Hip Fracture in Older People Without Dementia May Be Sign of Undiagnosed Alzheimer’s

Abnormal levels of amyloid-beta and tau protein — two hallmarks of Alzheimer’s disease — were detected in the cerebrospinal fluid of older  individuals without dementia who were hospitalized for hip fractures, a study shows.

These findings suggest that alterations that can cause diminished balance in older people may underly both increased risk of hip-fracturing falls and Alzheimer’s disease, with hip fracture itself being a potential sign of undiagnosed Alzheimer’s.

The study, “Abnormal CSF amyloid-β42 and tau levels in hip fracture patients without dementia,” was published in the journal PLOS One.

One of the consequences of falls is hip fracture, with most (97%) occurring as the result of a fall. Hip fracture is associated with several complications including prolonged rehabilitation, loss of independence, and a one-year mortality of 26%. This suggests that a serious condition, linked with the fall that triggered the fracture, could be undiagnosed.

While mounting evidence suggests that Alzheimer’s is linked with gait disorder and falls in older adults without dementia, few studies have examined the prevalence of Alzheimer’s in these patients.

Researchers at the Johns Hopkins University School of Medicine evaluated a group of hip fracture patients for underlying Alzheimer’s pathology as shown by the presence of specific biomarkers in the cerebrospinal fluid (CSF) — the fluid that surrounds the brain and spinal cord. The team also wanted to determine how often this pathology is observed in hip fracture patients without dementia.

Researchers analyzed CSF samples from 168 patients — mean age 82 and mostly women (74%) — enrolled in the randomized STRIDE clinical trial (NCT00590707).

STRIDE, short for “A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients” took place at the Johns Hopkins Hospital and intend to observe which effects sedative medicines given during hip surgery have on peoples’ thinking processes after they wake up.

Researchers tested patients’ CSF for established biomarkers of Alzheimer’s disease, namely the two forms of amyloid-beta protein (Aβ42 and Aβ40)  phosphorylated tau (the protein responsible for neurofibrillary tangles observed in the brain of Alzheimer’s patients) and total levels of tau protein.

Before surgery, patients took the Mini-Mental State Exam, and their family members or caregivers completed the short form of the Informant Questionnaire on Cognitive Decline in the Elderly. Both tests were designed to assess mental state, memory and cognition. Based on these tests, and additional parameters collected from the patient and caregivers, participants were given a Clinical Dementia Rating (CDR) scoring.

“We studied a group of patients without a clinical diagnosis of dementia, meaning that many of our study participants were active and living independently without overt signs of Alzheimer’s disease,” Esther S. Oh, MD, said in a press release. Oh is associate director of the Johns Hopkins Memory and Alzheimer’s Treatment Center and the study’s lead author.

Patients with a CDR score of zero were considered to be healthy without dementia (70 patients). Those with a CDR of 0.5 had mild cognitive symptoms (81 participants), while a CDR score above 1.0 was considered a stage of early dementia (13 patients) and a score of 2.0 of moderate dementia (four patients).

The results showed that 86% of the entire group had abnormal amyloid-beta levels. Abnormal levels of phosphorylated-tau and total-tau were observed in in 37% and 65% of participants, respectively.

Among those defined as cognitively normal (with a CDR score of zero), 88.6% had abnormal levels of any one of the biomarkers. This was observed in 98.8% of the patients with mild cognitive impairment (CDR of 0.5).

In fact, 68% of participants, from 65 to 74 years old and with a CDR score of zero, had abnormal amyloid-beta levels. This value is higher than in the general population, where rates of abnormal amyloid levels rate are around 23 to 32%.

Oh noted this study is not suggesting that every elder person who has a hip fracture has Alzheimer’s, or that everyone hospitalized for a hip fracture should undergo spinal fluid tests for disease biomarkers. However, these findings suggest that those who undergo hip repair surgery after a fall should be closely monitored for any signs of post-operative delirium or other mental or cognitive problems during recovery, as this may be a sign of underlying Alzheimer’s.

The team will continue to monitor the participants for a year after each surgery to assess signs of disease progression and dementia.