Persistent apathy predicts faster functional decline in Alzheimer’s disease

A new study sheds light on how behavioral symptoms are related to daily functioning in people with Alzheimer’s disease. Researchers found that individuals with persistent apathy—characterized by diminished motivation and reduced emotional engagement—tend to experience a faster loss of independence over time. While people with Alzheimer’s disease can show different clusters of behavioral symptoms, apathy stood out as a particularly strong predictor of functional decline. The findings were published in The Journal of Neuropsychiatry and Clinical Neurosciences.

Alzheimer’s disease is a progressive brain disorder that affects memory, thinking, and behavior. As the disease advances, people often lose the ability to perform everyday tasks, such as managing finances or preparing meals. While memory loss is the most widely recognized symptom, many people with Alzheimer’s also experience changes in mood and behavior. These changes, known as neuropsychiatric symptoms, can include apathy, depression, agitation, delusions, and hallucinations. These symptoms can be distressing for both patients and caregivers and have been linked to worse outcomes, such as faster cognitive decline and earlier nursing home placement.

To better understand how behavioral symptoms influence the course of Alzheimer’s disease, researchers from multiple institutions analyzed data from the National Alzheimer’s Coordinating Center, which compiles information from Alzheimer’s research centers across the United States. They wanted to know whether clusters of behavioral symptoms—such as people who mainly show depression and apathy, or those who exhibit multiple symptoms—were linked to differences in how quickly someone’s ability to function declines over time. They also asked whether specific symptoms might be more predictive of decline than broader symptom patterns.

“We have been studying neuropsychiatric symptoms in dementia for some time and have always wondered if specific symptoms or specific individuals who manifest clusters of symptoms may be suitable targets for interventions for preventing and delaying functional decline,” said study author Carolyn W. Zhu, a professor and data core lead at the Alzheimer’s Disease Research Center at the Icahn School of Medicine at Mount Sinai.

The researchers included nearly 9,800 participants who had been diagnosed with either mild cognitive impairment or Alzheimer’s disease at the start of the study. All participants were over the age of 50 and had at least one follow-up visit over the course of up to five years. People with very mild or very severe dementia at the start were excluded. The average age of the sample was about 74 years old, and most participants were white and highly educated.

To track everyday functioning, researchers used a standard tool called the Functional Assessment Questionnaire. This questionnaire asks whether a person has difficulty with common activities, such as handling money, remembering appointments, or cooking. The responses are provided by someone who knows the participant well, such as a spouse or adult child. Higher scores on this scale indicate more difficulty with daily functioning.

Behavioral symptoms were assessed by expert clinicians at each visit. These clinicians reported whether the participant was currently showing symptoms such as apathy, depression, hallucinations, or agitation. The researchers looked at whether these symptoms were present at baseline, and whether they appeared intermittently or persistently over time.

Using a statistical method called latent class analysis, the team identified four main clusters of participants based on their symptom profiles at the start of the study. The largest group, which made up nearly half the sample, had few or no behavioral symptoms. A second group, comprising about 35% of participants, had high rates of apathy and depression. A third group, about 13%, showed multiple symptoms including agitation and irritability, but not hallucinations. The smallest group—just under 3%—showed high levels of all symptoms, including psychosis, and was labeled the “complex” group.

These symptom clusters were associated with differences in how well people were functioning at the beginning of the study. People in the asymptomatic group had better functional abilities than those in the other groups. However, over time, the rate of decline in functioning did not differ significantly between the groups. In other words, being in a certain symptom cluster did not predict how fast someone would lose the ability to carry out everyday tasks.

To look more closely at individual symptoms, the researchers then examined whether the presence and persistence of each symptom predicted functional decline, even after accounting for which cluster the person belonged to. Apathy stood out as a key factor. People who were rated as persistently apathetic over time experienced a much faster rate of functional decline than those who never had apathy.

Even those who showed apathy intermittently declined more quickly than those who never had the symptom. In contrast, other symptoms such as depression, disinhibition, and irritability were not linked to faster decline once apathy and other factors were taken into account.

The study also found that delusions and agitation were linked to faster decline, but the effect was smaller than that seen for apathy. Hallucinations were associated with worse function at baseline, but not with a faster rate of decline over time.

To better understand whether these findings applied to people in earlier versus later stages of the disease, the researchers conducted a separate analysis of people with mild cognitive impairment and those with full dementia. The results were consistent: apathy predicted faster decline in both groups, regardless of other symptoms.

“Our results showed that after taking into consideration other individual symptoms and different symptom clusters, apathy continued to be strongly associated with accelerated functional decline in dementia patients,” Zhu told PsyPost.

These findings support earlier research showing that apathy is a common and persistent symptom in Alzheimer’s disease and may play a central role in the progression of the illness. Apathy affects more than motivation—it can reduce a person’s interest in social engagement, make them less likely to initiate activities, and impair their ability to follow through on tasks. This diminished drive can make it harder to maintain independence in everyday life, even in the absence of severe memory problems.

Brain imaging studies suggest that apathy is linked to dysfunction in specific brain regions involved in motivation and reward processing, such as the prefrontal cortex and basal ganglia. Some researchers have proposed that apathy may reflect damage to circuits that are distinct from those that underlie memory loss, which may help explain why it can be an early and independent predictor of functional decline.

The results of this study suggest that clinicians should pay particular attention to signs of apathy in people with Alzheimer’s disease or mild cognitive impairment. While other symptoms like agitation or hallucinations often draw more attention because they are disruptive or alarming, apathy may have a more consistent impact on a person’s ability to function independently over time.

There are some limitations to the study. The participants were drawn from specialized research centers and were generally more educated and healthier than the general population. The assessments of symptoms were based on clinician judgment, which, while informed, may vary between clinicians. In addition, the study’s observational design means that it can identify associations but not prove causation.

Still, the large sample size, long follow-up period, and detailed symptom tracking provide strong support for the conclusion that apathy plays a significant role in functional decline. This finding has practical implications. Apathy is relatively easy to observe and measure in clinical settings. Detecting it early may help identify people at higher risk of losing independence and offer a window of opportunity for intervention.

“It is perhaps unsurprising that apathy, which is characterized by reduced motivation and independent goal-directed activity, should be so strongly associated with functional decline over time,” Zhu said. “However, its impact on function, which appears to be more significant than other more dramatic neuropsychiatric symptoms that often dominate clinicians’ time and attention, is likely under-appreciated in many clinical settings.”

“We believe that enhancing medical education for primary care providers who serve most patients with dementia, to improve awareness of neuropsychiatric symptoms in those with mild cognitive impairment and dementia may be a worthwhile strategy to providing patient centered care with better prediction of prognosis and targeted approaches for treatment and management.”

The study, “Understanding the Role of Neuropsychiatric Symptom in Functional Decline in Alzheimer’s Disease,” was authored by Carolyn W. Zhu, Lon S. Schneider, Laili Soleimani, Judith Neugroschl, Hillel T. Grossman, Corbett Schimming, and Mary Sano.