Traumatic Brain Injury (TBI) poses a significant health burden worldwide, affecting approximately 70 million individuals annually, regardless of the underlying mechanisms of injury (1). Considering all ages and severities in Europe, the crude incidence of TBI varies from 47.3 per 100,000 to 694 per 100,000 inhabitants in country-level studies (2). TBI exhibits two distinct incidence peaks: in children and young adults (typically aged 18–40 years) and older adults (over 60 years). The first peak primarily results from high-risk behaviors and activities, such as motor vehicle accidents and sports injuries, while the second peak is mainly due to falls, which are more common in the elderly population (3, 4). These age-related patterns underscore the need for targeted prevention strategies to reduce TBI risk in these vulnerable groups (5, 6).

Several studies have revealed that older age is a significant negative prognostic factor after TBI (7–11). These issues justify the need for further research using standardized protocols, comprehensive assessments, longer follow-up periods, and larger sample sizes to understand better how age affects TBI outcomes, ultimately leading to better use of resources and improved patient care. Furthermore, diagnostic testing and treatment interventions may vary among different age groups, and a lower level of management intensity could explain the association between older age and poor outcomes (12). Indeed, elderly TBI patients are less likely to receive the activation of trauma teams and advanced imaging, both crucial for early and accurate diagnosis and intervention (13). This conservative approach extends to critical care procedures, where ventilator support and intracranial pressure (ICP) monitoring decrease significantly with older age (13). Surgical treatments, which can be life-saving, are also less frequently performed in elderly patients. Decompressive craniectomy, in particular, is rarely conducted in individuals over 50 despite similar injury severities observed in younger cohorts (12, 14, 15). This decline in treatment intensity is often driven by assumptions about the frailty and limited recovery potential of older patients, which can lead to poorer outcomes.

However, not all TBI patients can be considered using such assumptions. For instance, if adequate acute and post-acute care is provided, a mild TBI may have a much better outcome than moderate and severe TBI, even when older age is considered (13, 16). In fact, inadequate therapy may lessen the chances of survival and recovery for older TBI patients, blunting the potential recovery of such patients, especially the so-called “younger” elderly (17, 18).

The therapy intensity level (TIL) is a composite score that assesses the graded interventions for treating intracranial pressure (ICP) in TBI, with a higher TIL indicating a higher tier of treatments in managing ICP (19, 20). The TIL evaluation includes different treatments such as sedation, osmotic therapy, hypoventilation, hypothermia, cerebrospinal fluid drainage, and surgery. The rationale for using this score is that interpreting ICP is impossible without understanding the therapy’s efforts (20). While prior studies (7–11) have shown that older age is a significant predictor of poor outcomes in TBI patients, few have examined how varying levels of treatment intensity influence these outcomes, especially in elderly patients. This study addresses this critical gap in the literature by investigating how varying levels of TIL affect neurological outcomes in TBI patients across different age groups.

While it is well established that older age is associated with worse outcomes, our study is one of the first to explore whether high-intensity treatment can mitigate these negative effects, particularly in the elderly. By focusing on the interaction between age and therapy intensity, we offer new insights into how personalized, aggressive treatment can improve outcomes even in patients traditionally considered high-risk due to their age.

In this study, we found that age ≥ 80 years was independently associated with worse neurological outcomes and that age ≥ 50 years was associated with increased in-hospital mortality. However, in a exploratory hypothesis generating subgroup analysis considering patients who received high-intensity treatment, age did not increase the likelihood of poor outcomes at 3 months or in-hospital mortality. In contrast, among patients who received lower-intensity therapy, age ≥ 80 years was independently associated with poor outcomes and age ≥ 50 years was independently associated with in-hospital mortality.

Currently, the rate of hospital admissions due to TBI is higher in the elderly population (≥ 65 years old) than in other age groups (31). This patient population is more susceptible to falls, which usually cause mass effect injuries, and they have more comorbidities and severe baseline cognitive or functional deficits (32), increasing the risk of post-recovery functional decline compared to younger patients (33). Indeed, older age has consistently been reported as a factor associated with unfavorable outcomes (34–37) and mortality (33, 38–40) in this setting. However, this association may be impacted by frailty, which represents the cumulative decline in physiological systems over a lifetime (13), making patients more vulnerable to further insults such as TBI and susceptible to poorer outcomes. A recent study has shown that older patients have higher frailty scores, and frailty was an independent determinant of poor outcomes (41). Previous studies have also demonstrated that older TBI patients, especially those without significant pre-existing comorbid conditions (42–44), can survive and recover, reinforcing that factors other than age are important when prognosticating these patients (14, 18, 45). Moreover, a study from the CENTER-TBI database recently highlighted that patients receiving high-intensity treatments may have better outcomes despite the initial severity of the illness (46). This finding has also been confirmed in the SYNAPSE-ICU study, which showed that ICP monitoring and higher TIL were associated with lower mortality, despite older patients not being specifically analyzed in detail for outcomes, based on age groups (47). Similarly, Skaansar et al. demonstrated that a low management intensity strategy correlated with higher 30-day mortality in elderly patients (12).

Despite these findings, older TBI patients are less frequently admitted to the ICU, receive less intensive monitoring (such as invasive ICP), and undergo fewer life-saving interventions like mechanical ventilation or surgery, as highlighted in previous studies (11, 48–51). For instance, randomized clinical trials of surgical interventions in TBI, such as decompressive craniectomy, often exclude patients over the age of 60–65 years (52, 53). The clinical implications of this study, particularly for elderly patients, deserve close attention. Aggressive interventions such as decompressive craniectomy in this population carry inherent risks due to frailty, pre-existing comorbidities, and polypharmacy. These factors likely contribute to the exclusion of older patients from clinical trials, as studies have demonstrated higher mortality and complication rates in this age group (52, 53). Frailty and functional status play a pivotal role in the recovery potential of elderly patients and must be carefully balanced against the potential benefits of invasive procedures (54–56). Geriatric trauma outcome scores (GTOS) and tools like the GERtality Score can help quantify these risks (54–56). These scoring systems, validated in predicting mortality and poor outcomes in elderly trauma patients, aid clinicians in identifying which patients might benefit from high-intensity treatments (57). Additionally, socioeconomic status (SES) has been shown to significantly influence healthcare access, with lower SES often correlating with poorer outcomes due to limited access to post-acute care and rehabilitation services (58).

Additionally, patients included in the BEST-TRIP randomized clinical trial that assessed the impact of ICP monitoring on the outcome of TBI patients were young, with a median age of 29 years, despite not having an upper age limit as an exclusion criterion, further demonstrating that elderly patients are often not offered specific modalities of monitoring and treatment (59). Nevertheless, successful rehabilitation and community reintegration are possible for older TBI patients when adequately treated (49, 60–62).

When assessing the prognosis of brain-injured patients, a so-called “self-fulfilling prophecy” occurs, e.g., when a comatose patient is given a poor prognosis, leading to the withholding of life-sustaining care based on that prediction, which directly results in the patient’s poor outcome (e.g., death) (63). This phenomenon is common in the elderly population but can also be observed in younger patients. A recent study found that among 1,400 patients with severe TBI, some who were taken off life support may have survived and regained some level of independence a few months later, as predicted by a complex mathematical model (64). Neurological recovery and improvement of disorders of consciousness require time and intensive rehabilitation (65) in both elderly and young patients (66). This situation points to a cyclical, self-fulfilling prophecy where clinicians predict poor outcomes based on previously published data in the context of limited therapy, including ICU admission for cases deemed unsalvageable. This assumption leads to withdrawing life support, which increases the likelihood of poor outcomes and further decisions to remove life support (64). In our exploratory analysis, the differences between high and low TIL subgroups may suggest a benefit in treating implementing high intensity treatment to an elderly population. However, this was an exploratory analysis of a retrospective registry and we are unable to ascertain what were the criteria used to decide the intensity of treatment applied to some elderly patients but not others, which may have introduced bias. Further studies are therefore required to investigate this hypothesis. In fact, whether a more proactive therapeutic approach could potentially decrease the high mortality rate and improve neurological outcomes among older TBI patients remains to be validated.

One might speculate that high-tier treatments for TBI patients are costly and not generally worth it compared to comfort care. However, this hypothesis has been contradicted by a study in which researchers developed a decision-analytical model to compare aggressive care, routine care, and comfort care. The study showed that aggressive care may be significantly less expensive up to the age of 80, after which it becomes more expensive than routine care (67). Nonetheless, even for 80-year-old patients, aggressive care may be reasonable depending on the patient’s baseline functional status. Although the p-value for interaction was not significantly different when analyzing the impact of age and TIL on measured outcomes, subgroup analyses were performed, as suggested in previous publications (68, 69). These analyses suggested the importance of age on outcomes in relation to the intensity of therapies used to lower ICP.

The advantage of our research lies in its detailed examination of how TIL interacts with age to influence outcomes in TBI patients. While many studies have considered age an independent predictor of worse outcomes, few have explored the mitigating effects of aggressive treatment, especially in older populations. Our findings indicate that high-intensity treatment can improve neurological outcomes and survival even in elderly patients traditionally considered high-risk due to their age. These results challenge conservative treatment practices and suggest that age should not be the sole factor in determining treatment intensity. This study’s focus on the interaction between age and TIL provides new insights into optimizing care for elderly TBI patients and supports a more personalized, aggressive treatment approach.

Our study has several limitations. The retrospective design may introduce biases and limit the ability to establish causal relationships between the identified predictors and clinical outcomes. Additionally, it restricted our analysis to short-term outcomes, which are not ideal for the neurocritical population. Despite our large sample size, the results may lack generalizability as it is a single-center study. Furthermore, the assessment of TIL may be subject to variability in measurement techniques and lacks standardized cut-offs for defining high and low TIL subgroups. The TIL score refers primarily to the intensity of treatment focused on intracranial hypertension, which, while an essential cause of mortality and unfavorable outcomes in TBI patients, does not account for other complications, such as hospital-acquired infections that could have impacted our results. Importantly, we did not evaluate the economic burden associated with patient care across different age groups. Such an analysis requires specialized expertise and falls beyond the scope of our study. Finally, we were unable to assess mortality due to withdrawal of care, which may have influenced our findings, and we did not retrieve the SES of patients. Additionally, we did not evaluate patients’ functional status before admission or their frailty score. Our study also had a limited number of patients aged 80 years or more, which may have reduced the power of the study to detect significant outcomes in this age group and adequately evaluate the interaction between age categories and TIL.

Our findings suggested that while advanced age is independently associated with worse outcomes in TBI patients, treatment intensity can modify this relationship. High-intensity therapy could lead to better outcomes, even in patients aged 80 years or older, suggesting that age alone should not be a limiting factor in treatment decisions. A personalized, potentially aggressive approach to improve survival and neurological outcomes across age groups, particularly for elderly needs to be further investigated.