Schizophrenia is a chronic disorder characterized by symptoms that include hallucinations, delusions, abnormalities in the verbal expression of thought, diminished social interactions, diminished motivation, and difficulties with cognitive tasks involving attention, memory, and planning. The long term course of this disorder varies. Some individuals, with the help of appropriate medication and social support, can live independently, be employed, and enjoy friends and hobbies. For others, however, the symptoms are difficult to manage and interfere with most aspects of their lives, often leading to disability and early death. It is also not uncommon for persons with schizophrenia to use street drugs and alcohol, and chronic abuse of alcohol or illicit drugs negatively impacts their long term outcome.

Although cognitive symptoms involving attention and memory are common in persons with schizophrenia, such symptoms tend to be stable and non-progressive through middle age. Whether schizophrenia is associated with an increased risk for a progressive dementia later in life has been the focus of several research studies, but the results so far have been inconclusive. Prospective studies addressing this issue are difficult to perform given the need for a large study population and the long period of time between an initial diagnosis of schizophrenia and the onset of dementia.

A recent study published in JAMA Psychiatry by Anette Ribe and colleagues took advantage of the large national health registries in Denmark to examine the relationship between schizophrenia and onset of dementia. They collected data on over 2.8 million people who were 50 years of age or older at some point between 1995 and 2013. Over 20,600 people had or developed schizophrenia during the study period. Over 136,000 developed a progressive dementia, as evidenced by a progressive decline in cognitive function, during the same period.

The investigators found that the risk of developing a progressive dementia before the age of 65 was 1.8% for people with schizophrenia compared to only 0.6% for those without schizophrenia. By the age of 80, people with schizophrenia remained at higher risk for dementia but the difference between the 2 populations was less striking: 7.4% for people with schizophrenia and 5.8% for people without schizophrenia. These data indicate that the people with schizophrenia had a greater risk not only for developing dementia but also for developing it at a younger age. In fact, 22.4% of the individuals with schizophrenia who went on to develop dementia (211 of 944) were diagnosed with dementia before 65. In comparison, only 6.3% of the people with dementia who did not have schizophrenia were diagnosed with dementia at this relatively early age. The specific type of dementia that these individuals developed was not well characterized in this study. Many had clinical features seen in persons with Alzheimer’s disease.

Persons with schizophrenia are known to have an elevated risk for several medical conditions, including obesity, diabetes, hyperlipidemias, and cardiovascular disease. These medical conditions are all associated with increased risk for dementia. When the investigators controlled for co-morbid medical disorders, they found that most did not contribute to the higher risk for dementia observed in persons with schizophrenia. One exception was co-morbid substance abuse, which appeared to be responsible for a small portion of the increased risk.

Why do individuals with schizophrenia develop dementia at an increased rate as well as at an earlier age than those without schizophrenia? Do brain abnormalities that contribute to the cognitive dysfunction in schizophrenia also predispose to progressive dementia later in life? This is an area for future research. Is it possible that there are subtypes of schizophrenia that are associated with a much higher rate of developing dementia? 

It is believed that a healthy lifestyle that includes exercise, good diet, positive social interactions, and maintenance of healthy blood pressure and cholesterol levels may help in minimizing certain types of dementia. It is likely that this would also hold true in persons with schizophrenia. Healthier lifestyles, including avoidance of abused drugs and alcohol, would also likely diminish the risk of early death in persons with schizophrenia.

This column was written by Eugene Rubin MD, PhD and Charles Zorumski MD.

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