The route to dementia can start early in life—as early as adolescence, according to a longitudinal study of Swedish men published in the August 12 JAMA Internal Medicine online. Peter Nordström and colleagues at Umeå University in Sweden plumbed a rich dataset of men who enlisted in the armed services the 1970s, when in their late teens. Three decades on, the researchers used national records to determine who among the men developed young-onset dementia, and correlated that with nine different risk factors. The top indicators were low cognitive function at conscription and treatment for alcohol intoxication.
Nordström was interested in young-onset dementia (YOD), or dementia diagnosed before the age of 65, because of the severe impact it can have on the lives of patients and their families. Some people with YOD are young enough to be still caring for their children. YOD includes several kinds of dementia, including early onset Alzheimer’s (EOAD), vascular dementia, alcohol dementia, and frontal lobe degeneration. Early onset AD, in particular, is thought to have a strong basis in genetics, but heritability is also believed to be important in other forms of early dementia, Nordström said. However, YOD encompasses both inherited and sporadic disease. The AD type of YOD is somewhat different from the sporadic AD that occurs in old age, Nordström told Alzforum. For example, while memory loss related to hippocampal pathology is the typical first AD symptom, the hippocampus is more often spared in younger people who may initially present with problems in language, executive, or visuospatial function (van der Flier et al., 2011, Murray et al., 2011).
Because YOD is relatively rare, a large population is necessary to find enough cases to analyze. The Swedish government mandated military service throughout the 20th century. During the study period, from 1969 to 1979, 497,844 young men, aged about 18, enlisted. After an average of 37 years passed, Nordström and colleagues found that 487 of those men were diagnosed with YOD. The average age at diagnosis was 54. Of these, 146 had AD, 92 vascular dementia, 69 alcohol-related dementia, and 33 frontal lobe degeneration. Another 147 had dementia of an unidentified type, underscoring the difficulty doctors have in categorizing YOD (Rossor et al., 2010).
This population differs from those in studies of older people with dementia, where AD and vascular dementia predominate, noted Hugh Hendrie of Indiana University in Indianapolis. Hendrie was not involved in the study. Part of the reason, he noted, is that people with chronic alcoholism frequently die before they reach their 70s and 80s.
When Nordström and colleagues compared the men with YOD to those without, they identified nine independent risk factors: alcohol intoxication, use of antipsychotic medication, depression, dementia in the subject’s father, drug intoxication (besides alcohol), stroke, and at conscription low cognitive function, low height, and high systolic blood pressure. The researchers estimated that together, these factors account for 68 percent of the dementia risk in this population. Other dementia risk factors not assessed include diabetes, physical inactivity, and cranial bleeding, noted Deborah Levine of the University of Michigan in Ann Arbor, who penned a commentary accompanying the article in JAMA Internal Medicine.
The strongest predictors of future YOD were low cognitive function and alcohol intoxication. The military assessed cognition based on ability to understand written instructions, word recall, identifying a 3D object based on 2D pictures, and problem-solving ability. Nordström and colleagues calculated that those men who scored in the lowest tertile cognitively, and who had at least two other risk factors, were 20 times more likely to develop YOD than men with the highest cognition and no other risk factors. Nordström speculated that people who score high in cognition in their teens have better cognitive reserve, and might be able to keep functioning despite minor insults such as stroke, compared to those with a relatively low cognitive reserve to start with. Cognitive reserve similarly protects older adults against late-onset Alzheimer’s disease (see ARF related news story).
Severe alcohol intoxication, as a risk factor for YOD, could be related to the brain damage it can cause, Nordström said. The study “does shed light upon the deleterious effects of heavy drinking in a younger population that you tend not to see when you look at very old populations,” Hendrie said. Unfortunately, he noted, it would be difficult to identify and treat young people at risk for chronic alcoholism early on, because many young people binge drink.
The study authors looked at parental dementia as a risk factor, and found only the father’s status had a statistically significant effect on YOD in their sons. Nordström was uncertain why only the father’s dementia was important. He was surprised heritability accounted for a similar proportion of risk for all kinds of dementia studied, not just early onset AD, and that overall less than 5 percent of YOD risk was due to genetics. “Perhaps genetic factors are not as important as we previously thought,” Nordström said.
However, Hendrie noted that when the AD group was analyzed on its own, the only significant risk factors were family history, depression or antidepressant use, and antipsychotic use. Use of those medications, he commented, could be due to the onset of YOD symptoms or concern due to a family history of dementia. He argued that family history remains the major risk factor for early onset AD, and therefore many of these early cases could be familial. Certainly, he said, some types of EOAD are well known to be dominantly inherited.
As for the other dementia types, vascular dementia was associated with all of the nine risk factors, except for blood pressure. Alcohol dementia correlated with father’s dementia, alcohol and drug intoxication, depression, stroke, and antipsychotic use. Frontal lobe degeneration was linked to paternal dementia, depression, and antipsychotic treatment.
One factor conspicuously absent from Nordström’s list is socioeconomic status. The researchers did consider income and education, but neither of these reached significance in the final tally. Socioeconomic status certainly contributes to dementia risk, noted Hilkka Soininen of the University of Eastern Finland in Kuopio, who was not involved in the study, in an email to Alzforum. For example, Hendrie suggested, poor children might be exposed to lead, which affects the developing brain.
Nordström’s study underscores the idea that dementia risk begins to build up early, even in adolescence. “From the day we are born, I think we could influence these risk factors,” said Nordström, though he said this purely observational study offers no specific suggestions for how to do so. Stroke risk is dependent on many lifestyle factors, noted Soininen. The American Heart Association reports that modifiable stroke risk factors include diet, physical inactivity, and exposure to cigarette smoke (Goldstein et al., 2011). In the case of late-onset dementia, doctors and researchers are examining a variety of potentially beneficial lifestyle changes, such as diet, exercise, and social activity, but young-onset dementia has received less attention (see ARF related news story, ARF related news). One of the most important results of the current work, Hendrie and Nordström agreed, was the indication that alcohol abuse can lead to very early dementia.—Amber Dance
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