Seizures in Alzheimer’s disease Vikas Dhikav, MBBS (Rohtak), MD (3-years AIIMS) , PhD (Neurology, PGIMER Delhi), Fellowship Clinical Neuropsychopharmacology, Director, Memory Clinic Delhi, www.memoryclinicdelhi.com Seizures in Alzheimer’s disease

Alzheimer’s disease Most common cause of dementia. Affects around 1 Crore people in India! PrecursorMild Cognitive Impairment (MCI)

Risk AD  upto 10-fold increased risk of developing seizures. Seziurescommon in AD   Hesdorffer DC et al., Neurology. 1996;46:727–730.

Incidence AD and other neurode-generative conditions presumed etiology 10% of new onset epilepsy in patients older than 65 years. Hauser WA, Annegers JF, Kurland LT.  Epilepsia. 1993;34:453–468.

Prevalence Lifetime prevalence seizures with AD1.5 to 64 percent Hauser HA, Neurology, 1986

Why AD has seizures? AD risk for late-onset seizures and neuronal network abnormalities.  Born, Neuroscience, 2014

Sporadic Vs Familial More common in sporadic form of AD. 

Common problem!  Nonconvulsive network abnormalities, seizures and other electroencephalographic abnormalities, more commonly found in patients than previously thought.  Hauser HA, Neurology, 1986

Genetics More common imutations in PSEN1, PSEN2, or APP, as well as with APP duplication Born, Neuroscience, 2014

Pathophysiology The amyloid-β possible link AD and seizures. 

Seizures worsen AD Seizures contribute to cognitive impairments characteristic of AD, such as amnestic wandering. 

Experimental evidence Antiepileptic drugs rescue cognitive deficits in AD mouse models and human patients.

Epilepsy and AD Epilepsy Alzheimer’s disease Potential research area

Potential Rx targets Better Treatment Alzheimer’s disease Neuronal hyperexcitability Neuronal abnormalities Nikolas et al., Arch Neurol. 2009; 66(8): 992–997.

World experience Occur in about 10%, 10 times more common than reference population. Can occur anytime. Generalized seizures occur early. Myoclonuslate seziures. Hauser HA, Neurology, 1986

Indian experience Category Sample size (n) =171 Age (Years) Sex MMSE AD 75 75±5 M:F=60:15 18±5 MCI 96 67±7 M:F=76:20 24±2

Proportion of seizures in AD/MCI

Indian experience… Category Seizures Duration of illness (Years) Drug Treatment AD GTCS (7), Partial (2) 3.6±3 Valproate/Levitiracetam MCI GTCS (4), Partial (2) 2.5 ±2

Epilepsy and AD overlap Do epilepsy and AD share pathophysiology? Dionysios Pandis, Epilepsy Curr. 2012; 12(5): 184–187.

Manifestations The diagnosis of seizures in AD not easyunderestimation. “Funny” or “unusual” behaviors of demented patients seizuresoverestimation of seizure rates.

Seizure types Generalizedmost common Partial seizures

Predictors Seizure prevalence increase with AD duration. Onset of seizures later stages of the disease.

Be aware!  Patients with dementia nonepileptic episodes of inattention or confusion as well as syncope or near-syncope. Nikolas et al., Arch Neurol. 2009; 66(8): 992–997.

Treatment Choice of AEDs empirical based on side effect profiles.