TBI Linked to Earlier Alzheimer's, Autopsy Data Confirm

Deborah Brauser

March 19, 2018

Traumatic brain injury (TBI) plus loss of consciousness (LOC) lasting longer than 5 minutes is associated with earlier onset of Alzheimer's disease (AD), new research suggests.

A study of more than 2100 patients with autopsy-confirmed AD showed that age at symptom onset was about 2 years earlier for those who had sustained a previous TBI plus LOC vs those who had never sustained a TBI, and the age of dementia diagnosis was almost 3 years earlier.

More stringent diagnostic criteria showed an even greater difference, with symptom onset and dementia diagnosis both occurring 3.6 years earlier in the TBI plus LOC group.

"This is the first study to use autopsy-confirmed cases, supporting previous investigations that used clinical criteria for the diagnosis of AD," write the investigators, led by Jeff Schaffert, University of Texas (UT) Southwestern Medical Center, Dallas.

"The importance of that is because patients with a clinical diagnosis of Alzheimer's actually may, or may not, have the disease. Dementia can be caused by a variety of conditions, although Alzheimer's is the most common," principal investigator, C. Munro Cullum, PhD, professor of psychiatry, neurology, and neurosurgery, and chief neuropsychologist at the Brain Institute, UT Southwestern, told Medscape Medical News.

Although this isn't a definitive study, "it's a step in the right direction," he added.

The findings were published online in Neuropsychology.

Another Puzzle Piece

"There have been a number of reports over the years that serious TBI did seem to pose a risk factor for dementia later in life, but not much is known about less severe injuries. So we wanted to start to understand this," said Cullum.

"Also, there's so much in the media now, so much concern about concussion and later life effects and so many chronic traumatic encephalopathy [CTE] discussions and worries, that we really just wanted to add one more piece to the puzzle," he added.

The investigators published a study last year that evaluated the clinical diagnosis of AD.

"We found that there was about a 2 and a half  year earlier onset" of AD in individuals who had a history of a head injury with at least a 5-minute LOC, said Cullum. "And we wanted to see if that actually held in a pathologically confirmed sample."

The investigators used data from the National Alzheimer's Coordinating Center Uniform Data Set and Neuropathology Data Set, which were collected from AD centers across the United States and included clinical and autopsy information for healthy individuals and those with cognitive impairment.

For this study, they assessed information on 2133 participants from 32 AD centers. Based on answers to specific questions, 1956 participants reported never having had a TBI and 197 reported at their first visit that they had had a remote/inactive TBI with no ongoing chronic deficits. "Remote/inactive" was defined as having sustained the TBI at least 1 year earlier.

Compared with individuals who never had a TBI (control group), those with TBI plus LOC had a significantly earlier symptom onset (adjusted average age, 70.37 vs 68.02 years, respectively; P = .01) and earlier diagnosis of dementia (77.01 vs 74.18 years; P = .002).

The investigators then used "more stringent neuropathological criteria," such as a CERAD neuritic plaque score of frequent and Braak neurofibrillary tangle stages of at least 5 to 6.

"Among cases with the highest probability of dementia due to AD, a 3.6 year earlier onset and diagnosis…was observed" in the TBI plus LOC group vs the control group (both P < .001), the researchers report.

What About Kids?

"When we got into the details of the severity of the Alzheimer pathology, it suggested some link with severity of pathology and old history of traumatic brain injury. So it does appear to be a risk factor for earlier onset of [AD]," said Cullum.

However, "we were looking at correlations here. So there's no causal relationship and we cannot predict individual cases," he noted. "But certainly as we learn more about dementia, and Alzheimer's in particular, it's important to understand what some of the risk factors are."

Study limitations included the investigators' reliance on patient reports of having experienced a past TBI with an LOC greater than 5 minutes, with no information on when the TBI occurred. And the investigators didn't have any information on whether length of LOC itself plays a part in the association with AD onset.

"The available data didn't tell whether a person had a 5-minute or 10-minute loss of consciousness. Again, this was more a correlational study, but certainly it adds to the mounting literature suggesting some sort of relationship that we don't fully understand yet," said Cullum.

He noted in a press release that even with these findings, he wouldn't suggest that parents need to keep their kids out of sports because of a fear that a concussion will lead to dementia.

"We don't know who is at risk, so we certainly don't want to alarm people. I'd rather see kids out there being active and playing sports than being sedentary and doing nothing. Their risks from that are probably greater [for health problems] than for participating in sports, whether there's contact or not," Cullum said.

The study was funded by grants from the UT Southwestern Alzheimer's Disease Center and the Texas Alzheimer's Research and Care Consortium. The database used in the study was funded by grants from the National Institute on Aging/National Institutes of Health. The study authors have disclosed no relevant financial relationships.

Neuropsychology. Published online February 1, 2018. Abstract

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