient may receive delayed, inappropriate treatment and be subject to increased distress. Physicians should consider referring mid- to late-life patients with new-onset neuropsychiatric symptoms for neurodegenerative disease evaluation.
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Average diagnostic delay from symptom onset in bvFTD is up to 5-6 years.
“average diagnostic delay is up to 5-6 years from symptom onset (Woolley et al. , 2011; van Vliet et al. , 2013; Ducharme et al. , 2017).”
From Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders (2020) · cites this paper as Woolley et al., 2011
The Results (Referral Period; page unavailable) report a mean delay of 33.3 months between psychiatric and neurodegenerative diagnoses. This supports a diagnostic delay, but it is not an average of 5–6 years from symptom onset in bvFTD; the reported mean covers patients with prior psychiatric diagnoses across neurodegenerative diseases. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAround 50% of patients with bvFTD receive a prior psychiatric diagnosis.
“Around 50% of patients with bvFTD receive a prior psychiatric diagnosis”
From Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders (2020) · cites this paper as Woolley et al., 2011
Symptomatic overlap with primary psychiatric disorders, misdiagnosis and diagnostic delay hamper adequate characterization of the disease course in bvFTD.
“Furthermore, symptomatic overlap with primary psychiatric disorders (PPD), misdiagnosis and diagnostic delay all hamper an adequate characterization of the disease course in bvFTD (Woolley et al., 2011).”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Woolley et al., 2011
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- Authors
- Woolley, J. D., Khan, B. K., Murthy, N. K., Miller, B. L., & Rankin, K. P.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Woolley, Josh D.
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2011-02-15
- Volume
- 72
- Issue
- 02
- Pages
- 126-133
- ISSN
- 0160-6689 (ISSN-L)
- PMC
- PMC3076589
- OpenAlex
- W1978093816
- Cited by
- 549
- References
- 35
- Citations by year
- 2026: 24 · 2025: 43 · 2024: 58 · 2023: 51 · 2022: 43 · 2021: 57 · 2020: 70 · 2019: 34 · 2018: 31 · 2017: 29 · 2016: 33 · 2015: 24 · 2014: 16 · 2013: 15 · 2012: 19
- FWCI
- 11.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Centre for Applied Research in Cancer Control
- National Institute on Aging (AG-19724, P01AG017586, AG023501, 5-P01 AG19724, P01-AG19724, P01AG019724, P50AG023501)
- National Institute of Mental Health (R25MH060482)
- National Cancer Institute (R01CA094143)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- psychiatric symptoms, neurodegenerative diseases, behavioral variant frontotemporal dementia, Alzheimer's disease, semantic dementia, progressive nonfluent aphasia, corticobasal degeneration, progressive supranuclear palsy, amyotrophic lateral sclerosis, depression, misdiagnosis, psychiatric comorbidity, risk factors, family history of mental illness, age and education, bipolar disorder
- MeSH terms
- Adjustment Disorders, Aged, Anxiety Disorders, Mental Disorders, Bipolar Disorder, Cross-Sectional Studies, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Schizophrenia, Schizophrenic Psychology, Comorbidity, Age of Onset, Neurodegenerative Diseases, Neurocognitive Disorders, Genetic Predisposition to Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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