Alzheimer's disease and epilepsy: shared neuropathology guides current and future treatment strategies.

Epilepsy is a cause of profound disability in patients with Alzheimer's disease (AD). The risk of being diagnosed with AD increases the risk for epilepsy, and in parallel, a history of epilepsy increases the likelihood of the development of AD. This bi-directional relationship may be due to underlying shared pathophysiologic hallmarks, including decreased cerebrospinal fluid amyloid beta 42 (Aß42), increased hyperphosphorylated tau protein, and hippocampal hyperexcitability. Additionally, there are practical treatment considerations in patients with co-morbid AD and epilepsy-namely, there is a higher risk of seizures associated with medications commonly prescribed for Alzheimer's disease patients, including antidepressants and antipsychotics such as trazodone, serotonin norepinephrine reuptake inhibitors (SNRIs), and first-generation neuroleptics. Anti-amyloid antibodies like aducanumab and lecanemab present new and unique considerations in patients with co-morbid AD and epilepsy given the risk of seizures associated with amyloid-related imaging abnormalities (ARIA) seen with this drug class. Finally, we identify and detail five active studies, including two clinical trials of levetiracetam in the respective treatment of cognition and neuropsychiatric features of AD, a study characterizing the prevalence of epilepsy in AD via prolonged EEG monitoring, a study characterizing AD biomarkers in late-onset epilepsy, and a study evaluating hyperexcitability in AD. These ongoing trials may guide future clinical decision-making and the development of novel therapeutics.

Lewy Body Dementia: An Overview of Promising Therapeutics.

PURPOSE OF REVIEW: Lewy body dementia (LBD) encompasses dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). This article will emphasize potential disease-modifying therapies as well as investigative symptomatic treatments for non-motor symptoms including cognitive impairment and psychosis that can present a tremendous burden to patients with LBD and their caregivers. RECENT FINDINGS: We review 11 prospective disease-modifying therapies (DMT) including four with phase 2 data (neflamapimod, nilotinib, bosutinib, and E2027); four with some limited data in symptomatic populations including phase 1, open-label, registry, or cohort data (vodabatinib, ambroxol, clenbuterol, and terazosin); and three with phase 1 data in healthy populations (Anle138b, fosgonimeton, and CT1812). We also appraise four symptomatic therapies for cognitive impairment, but due to safety and efficacy concerns, only NYX-458 remains under active investigation. Of symptomatic therapies for psychosis recently investigated, pimavanserin shows promise in LBD, but studies of nelotanserin have been suspended. Although the discovery of novel symptomatic and disease-modifying therapeutics remains a significant challenge, recently published and upcoming trials signify promising strides toward that aim.