Signs of depression and apathy precede memory problems in Alzheimer’s disease, study shows

People who develop Alzheimer’s disease show signs of depression and apathy before they start to experience memory disturbances, says a US study that observed the natural time course of symptoms before the onset of symptomatic dementia.

Non-cognitive symptoms such as depression, apathy, and aggression are known to occur with advancing cognitive decline in Alzheimer’s disease, but information has been limited on whether these symptoms also precede dementia.

To find out more about the time course of symptoms in Alzheimer’s disease researchers followed up 2416 people aged 50 and older, using information from the National Alzheimer’s Coordinating Center’s Uniform Data Set from 2005 to 2013.1 This data set collects information from 34 Alzheimer’s Disease Centers across the United States.

All study participants were found to be cognitively normal at their first visit and had at least one additional visit after their initial assessment. Symptoms were assessed using standardised tools, including the Neuropsychiatric Inventory questionnaire and the Geriatric Depression Scale.

Results showed that people who went on to have dementia diagnosed (that is, with a clinical dementia rating above zero; n=1558) were twice as likely to have symptoms of depression in the preceding period as those who did not go on to reach this level of dementia (hazard ratio 2.09 (95% confidence interval 1.69 to 2.58, P<0.001)).

People with diagnosed dementia were also more likely to experience apathy (3.81 (2.79 to 5.20, P<0.001)) and irritability than those who did not go on to have dementia diagnosed.

Tracking non-cognitive symptoms over time showed three phases: first came irritability, depression, and changes in night time behaviour; next were anxiety, appetite changes, agitation, and apathy; and third were elation, motor disturbances, hallucinations, delusions, and disinhibition.

All participants showed increasing depression and other non-cognitive psychiatric symptoms with increasing age, but this rise occurred earlier and more quickly in people who went on to have dementia diagnosed.

“Our sample demonstrates significant non-cognitive declines associated with eventual progression to a clinical diagnosis of dementia,” said the research group, led by Catherine Roe, of the Department of Neurology at Washington University School of Medicine in St Louis, Missouri. They said that more research is needed to better understand the correlation between non-cognitive changes, healthy ageing, and different subtypes of dementia.

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