Increased risk of immune-related hepatitis among adolescent and young adults (AYAs) with melanoma during immunotherapy with checkpoint inhibitors (ICIs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9584-9584
Author(s):  
Alicia Darwin ◽  
Damon R. Reed ◽  
Tawee Tanvetyanon
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Age Groups ◽  
The Elderly ◽  
Age Related ◽  
Increased Risk ◽  
Melanoma Patients ◽  
Grade 3 ◽  
Elderly Cohort ◽  
Investigational Agents

9584 Background: Melanoma is the second most common malignancy affecting AYA patients after lymphoma. Nevertheless, AYA melanoma does constitute a minority of all melanoma cases. Additionally, the AYA population is not well represented in prospective clinical trials, including immunotherapy trials. While previous research has demonstrated the efficacy of ICIs across age groups, it remains unclear if toxicity profiles will be similar. In the general population, age-related changes in the immune milieu result in differential incidences of autoimmune diseases by age. This study aims to compare the toxicity profile between a cohort of AYA melanoma versus elderly melanoma patients receiving ICI therapy. Methods: In this single NCCN institutional study, electronic medical records of melanoma patients treated with ICIs between 01/2007-01/2019 were reviewed. Subjects receiving concurrent investigational agents or chemotherapy were excluded. The AYA cohort included those aged 15-40 years. The elderly cohort included those aged ≥65 years. Adverse events were coded according to CTC-AE version 5.0. Multivariable logistic regression analyses were performed. Results: Analyses included 184 treatment courses. In the AYA cohort (N = 57), median age at ICI initiation was 28.8 years (range: 17.9-39.3). In the Elderly cohort (N = 127), median age at ICI initiation was 72.3 years. More AYA patients (28.1% AYA vs. 7.9% Elderly) received ICI combination regimens. The most common adverse events amongst both cohorts were transaminitis (23.4%), rashes (49.5%), and diarrhea/colitis (20%). Incidences of pneumonitis, colitis, hypothyroidism, and hypophysitis did not differ significantly between cohorts. However, the AYA cohort experienced a higher incidence of transaminitis (38.6% AYA vs. 16.5% Elderly, p =0.001 ) and increased occurrence of treatment related hospitalization (26.3% AYA vs. 7.1% Elderly, p <0.001 ). Moreover, a higher proportion of severe grade ≥3 transaminitis occurred in the AYA group (27.3% AYA vs. 9.5% Elderly, p =0.004). While occurrence of transaminitis was significantly associated with combination ICIs, the association between AYA status and transaminitis remained significant after adjusting for ICI regimen (OR 2.75, 95% CI: 1.3-5.8). There was a trend toward shorter time to transaminitis onset among the AYA than Elderly cohort (median 53.0 vs. 74.5 days [non-parametric p= 0.28]). To date, median survival has not been reached in both groups ( p= 0.09). Conclusions: In this large cohort of AYA melanoma patients treated with ICI, we found a significantly higher incidence of immune-related transaminitis than in the Elderly cohort. Other immune-related AEs were comparable between cohorts. This finding was independent of ICI regimen. Further investigation will be needed to understand these differences between the AYA and Elderly cohorts.

Liver injury by immune checkpoint inhibitors in patients with hepatocellular carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 341-341 ◽  
Author(s):  
Nicola Personeni ◽  
Tiziana Pressiani ◽  
Antonio Capogreco ◽  
Arianna Dal Buono ◽  
Antonio D'Alessio ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Subsequent Treatment ◽  
Drug Induced ◽  
Increased Risk ◽  
Grade 3

341 Background: In patients with hepatocellular carcinoma (HCC) and baseline liver dysfunction, hepatic immune-related adverse events (HIRAEs) during immunotherapy have not been adequately characterized and their impact on subsequent treatment outcomes is not known. Methods: 40 patients with advanced/unresectable HCC and Child Pugh score A have been enrolled in first and second-line clinical trials of anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAbs). HCC etiologies were: hepatitis C (32.5%), hepatitis B (7.5%), alcohol abuse (27.5%), other (32.5%). 7 received anti-PD-1 mAbs alone and 33 received combined regimens that included anti-PD-1 mAbs plus either anti-cytotoxic T lymphocyte antigen 4 (30.4%) or tyrosine kinase inhibitors (TKIs) (54.5%), or both (15.1%). We reviewed their liver function tests and HIRAEs onset was related to time to treatment failure (TTF). Results: Overall, 12 patients (30%) developed grade ≥ 3 hepatitis according to Common Toxicity Criteria for Adverse Events v. 4.03, resulting in 4 cases of grade 2 drug-induced liver injury per DILI Working Group criteria. Time between therapy initiation and hepatitis onset was 1.4 months (0.4-2.8) and median peak aminotransferase (AT) level was 258 IU/L (85-869). Out of 6 permanent treatment discontinuations due to adverse events (AEs), 4 were linked to hepatitis. Higher AT median levels at baseline were significantly linked to grade ≥ 3 hepatitis compared with lower grades (95 IU/L vs. 36 IU/L, respectively; p = 0.008). Etiology, age, treatment did not predict HIRAEs onset. TTF in patients in patients with grade ≥ 3 hepatitis was shorter than in the whole cohort (1.4 vs. 3.8 months, p = 0.041), while overall survival did not differ (p = 0.125). Conclusions: We observed a 30% incidence of clinically significant HIRAEs. HIRAEs represent the most frequent AEs leading to treatment discontinuation in patients with HCC undergoing treatments with immune checkpoint inhibitors. Baseline AT levels may identify patients at increased risk of grade ≥ 3 hepatitis.

Comparison of efficacy and safety of checkpoint inhibitors in patients with genitourinary cancers aged below and above 75 years.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16101-e16101
Author(s):  
Gerald Bastian Schulz ◽  
Bernadett Szabados ◽  
Annabel Spek ◽  
Michael D. Staehler ◽  
Christian Stief ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Cancer Patients ◽  
Renal Cell ◽  
Urothelial Cancer ◽  
Checkpoint Inhibitors ◽  
The Elderly ◽  
Genitourinary Cancers ◽  
Grade 3

e16101 Background: Checkpoint-inhibitors have recently been introduced in the treatment of patients with genitourinary cancers. However, the use in elderly patients is controversial due to putative age-associated changes including the dysregulation of the immune system. We sought to investigate the safety and efficacy of immunotherapy in patients younger and older than 75 years of age. Methods: We conducted a retrospective review of patients with renal cell carcinoma and urothelial cancer treated with different immunotherapeutic agents between August 2015 and September 2018 at a high-volume single institution. Eligible patients received at least one cycle of single agent or a combination of checkpoint inhibitors as first or following treatment line. Immune-related adverse events (irAE) were graded using the NCI CTCAE v 4.0. Clinicopathological parameters including gender, cancer entity, ECOG, adverse events, comorbidities and response to treatment were stratified by age ≥ 75 vs. < 75 years and tested with a Pearson's chi-squared test. Additionally, we evaluated the impact of irAE on oncological outcome using the log-rank test. Results: 79 patients were identified, of those 27 (34.2%) were 75 years and older (15 renal cell carcinoma and 12 urothelial cancer patients) and 52 (65.8%) were younger than 75 years (39 renal cell carcinoma and 13 urothelial cancer patients). 2 complete responses were achieved in the elderly group and 6 in the younger group (p = 0.56). Disease control rate (stable disease, partial and complete response) was 48,1% in the elderly group and 53.8% in the younger group (p = 0.631). We observed a total of 30 irAEs (18 grade 1-2 and 12 grade 3-4), with an even distribution among the groups (≥75 years: 1 grade 4 AE; < 75 years: 12 grade 3-4 AEs). Except for ECOG ≥2 (p = 0.009) and ≥2 comorbidities (p < 0.001), there was no difference when groups were stratified by age. Both disease control rate and irAE did not differ between age subgroups. Occurrence of irAE showed no impact on oncological survival. Conclusions: The study demonstrates that patients over 75 years of age with renal cell and urothelial cancer treated with checkpoint-inhibitors respond with a good toxicity profile and an efficacy comparable with the younger population. irAE seem to have no impact on prognosis.

scholarly journals P539 Assessment of age as a risk factor for adverse events in patients from the tofacitinib ulcerative colitis clinical programme

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S460-S461
Author(s):  
G R Lichtenstein ◽  
B Bressler ◽  
S Vermeire ◽  
C Francisconi ◽  
N Lawendy ◽  
...  
Keyword(s):  
Risk Factor ◽  
Adverse Events ◽  
Multivariate Analyses ◽  
Age Groups ◽  
Older Age ◽  
Major Adverse Cardiovascular Events ◽  
Treatment Groups ◽  
Age Related ◽  
Increased Risk ◽  
Maintenance Study

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of UC. Safety and efficacy of tofacitinib were demonstrated in Phase (P)2/3 induction studies, a 52-week, P3 maintenance study, and are being further investigated in an ongoing, open-label, long-term extension (OLE) study.1,2 Here, we provide an updated analysis of age as a risk factor for adverse events (AEs) in the tofacitinib UC clinical programme.3 Methods Proportions of AEs and serious AEs (SAEs), and incidence rates (IRs; unique patients with events per 100 patient-years) for AEs of special interest (AESIs), were determined for two cohorts: the Maintenance Cohort (patients who received placebo or tofacitinib 5 or 10 mg twice daily [BID] in the maintenance study) and the Overall Cohort (all tofacitinib 5 or 10 mg BID-treated patients in the P2/P3/OLE studies; as of May 2019), stratified by age. Multivariable Cox proportional hazards regression analyses were performed to assess whether older age was associated with increased risk of AESIs in the Overall Cohort. Results In the Maintenance Cohort, IRs of AEs and SAEs were generally similar between treatment groups, with no age-related trend in the proportions of AEs in tofacitinib-treated patients. AESIs were infrequent in both treatment groups; however, herpes zoster (HZ; non-serious and serious) IRs were numerically higher in the ≥40 to &lt;50 and ≥50 years age groups for patients treated with tofacitinib 10 mg BID vs. placebo and tofacitinib 10 vs. 5 mg BID. In the Overall Cohort, IR of serious infections was generally similar between age groups, while IRs of opportunistic infections (OIs) and HZ (non-serious and serious), malignancy (excl. non-melanoma skin cancer [NMSC]), NMSC and major adverse cardiovascular events increased with increasing age. The IRs of HZ and NMSC were significantly greater in patients ≥50 years compared with patients &lt;30 years, and in patients ≥30 to &lt;40 years for NMSC. In multivariate analyses, older age was identified as a significant predictor of malignancy (excl. NMSC), NMSC and HZ. Conclusion In the Overall Cohort, there was a trend for an increase in the rates of OIs, HZ, malignancy (excl. NMSC) and NMSC with increasing age. In multivariate analyses, older age was associated with increased risk of malignancy (excl. NMSC), NMSC and HZ. The results of this analysis are generally consistent with previous studies suggesting older age may be associated with an increased risk of certain AESIs in patients with UC, and in some instances in the general population.4 References

scholarly journals Comparative Risk of Renal Adverse Events in Patients Receiving Immune Checkpoint Inhibitors: A Bayesian Network Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Kang Liu ◽  
Zhongke Qin ◽  
Xueqiang Xu ◽  
Ting Li ◽  
Yifei Ge ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cancer Therapy ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Increased Risk ◽  
The Difference ◽  
Grade 3

BackgroundImmune checkpoint inhibitors (ICIs) have brought a paradigm shift to cancer treatment. However, little is known about the risk of renal adverse events (RAEs) of ICI-based regimens, especially ICI combination therapy.MethodsWe carried out a network meta-analysis of randomized controlled trials (RCTs) to compare the risk of RAEs between ICI-based regimens and traditional cancer therapy, including chemotherapy and targeted therapy. Subgroup analysis was conducted based on tumor types.ResultsNinety-five eligible RCTs involving 40,552 participants were included. The overall incidence of RAEs, grade 3–5 RAEs, acute kidney injury (AKI), and grade 3–5 AKI was 4.3%, 1.2%, 1.3%, and 0.8%, respectively. Both ICI-based treatment regimens and traditional cancer therapy showed significantly higher risk of RAEs and AKI than the placebo. Among ICI monotherapy, anti-PD-1 (RR: 0.51, 95%CI: 0.29–0.91) was significantly safer than anti-CTLA-4 in terms of RAEs. Anti-CTLA-4 showed significantly higher toxicity than anti-PD-1 (RR: 0.33, 95%CI: 0.14-0.77), anti-PD-L1 (RR: 0.38, 95%CI:0.16-0.91), and anti-PD-1 plus anti-CTLA-4 (RR: 0.32, 95%CI: 0.12-0.87) in terms of grade 3-5 RAEs. The difference was not significant between ICI monotherapy and traditional cancer therapy, except that targeted therapy seemed the least toxic therapy in terms of the incidence of AKI. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1 (RR: 1.61, 95%CI: 1.02–2.56). The difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICI plus chemotherapy showed increased risk of both RAEs and AKI compared with ICI monotherapy, chemotherapy, and targeted therapy. The overall results remained robust in the meta-regression and sensitivity analyses.ConclusionsAmong ICI monotherapy, anti-CTLA-4 appeared to be associated with increased toxicity, especially in terms of grade 3–5 RAEs. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1. However, the difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICIs plus chemotherapy seemed to be the most toxic treatment regimen in terms of RAEs, AKI, and grade 3–5 AKI.Systematic Review RegistrationPROSPERO, identifier CRD42020197039.

Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
David C Goff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stroke Risk ◽  
Multivariable Analysis ◽  
The Elderly ◽  
Stroke Risk Factors ◽  
Age Related ◽  
Increased Risk ◽  
The Impact ◽  
Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

Abstract P329: White Matter Score Does Not Predict Post-tPA Hemorrhage in Elderly Patients Evaluated Acutely via Telestroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Muhammad Bilal Tariq ◽  
Shekhar Khanpara ◽  
Eliana Bonfante Mejia ◽  
Liang Zhu ◽  
Christy T Ankrom ◽  
...  
Keyword(s):  
White Matter ◽  
Elderly Patients ◽  
The Elderly ◽  
Periventricular White Matter ◽  
Severe Stroke ◽  
Age Related ◽  
Increased Risk ◽  
Symptomatic Intracranial Hemorrhage ◽  
Relationship Of ◽  
Patient Presentation

Background: While tPA may be safe in the elderly, increasing age appears to augment risk of post-tPA symptomatic intracranial hemorrhage (sICH). Age-related white matter changes (ARWMC) are associated with increased sICH. Patients evaluated for acute ischemic stroke (AIS) via telestroke (TS) may not have access to MRI to allow incorporation of microbleeds in tPA decisions. We assessed if increased CT-based ARWMC was associated with increased sICH in elderly patients. Methods: Patients 80 years and older who received tPA for AIS at spoke hospitals were selected from our TS network registry from 9/2015 to 12/2018. TS spoke CT scans from patient presentation were reviewed by three of the authors for periventricular white matter (PWMC) and deep white matter (DWMC) changes. Total ARWMC score, based on the Fazekas score, was collected. Total ARWMC score was either mild (0-2), moderate (3-4), or severe (5-6). PWMC and DWMC were either mild (0-1) or moderate-severe (2-3). Logistic regression adjusted for age, sex, race, ethnicity, NIHSS and premorbid mRS was used to analyze relationship of ARWMC scores with sICH and patient-outcomes. Results: Of 241 patients, median age overall was 86 years (IQR 83-90), and 66% were female. The overall median ARWMC score was 3 (IQR 2-5). Regression analysis showed that more severe ARWMC scores did not lead to higher frequency of post-tPA ICH (moderate OR 0.57, CI 0.19-1.71; severe OR 1.32, CI 0.48-3.65) including sICH (moderate OR 0.78, CI 0.21-2.94; severe OR 2.09, CI 0.62-7.02). Similarly, severe PWMC and DWMC were not associated with increased risk of post-tPA ICH (PWMC OR 1.31, CI 0.51-3.38; DWMC OR 1.25, CI 0.52-3.01), including sICH (PWMC OR 1.61, CI 0.51-5.08; DWMC OR 1.81, CI 0.65-5.01). In our cohort, older patients had no difference in hemorrhage (ICH OR 0.93 CI 0.85-1.00: sICH OR 0.95 CI 0.86-1.04), and patients with less severe stroke were more likely to have hemorrhage (ICH OR 1.06 CI 1.02-1.10; sICH OR 1.08 CI 1.03-1.13). IRR among the CT scan readers was moderate (k=0.504). Conclusions: ARWMC scores were not associated with post-tPA ICH in the elderly. Our analysis lends support for the use of tPA despite severity of white matter disease. ARWMC should not be used to assist in tPA decision-making in elderly patients via telestroke.

scholarly journals Regenerative Medicine Approaches for Age-Related Muscle Loss and Sarcopenia: A Mini-Review

Gerontology ◽  
2017 ◽  
Vol 63 (6) ◽  
pp. 580-589 ◽  
Author(s):  
Juan Diego Naranjo ◽  
Jenna L. Dziki ◽  
Stephen F. Badylak
Keyword(s):  
Regenerative Medicine ◽  
Treatment Options ◽  
The Elderly ◽  
Signaling Molecules ◽  
Current Treatment ◽  
Muscle Physiology ◽  
Age Related ◽  
Increased Risk ◽  
And Function ◽  
Age Related Changes

Sarcopenia is a complex and multifactorial disease that includes a decrease in the number, structure and physiology of muscle fibers, and age-related muscle mass loss, and is associated with loss of strength, increased frailty, and increased risk for fractures and falls. Treatment options are suboptimal and consist of exercise and nutrition as the cornerstone of therapy. Current treatment principles involve identification and modification of risk factors to prevent the disease, but these efforts are of limited value to the elderly individuals currently affected by sarcopenia. The development of new and effective therapies for sarcopenia is challenging. Potential therapies can target one or more of the proposed multiple etiologies such as the loss of regenerative capacity of muscle, age-related changes in the expression of signaling molecules such as growth hormone, IGF-1, myostatin, and other endocrine signaling molecules, and age-related changes in muscle physiology like denervation and mitochondrial dysfunction. The present paper reviews regenerative medicine strategies that seek to restore adequate skeletal muscle structure and function including exogenous delivery of cells and pharmacological therapies to induce myogenesis or reverse the physiologic changes that result in the disease. Approaches that modify the microenvironment to provide an environment conducive to reversal and mitigation of the disease represent a potential regenerative medicine approach that is discussed herein.

Low vitamin D status is associated with hearing loss in the elderly: a cross-sectional study

2020 ◽  
Author(s):  
Betsy Szeto ◽  
Chris Valentini ◽  
Anil K Lalwani
Keyword(s):  
Vitamin D ◽  
Hearing Loss ◽  
Low Frequency ◽  
The Elderly ◽  
Vitamin D Status ◽  
Total Calcium ◽  
Mineral Density ◽  
Cross Sectional ◽  
Age Related ◽  
Increased Risk

ABSTRACT Background The elderly are at increased risk of both hearing loss (HL) and osteoporosis. Bone mineral density (BMD) has been putatively linked to HL. However, the roles of serum calcium concentrations and vitamin D status have yet to be elucidated. Objectives The purpose of this study was to examine the relation between vitamin D status, parathyroid hormone (PTH), total calcium, BMD, and HL in a nationally representative sample of elderly adults. Methods Using the NHANES (2005–2010), audiometry and BMD data of 1123 participants aged ≥70 y were analyzed in a cross-sectional manner. HL was defined as pure tone averages &gt;25 dB HL at 500, 1000, and 2000 Hz (low frequency); 500, 1000, 2000, and 4000 Hz (speech frequency); and 3000, 4000, 6000, and 8000 Hz (high frequency) in either ear. Multivariable logistic regression was used to examine the relation between HL and total 25-hydroxyvitamin D [25(OH)D], PTH, total calcium, and BMD, adjusting for covariates. Results In multivariable analyses, total 25(OH)D &lt; 20 ng/mL was found to be associated with greater odds of low-frequency HL (OR: 2.02; 95% CI: 1.28, 3.19) and speech-frequency HL (OR: 1.96; 95% CI: 1.12, 3.44). A 1-unit decrease in femoral neck BMD (OR: 4.55; 95% CI: 1.28, 16.67) and a 1-unit decrease in total spine BMD (OR: 6.25; 95% CI: 1.33, 33.33) were found to be associated with greater odds of low-frequency HL. Serum PTH and total calcium were not found to be associated with HL. Conclusions In the elderly, low vitamin D status was associated with low-frequency and speech-frequency HL. Low vitamin D status may be a potential risk factor for age-related HL.

Optimizing Antiepileptic Drug Therapy in the Elderly

2005 ◽  
Vol 39 (11) ◽  
pp. 1852-1860 ◽  
Author(s):  
William R Garnett
Keyword(s):  
Drug Therapy ◽  
Elderly Patients ◽  
Antiepileptic Drug ◽  
Age Groups ◽  
The Elderly ◽  
Complex Partial Seizures ◽  
Medline Search ◽  
Age Related ◽  
Epilepsy In The Elderly ◽  
Clonic Seizures

OBJECTIVE To review and evaluate the medical literature concerning antiepileptic drug (AED) therapy in elderly patients. DATA SOURCES A MEDLINE search (1982–December 2004) was conducted. Bibliographies of the articles identified were also reviewed, and an Internet search engine was used to identify additional pertinent references. STUDY SELECTION AND DATA EXTRACTION Clinical studies and reviews were evaluated, and relevant information was included. DATA SYNTHESIS The elderly have the highest incidence of seizures among all age groups. Complex partial seizures are the most common, followed by primary generalized tonic–clonic seizures. An accurate diagnosis may prove difficult because of a low suspicion of epilepsy in the elderly and other diseases that may mimic seizures. Most AEDs are approved for treatment of elderly patients who have partial and tonic–clonic seizures. However, a number of age-related variables should be addressed when selecting an appropriate AED. Age-dependent differences in pharmacokinetics and pharmacodynamics of AEDs must be taken into account. Drug–drug interactions must be considered since elderly people often take multiple medications. The ultimate factor that often determines AED selection is tolerability. CONCLUSIONS Numerous factors must be considered in treating elderly patients for seizures, but maximizing the ability of patients to tolerate drug therapy is often the basis for AED selection. Special consideration should be made along several lines, including elderly patients’ cognitive functioning and their tendency to respond to lower AED concentrations.

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