BOSTON—Patients misdiagnosed with Alzheimer’s disease are less likely to be depressed than patients correctly diagnosed with Alzheimer’s disease, according to research presented at the 2013 Alzheimer’s Association International Conference. Patients misdiagnosed with Alzheimer’s disease also tend to have less cognitive impairment, less functional impairment, and less severe behavioral symptoms than patients correctly diagnosed with the disease.

Approximately 18% of persons misdiagnosed with Alzheimer’s disease were treated with a potentially inappropriate medication, according to Haya Ascher-Svanum, PhD, research fellow at Eli Lilly and Co. For the purposes of the analysis, inappropriate treatment was defined as treatment with unnecessary drugs or without appropriate drugs. A sensitivity analysis indicated that the rate of inappropriate treatment could be as high as 67%.

Analysis of Data From Alzheimer’s Disease Centers
Because of a lack of effective clinical tools, neurologists can only diagnose Alzheimer’s disease definitively through a neuropathologic examination at autopsy. The sensitivity and specificity of clinical diagnoses of Alzheimer’s disease vary according to the neuropathologic criteria used, and false positives may account for 12% to 23% of patients diagnosed with Alzheimer’s disease.

Dr. Ascher-Svanum and her colleagues examined data from the National Alzheimer’s Coordinating Center Uniform Data Set (NACC-UDS) to determine whether individuals misdiagnosed with Alzheimer’s disease differed from correctly diagnosed patients in terms of sociodemographic characteristics, health history, cognitive impairment, functional status, or neuropsychiatric symptoms. The investigators also sought to determine the extent of potentially inappropriate medication use among misdiagnosed patients.

The NACC-UDS is a longitudinal database with standardized cognitive, behavioral, and functional data. Data were collected during participants’ annual visits to 31 National Institute on Aging Alzheimer’s Disease Centers between 2005 and 2010. Dr. Ascher-Svanum’s group focused on 526 subjects. Clinical diagnosis of Alzheimer’s disease did not match neuropathologic diagnosis at autopsy for 88 of these subjects. Misdiagnosed participants were diagnosed postmortem with various conditions, including frontotemporal dementia, dementia with Lewy bodies, and cerebrovascular disease.

Misdiagnosed Participants Had Less Cognitive Impairment
The mean age at study enrollment of misdiagnosed participants was approximately 84, compared with approximately 79 for accurately diagnosed subjects. Misdiagnosed patients also were less likely to be married and more likely to live alone. Approximately 57% of misdiagnosed individuals were married, compared with 71% of accurately diagnosed individuals. About 17% of misdiagnosed patients lived alone, compared with 4% of accurately diagnosed patients.

In addition, the two groups of patients differed in the severity of cognitive impairment and in their health histories. Mean score on the Mini-Mental State Examination was 19.46 for misdiagnosed participants and 12.93 for accurately diagnosed participants. The mean time since the onset of cognitive decline at the first visit was 6.30 years for misdiagnosed patients and 7.81 years for accurately diagnosed patients. One-quarter of misdiagnosed subjects were cognitively normal, compared with approximately 8% of accurately diagnosed subjects.

Approximately 47% of misdiagnosed individuals had a cardiovascular condition, compared with 31% of accurately diagnosed individuals. Mean score on the Functional Activities Questionnaire was 20.96 for misdiagnosed participants and 24.52 for accurately diagnosed participants. Mean score on the Neuropsychiatric Inventory Questionnaire (NPI-Q) was 4.84 for misdiagnosed patients, compared with 6.18 for accurately diagnosed patients. Approximately 20% of misdiagnosed patients had depression, compared with 37% of accurately diagnosed patients.

After controlling for sociodemographic characteristics, time since onset of cognitive decline, probable diagnosis of Alzheimer’s disease at baseline, and dementia severity, the researchers found that the two groups significantly differed on only one variable. Misdiagnosed individuals were less likely to be depressed than accurately diagnosed individuals.

Study Sample May Not Be Representative
Several factors may influence the interpretation of the results, according to the authors. For example, data were collected at Alzheimer’s Disease Centers, which are predominantly in urban areas and recruit mostly Caucasian participants, so the study findings may not be generalizable to patients evaluated in routine clinical practice. The study may have underestimated the prevalence of potentially inappropriate medication use because of infrequent assessments, the small number of assessments available after the visit during which probable Alzheimer’s disease was first recorded, and the high proportion of study participants with a diagnosis of likely Alzheimer’s disease before enrollment. In addition, depression was assessed using a single NPI-Q item because many data were missing on subjects’ Geriatric Depression Scale scores.

Nevertheless, the study “highlights the importance of making an accurate diagnosis of Alzheimer’s disease in clinical practice, and especially ruling out Alzheimer’s disease, to help reduce unnecessary treatment and increase appropriate therapy for patients’ conditions,” according to Dr. Ascher-Svanum. “Additional research is needed to demonstrate the link between inappropriate treatment and adverse health outcomes in misdiagnosed patients with cognitive decline.”

—Erik Greb
Senior Associate Editor

Misdiagnosis of Alzheimer’s Disease Is Linked to Less Severe Dementia Profile