Could neuropsychiatric symptoms herald Alzheimer's disease? Sometimes, according to a paper in the January 14 Neurology online. Catherine Roe and colleagues at the Washington University School of Medicine in St. Louis found that while problems such as irritability and depression are common and tend to develop in a particular order, they occur sooner in people who progress to dementia.

Scientists have long known that depression, apathy, anxiety, and aggression accompany AD, but these psychiatric symptoms also appear in people with mild cognitive impairment as well as in those who stay cognitively healthy (see Tariot et al., 1995; Lyketsos et al., 2002). Roe and colleagues asked if these symptoms develop differently—for example, in a distinct order—among people headed for dementia.

To find out, first author Mary Clare Masters and colleagues examined data from the National Alzheimer’s Coordinating Center Uniform Data Set, which drew from 34 AD centers across the United States. Records spanned September 2005 to March 2013. From this dataset, a total of 1,218 healthy people aged 50 or older progressed to a Clinical Dementia Rating (CDR) of 0.5 or higher. Another 1,198 people matched for age, education, and ApoE4 status stayed cognitively healthy. The researchers then compared data on the Neuropsychiatric Inventory Questionnaire (NPI-Q), which allows a spouse or other partner to report things such as irritability and apathy, and the Functional Activities Questionnaire, which assesses activities of daily living. The self-reported Geriatric Depression Scale was used to assess indicators of depression.

During the eight years of clinical observation, items on the NPI-Q cropped up in the same order for both people who stayed healthy and people who developed dementia. First came disturbances in nighttime behavior, irritability, and depression. Anxiety, apathy, agitation, and appetite changes followed next. In people who progressed to a CDR of greater than 0, however, these symptoms appeared sooner. Few in either group developed feelings of elation, motor disturbances, hallucinations, or delusions, which are NPI-Q items seen in advanced Alzheimer’s (see Eustace et al., 2002).

According to the functional activities scale, people en route to cognitive problems struggled with daily living activities such as paying bills, shopping, and preparing meals, while people who remained cognitively normal did not. Self-reported depression was similar in both groups, although in the cognitively declining group partners reported earlier depression. Others may spot these changes better than the patients themselves, the authors suggested.

In some cases, neuropsychiatric changes occurred before patients developed any cognitive impairment, Roe told Alzforum, suggesting that these shifts could begin in the preclinical phase of AD. “That helps reinforce the notion that this psychopathology can exist across a wide portion of the disease-severity spectrum,” said Pierre Tariot of Banner Alzheimer’s Institute, Phoenix. “Emerging neuropsychiatric signs and symptoms by themselves might be a tip-off to emerging dementia.”

Not everyone who develops some sort of psychological symptom is headed for dementia, Roe said. However, if an otherwise cognitively healthy person or his or her relatives complain about irritability or lack of energy, the doctor might look for early signs of dementia in addition to the usual list of potential causes, she told Alzforum.

The possibility that psychological symptoms could precede dementia begs the question of how the two relate, said Anton Porsteinsson of the University of Rochester, New York. Is one driving the other, or are they both consequences of underlying neuropathological changes? Likewise, would psychological intervention make a difference with cognition? Future studies will answer those questions, he said.—Gwyneth Dickey Zakaib


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Paper Citations

  1. . The Behavior Rating Scale for Dementia of the Consortium to Establish a Registry for Alzheimer's Disease. The Behavioral Pathology Committee of the Consortium to Establish a Registry for Alzheimer's Disease. Am J Psychiatry. 1995 Sep;152(9):1349-57. PubMed.
  2. . Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA. 2002 Sep 25;288(12):1475-83. PubMed.
  3. . The Uniform Data Set (UDS): clinical and cognitive variables and descriptive data from Alzheimer Disease Centers. Alzheimer Dis Assoc Disord. 2006 Oct-Dec;20(4):210-6. PubMed.
  4. . A longitudinal evaluation of behavioural and psychological symptoms of probable Alzheimer's disease. Int J Geriatr Psychiatry. 2002 Oct;17(10):968-73. PubMed.

Further Reading


  1. . Early noncognitive change in Alzheimer's disease and healthy aging. J Geriatr Psychiatry Neurol. 1994 Oct-Dec;7(4):199-205. PubMed.

Primary Papers

  1. . "Noncognitive" symptoms of early Alzheimer disease: a longitudinal analysis. Neurology. 2015 Feb 10;84(6):617-22. PubMed.