Adapting a United States cancer education programme for South Africa: A participatory, culturally tailored approach using Card's Seven-Step adaptation framework.

Epilepsy is a common neurologic disorder displaying a characteristic U-shaped distribution with incidence peaks in early childhood and in the elderly. In older adults, the leading causes of epilepsy are mainly cerebrovascular disease and brain tumors; however, a considerable proportion of cases, ranging from 33% to 53%, occur without an identifiable etiology. These cases are collectively referred to as late-onset unexplained epilepsy (LOUE), among which temporal lobe epilepsy (LO-TLE) represents one of the most frequent clinical subtypes. LOUE and Alzheimer disease (AD) are increasingly recognized as interrelated conditions sharing common pathophysiologic mechanisms. Patients with mild cognitive impairment (MCI) or AD have an increased risk of seizures, with lifetime prevalence ranging from 20% to 64%. Multiple studies report that individuals with LOUE have a higher risk of developing MCI or dementia than age-matched individuals without epilepsy. Reduced CSF β-amyloid (Aβ) levels and increased phosphorylated tau (p-tau) concentrations have been reported in LOUE, with up to one-third of patients displaying an AD-like CSF biomarker profile. These alterations suggested the hypothesis that in a subset of patients, LOUE may represent an early manifestation of AD-related neurodegeneration. However, LOUE is increasingly recognized as a clinically and biologically heterogeneous condition rather than a single-disease entity. Evidence indicates that LOUE includes forms with and without neurodegenerative biomarker abnormalities. This heterogeneity mirrors the clinical variability in LOUE and highlights the need for more refined phenotypic characterization. In our previous work, we showed that LO-TLE patients with normal CSF AD biomarkers display preserved cortical and subcortical morphology, clearly distinguishing them from MCI due to AD (MCI-AD). These findings suggest that LO-TLE itself may not be an intrinsic risk factor for AD-related neurodegeneration and underscore the importance of integrating clinical phenotyping, brain morphometry, and CSF neurodegenerative biomarkers to accurately characterize this population. Building on these results and the same cohort, this study substantially extends our previous work by providing a comprehensive neuropsychological characterization and by expanding the CSF biomarker assessment with neurofilament light chain (NfL) and the phosphorylated-to-total tau (p/t-tau) ratio, biomarkers not previously investigated in the LO-TLE population. Accordingly, we addressed the following questions: (1) do LOUE patients with normal CSF AD-related biomarkers show cognitive impairment compared with healthy controls (HCs)? (2) Does their cognitive profile differ from patients with MCI-AD? (3) Can their biological profiles be further refined through the consideration of these additional CSF biomarkers? We hypothesized that patients with LO-TLE present cognitive impairments despite normal AD-related CSF biomarkers and that their biomarker profile may point toward a neurobiological mechanism independent of the AD process. This observational study included 2 groups of patients, LO-TLE and MCI-AD, retrospectively selected from a previously published cohort. Patients with LO-TLE were evaluated at the Epilepsy Center at the Modena Academic Hospital (Azienda Ospedaliero-Universitaria di Modena, Italy). Patients with MCI-AD were recruited through the Cognitive Neurology Clinic at the same institution. In both cases, patients were referred by general practitioners, neurologists, or other specialists within the regional health care network for diagnostic evaluation and management. For patients with LO-TLE, inclusion criteria were (1) epilepsy onset after 50 years, consistent with epidemiologic data; (2) diagnosis of TLE according to the International League Against Epilepsy (ILAE) criteria confirmed by expert epileptologists (S.S., G.G., M.P., N.O., S.M., and A.E.V.); (3) evidence of unilateral or bilateral temporal epileptiform activity (ictal and/or interictal) on long-term video-EEG monitoring; (4) availability of high-resolution 3D T1-weighted (3D-T1) and 3-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences; and (5) normal CSF AD biomarkers, according to our laboratory-specific established cutoffs: Aβ >600 pg/mL, Aβ ratio >0.069, total tau (t-tau) <400 pg/mL, and phosphorylated tau 181 (p-tau) <56.5 pg/mL. Patients with a history of other significant neurologic or psychiatric disorders, a preexisting diagnosis of dementia, use of acetylcholinesterase inhibitors, or a Mini-Mental State Examination (MMSE) raw score lower than 26 were excluded. 3D-FLAIR images were inspected for white matter disease load (i.e., Fazekas score) by 2 expert neuroradiologists (M.M. and M.G.), with scores defined as follows: (0) none or a single lesion, (1) multiple punctate lesions, (2) beginning confluence, and (3) large confluent lesions. Inclusion criteria for the MCI-AD group were (1) diagnosis accordi