The Diagnostic Challenge of Psychiatric Symptoms in Neurodegenerative Disease: Rates of and Risk Factors for Prior Psychiatric Diagnosis in Patients With Early Neurodegenerative Disease

Langley Porter, Department of Psychiatry, University of California, San Francisco, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 02/2011; 72(2):126-33. DOI: 10.4088/JCP.10m06382oli
Source: PubMed


To identify rates of and risk factors for psychiatric diagnosis preceding the diagnosis of neurodegenerative disease.
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.
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.
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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Available from: Joshua D Woolley, Apr 25, 2014
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    • "The patients may present with a wide range of symptoms, including prominent neuropsychiatric symptoms that often mimic other psychiatric disorders. Initial psychiatric diagnoses, such as psychosis or depression, are common (Gregory and Hodges, 1996; Passant et al., 2005; Woolley et al., 2011). "
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    ABSTRACT: Background: Frontotemporal dementia (FTD) constitutes a spectrum of neurodegenerative disorders associated with degeneration of, predominantly, the frontal and temporal lobes. The clinical heterogeneity is evident, and early diagnosis is a challenge. The primary objectives were to characterize psychotic symptoms, initial clinical diagnoses and family history in neuropathologically verified FTD-patients and to analyze possible correlations with different neuropathological findings. Methods: The medical records of 97 consecutive patients with a neuropathological diagnosis of frontotemporal lobar degeneration (FTLD) were reevaluated. Psychotic symptoms (hallucinations, delusions, paranoid ideas), initial diagnosis and family history for psychiatric disorders were analyzed. Results: Psychotic symptoms were present in 31 patients (32%). There were no significant differences in age at onset, disease duration or gender between patients with and without psychotic symptoms. Paranoid ideas were seen in 20.6%, and hallucinations and delusions in 17.5% in equal measure. Apart from a strong correlation between psychotic symptoms and predominantly right-sided brain degeneration, the majority of patients (77.4%) were tau-negative. Only 14.4% of the patients were initially diagnosed as FTD, while other types of dementia were seen in 34%, other psychiatric disorders in 42%, and 9.2% with other cognitive/neurological disorders. The patients who were initially diagnosed with a psychiatric disorder were significantly younger than the patients with other initial clinical diagnoses. A positive heredity for dementia or other psychiatric disorder was seen in 42% and 26% of the patients respectively. Conclusions: Psychotic symptoms, not covered by current diagnostic criteria, are common and may lead to clinical misdiagnosis in FTD.
    International Psychogeriatrics 12/2014; 27(04):1-9. DOI:10.1017/S1041610214002580 · 1.93 Impact Factor
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    • "The appropriate clinical diagnosis of bvFTD can be diffi cult and can represent a real challenge. Certain neuropsychiatric symptoms and changes in behaviour and personality, especially when they are very subtle, can be ignored or attributed to a primary psychiatric condition in about half of bvFTD patients (Woolley et al., 2011). This is likely the result of several different factors, one of which is the overlap between the symptomatic dimensions of bvFTD and several psychiatric disorders, especially in the early stages of bvFTD. "
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    ABSTRACT: Abstract Several factors make diagnosis of a possible behavioural variant of frontotemporal dementia (bvFTD) particularly challenging, especially the overlap of certain symptomatic dimensions such as apathy, disinhibition, depression, anhedonia, stereotyped behaviour, and psychosis between bvFTD and several psychiatric disorders that appear in late adulthood. We discuss the most frequent psychiatric conditions that can simulate early bvFTD symptoms, including late onset bipolar disorder, late onset schizophrenia-like psychosis, late onset depression, and attention deficit hyperactivity disorder in middle and older age.
    International Review of Psychiatry 04/2013; 25(2):159-67. DOI:10.3109/09540261.2013.769939 · 1.80 Impact Factor
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    • "Among all neurodegenerative disorders, frontotemporal dementia (FTD) particularly distinguishes itself because behavioral changes are the hallmark of this group of disorders. Approximately 50% of patients with behavioral variant FTD (bvFTD) receive a psychiatric diagnosis (most frequently major depressive disorder, schizophrenia, and bipolar disorder) prior to correct diagnosis [1]. Understanding the manner in which bvFTD may present as a neuropsychiatric syndrome is paramount to avoid erroneous diagnoses and provide the best treatment for patients. "
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    ABSTRACT: Earlier reports of chromosome 9p-linked frontotemporal dementia (FTD) with amyotrophic lateral sclerosis (ALS) kindreds observed psychosis as a prominent feature in some patients. Since the discovery of chromosome 9 open reading frame 72 (C9orf72) hexanucleotide expansions as a cause of FTD and ALS, research groups and consortia around the world have reported their respective observations of the clinical features associated with this mutation. We reviewed the recent literature on C9orf72-associated FTD and ALS with focus on the neuropsychiatric features associated with this mutation, as well as the experience at University of California, San Francisco. The results and methodologies varied greatly across studies, making comparison of results challenging. Four reports found that psychotic features (particularly delusions) were frequent among mutation carriers, particularly when present early during the disease course, suggesting that this symptom category may be a marker for the mutation. Disinhibition and apathy were the most commonly reported early behavioral symptoms, but these may not be helpful in distinguishing carriers and noncarriers because of the symptoms' frequency in sporadic behavioral variant FTD. Other neuropsychiatric features were reported in different frequencies across studies, suggesting either a similar behavioral phenotype in carriers and noncarriers or reflecting the heterogeneity in clinical presentation of behavioral variant FTD due to C9orf72 expansions. Further studies with larger cohorts will be necessary to determine the neuropsychiatric presentation associated with this mutation.
    Alzheimer's Research and Therapy 10/2012; 4(5):38. DOI:10.1186/alzrt141 · 3.98 Impact Factor
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