Dementias are a diverse group of disorders that erode complex brain functions required to live independently. While Alzheimer’s disease, the most common form of dementia, causes an abnormal decline in memory and other cognitive functions, other dementias more typically cause inappropriate behaviors, vivid hallucinations, or movement abnormalities. While some dementias, for example, the dementia caused by untreated HIV infection, can be reversed with rationally designed therapeutic interventions, aging-related neurodegenerative dementias such as Alzheimer’s disease, frontotemporal dementia and Lewy body dementia still remain irreversible. However, clinical trials suggest that even the progression of Alzheimer’s disease can be slowed with appropriate treatments, which gives us great hope and optimism in our research.

Epilepsy can emerge at different life stages and manifest in many different ways. Its symptoms range from dramatic seizures featuring generalized convulsions with loss of consciousness and incontinence to much more subtle changes in brain rhythms during sleep that go unnoticed by the patients and their families. Epileptic activity is typically caused by processes that result in an imbalance between excitation and inhibition in the brain such as overactivation of excitatory neurons or impairments of inhibitory neurons. Epileptic activity can interfere with normal brain functions, cause neurodegeneration, and occur by itself or in association with other brain disorders. For example, together with clinical collaborators, we showed that a substantial proportion of patients with Alzheimer’s disease have non-convulsive epileptiform activity, especially during sleep, and that the presence of this activity predicts a faster cognitive decline. These findings have important mechanistic and therapeutic implications (see Disease Mechanisms and Translation sections for details).

The many symptoms of autism include characteristic alterations in social interactions and communication as well as repetitive movements and behaviors. Our focus in this area is on severe autism spectrum disorders that cause major disability, lack effective treatments, and are often associated with intellectual disability, epilepsy, or both. These conditions can be caused by genetic changes that overactivate biochemical pathways that regulate brain growth and the excitation/inhibition balance of neuronal networks. These pathways offer promising entry points for therapeutic interventions that we are eager to explore and leverage.

Neurodevelopmental disorders that cause autism or epilepsy also often result in intellectual disability, an early-life counterpart to the loss of cognitive abilities caused by aging-related dementias. Both types of disorders not only impair cognitive functions, but also lead to behavioral alterations that are difficult to manage and can cause a great deal of stress to patients and caretakers alike.