The rate of misdiagnoses of patients who have Alzheimer's disease (AD) is extremely high, especially for those with psychosis, new research suggests.
The study, which included data on more than 900 patients from the National Alzheimer's Coordinating Center (NACC), showed that almost 25% of participants received either a false positive (12.1%) or a false negative (11.9%) AD diagnosis.
In addition, more patients with psychosis received false negative AD diagnoses compared to their counterparts without psychosis. Further, the rate of misdiagnoses of Lewy body dementia (LBD) instead of AD was five times higher for those with, vs those without, psychosis.
"The rate of misdiagnosis was quite high, at 24% overall. And, interestingly, patients who exhibited psychosis were more likely to be misdiagnosed with other forms of dementia," coinvestigator Winnie Qian, a master's student in the neuroscience program at St Michael's Hospital, Toronto, Canada, told Medscape Medical News.
Winnie Qian
"Psychosis is perhaps more common in Alzheimer's disease than clinicians think," added Qian. "So they should keep the diagnosis of Alzheimer's more in mind when these types of patients present to the clinic."
The findings were published in the September issue of Alzheimer's and Dementia.
Tip of the Iceberg?
Approximately 36% of all AD patients have delusions, and 18% have hallucinations, note the investigators.
"Psychosis can be a symptom of Alzheimer's disease, but it is a defining clinical feature in other types of dementia," lead author Corinne Fischer, MD, director of the Memory Disorders Clinic at St Michael's Hospital, said in a press release.
"Consequently, clinicians are more reluctant to diagnose a patient with [AD] when they present with delusions or hallucinations," she added.
In the study, the researchers assessed NACC data for 961 individuals who received a clinical diagnosis of probable AD while alive or whose autopsy results met the National Institute of Aging (NIA)–Reagan Institute neuropathologic criteria for AD. These data were collected between September 2005 and May 2012 at 29 centers in the United States.
Patients were considered to have received a correct diagnosis if they had been given a clinical diagnosis of probable AD and their autopsy results yielded a "high likelihood of dementia due to AD," using NIA-Reagan criteria (n = 731).
Those who received the clinical diagnosis but did not meet neuropathologic criteria were classified as "false positives" (n = 116), whereas those who met the criteria but who did not receive a clinical diagnosis were classified as "false negatives" (n = 114).
The delusion and hallucination items on the Neuropsychiatric Inventory Questionnaire were used to determine those with psychosis (n = 355).
Of the patients with psychosis, 173 had delusions, 103 had delusions and hallucinations, and 79 had hallucinations only.
Results showed higher rates of false negative diagnoses for AD in the group that had any psychosis compared to those without psychosis, but lower rates of false positive diagnoses.
Table 1. Rates of Diagnosis and Misdiagnosis of AD in Patient Groups
| Type of Diagnosis | Patients With Psychosis (%) | Patients Without Psychosis (%) | P Value |
| Correct diagnosis | 80.0 | 73.8 | < .05 |
| False negative | 13.5 | 10.9 | Not significant |
| False positive | 6.5 | 15.3 | < .01 |
After multiple adjustments, the difference in false negative diagnoses between the groups became significant (11.3% vs 4.3%, respectively, P < .01). The adjusted rates of false positive diagnoses remained the same, as shown in the Table 1.
Type of psychosis did not affect overall misdiagnosis rates.
For the participants with false negative diagnoses who met criteria for AD at autopsy, patients in the three psychosis subgroups were five times more likely to receive a clinical diagnosis of LBD compared with those without psychosis. "Possible AD" was the most common misdiagnosis received by those without psychosis.
Table 2. Faulty Diagnoses Within Psychosis, Nonpsychosis Subgroups
| Clinical Diagnosis | Without Psychosis (%) | Delusions (%) | Hallucinations (%) | Hallucinations + Delusions (%) |
| LBD | 10.6 | 55.0 | 54.5 | 58.8 |
| Vascular dementia | 13.6 | 0 | 9.1 | 23.5 |
| Possible AD | 60.1 | 25.0 | 18.2 | 5.9 |
Vascular pathology was the underlying cause of dementia in the majority of individuals with a false positive AD diagnosis who did not have psychosis. For patients with psychosis who were misdiagnosed on neuropathologic grounds, the most common classification of their condition was "other."
Overall, the findings suggest that "in the presence of psychosis in a patient with progressive cognitive decline and no other clinical features suggestive of another form of dementia, a diagnosis of AD should be given more consideration," write the investigators.
In such cases, "existing symptomatic treatments, such as cholinesterase inhibitors, should be potentially prescribed."
Qian noted in the release that the researchers focused on the final clinical diagnosis after years of follow-up, "so the rate of misdiagnosis we described is the rate under ideal conditions.
"This means that it should be considered a minimum. If you extrapolate that and apply it to the general population, the magnitude of the problem could be much greater," she said.
"Many dementia patients never receive a definitive clinical diagnosis while they're alive," added Dr Fischer. "The hope is that by understanding which factors can lead to a misdiagnosis, we can [become] more accurate."
Access to Better Tools "Critical"
James A. Hendrix, PhD, director of global science initiatives at the Alzheimer's Association, told Medscape Medical News this study "underscores how challenging" it is to determine specific causes of dementia and how the presence of psychosis makes the process even more difficult.
Dr James Hendrix
"This is precisely why it is critical for dementia specialists to have access to a variety of tools for diagnosing Alzheimer's disease and other dementias," said Dr Hendrix.
Having the ability to objectively measure biological changes that would suggest whether or not a disease is present, such as the build-up of amyloid plaques and tau tangles for AD, would be very helpful, he added.
"The Alzheimer's Association is leading or supporting numerous initiatives to make these kinds of advanced diagnostic tools more widely available in doctors' offices," said Dr Hendrix.
These initiatives include the ongoing, large-scale Imaging Dementia–Evidence for Amyloid Scanning study, known as IDEAS, and tau PET imaging and fluid analyses.
"When you have the tools to make a more specific diagnosis, you improve the ability to provide the most appropriate care," he concluded.
The study was funded by a grant from the Canadian Institutes of Health Research. The NACC database is funded by a grant from the National Institute of Aging/National Institutes of Health. The study authors have disclosed no relevant financial relationships.
Alzheimers Dement. 2017;3:385-392. Full text
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Cite this: Psychosis May Up Alzheimer's Misdiagnosis Rate - Medscape - Jul 19, 2017.
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