Table 1.

Summary of clinical studies of seizures and AD

Study	Study type	N	Age	Follow‐up	N (%) Szs	EEG	Seizure type	Treatment	Risk factors and relationship to dementia stage	Pathology	Methodological issues
Sjorgren et al. 1952 [20]	Retrospective autopsy study of patients with AD and Pick's disease	18	53.0 ± 5.0	n/a	4 (22%)	n/r	n/r	n/r	All during late stage of dementia	Yes	Small sample size, limited clinical information available, Sz diagnosis uncertain
Letemendia et al. 1958 [70]	Retrospective autopsy series of patients with AD and EEGs	17	31–60	n/a	7 (41%)	EEGs in all pts with Szs 3 (42%) had IEDs	n/r	n/r	n/r	Yes	Small sample size, early onset patients.
Sulkava et al. [7]	Cross‐sectional study of hospitalized AD patients at one center in Finland	71	35 AD onset before age 65	n/a	6 (8%)	All had 8 channel EEG IEDs not reported	n/r	n/r	n/r	No	Diagnosis of epilepsy not well characterized, EEG findings not described; not assessed for other potential causes of Sz
Hauser et al. 1986 [8]	Retrospective autopsy series of AD patients in Rochester, MN	83	n/r	n/a	8 (9.6%) 5/8 had epilepsy	n/r	“convulsive” Szs (other Sz types not assessed)	n/r	Mean latency to first Sz was 6.5 from dementia onset	Yes	Retrospective, criteria for Sz diagnosis unclear, assessed only convulsive Szs
Heyman et al. 1987 [27]	Prospective cohort study of early onset probable AD patients at a single center	92	62 (51–74)	1–6.8 yrs	13 (14%)	n/r	n/r	n/r	Szs occurred late in course of dementia	Yes for 14	Diagnosis of epilepsy not well characterized; EEG findings not described; limited pathological confirmation
Romanelli et al. 1990 [10]	Prospective case‐control study of patients with mild AD	44 (58 controls)	71.5 ± 4.9	90 months	7 (16%) (vs. 0 in control group)	EEG in 2 pts only; IEDs seen in both	All had “GTC” 2 (29%) pts noted to have focal features (Todd's)	PHT	All had advanced dementia at time of Sz	Yes for 3	EEG not performed; Sz diagnosis is clinical/historical, limited pathological confirmation
Risse et al. 1990 [9]	Prospective cohort study of hospitalized male suspected AD patients who had autopsy	28	51–83	n/a	14 (64%)	n/r	n/r	“most” patients treated	12 (86%) had Szs noted in last 1/2 of illness	Yes	EEG not noted, Sz diagnosis not specified, duration of follow‐up not stated, male only
Forstl et al. 1992 [21]	Prospective autopsy series	56	75.4 ± 7.4	n/a	6 (10%)	n/r	“generalized motor seizures” in all	n/r	Szs in late stage of disease	Yes. Patients with Szs had cell loss in parietal lobe and in parahippocampal gyrus but not in CA1	Limited details on Sz diagnosis; assessment via historical information, older onset group
McAreavey et al. 1992 [11]	Cross‐ sectional retrospective study of hospitalized patients with dementia in Scotland	208	58–94	n/a	19 (9.1%)	n/r	82 total Sz reported, 59 (72%) 2nd GTCs, 18 (22%) CPS, 5 (6%) unclassified	8 (42%) of pts with Szs on AEDs (PHT, CBZ, or PB)	Sz patients younger more impaired on CAPE information/orientation score, trend toward lower MMSE scores	No	Inpatients likely represent more severe disease type, no clear criteria for making AD diagnosis, ascertainment of epilepsy/Sz not clearly defined
Mendez et al. 1994 [12]	Retrospective autopsy series from a brain bank	446	64.1 ± 8.8 (Sz group) 67.0 ± 9.8 (no Sz group)	n/a	77 (17%)	52 (67%) total EEGs 39 (75%) with focal slowing; 15 (29%) with IEDs	69 (89%) GTC; 9 (11%) partial	65 (84%) were on AED	Younger age of onset of AD compared to age‐/sex‐matched non‐Sz AD patients; mod‐advanced AD;	Yes. No neuropath‐ological differences between pts with and without Szs	Not matched for AD severity at time of Sz (only age of onset/duration of illness). Sz ascertainment based on historical information, family questionnaire
Volicer et al. 1995 [13]	Cross‐sectional study of hospitalized patients with probable AD	75	70.6 ± 4.4	n/a	27 (36%)	No discussion of IEDs in patients who had EEGs (number not stated)	n/r	23 pts (85%) treated	Szs were associated with worsening in language function	Yes for 17 (63%)	No clear criteria for diagnosing epilepsy; variable disease severity at onset, incomplete pathological confirmation
Hesdorffer et al. 1996 [14]	Population‐based case‐control study in Rochester, MN, of patients >55 yrs with 1st unprovoked Sz; compared to 2 age‐matched controls without Szs at time of diagnosis	145	55–94	n/a	17 (11%) of patients with Sz had AD	n/r	6 (35%) AD pts partial onset Sz 11 (65%) AD pts generalized onset Sz	n/r	Szs occurred 3.3 (0.4–9.3) yrs from AD onset	No	Sz diagnosis based on historical data
Samson et al. 1996 [35]	Cross‐sectional population study of patients with probable early onset AD	198	36–64	n/a	13 (7%) at time of initial AD diagnosis; 94 (45%) over course of AD	n/r	n/r	n/r	Presence of myoclonus was associated with a 7.7 RR of having Szs.	No	Retrospective, Sz diagnosis made from chart only, criteria for epilepsy diagnosis is not clearly delineated
Lozsadi and Larner 2006 [16]	Retrospective cohort study, single outpatient dementia clinic with clinical AD diagnosis	177	49–84	n/a	12 (6.8%) total; half had Szs felt to be temporally related to AD onset	n/r	All 6 (100%) with epilepsy after AD onset had CPS, 1 (17%) with 2nd GTC	n/r	n/r	No	Clinical diagnosis, retrospective, small size, criteria for epilepsy diagnosis is not clearly delineated
Amatniek et al. 2006 [15]	Prospective cohort study of mild probable AD patients from 3 centers	233	n/r	5.99 yrs (0–8.95)	12 (7.75%).	135 (58%) had EEG Focal IEDs in all Sz subset (9 Sz pts had EEGs)	n/r	n/r	Sz more common in younger, African American, more severely demented	No	EEGs not performed on all patients. Sz diagnosis by history, chart review, clinical impression; incomplete information on many patients; no age‐matched control cohort (Sz rates in controls estimated from literature)
Scarmeas et al. 2009 [18]	Prospective cohort study of mild probable AD from 3 centers	453	74.4 ± 8.9 yrs	3.9 yrs	7 (1.5%); 3 (0.7%) with epilepsy	21 pts (5%) had EEGs; 3 of these (16%) had epileptiform activity	GTC in 6 (86%)	Only 4 treated	Sz more common in younger patients	Yes for 15	EEGs not performed on all patients. Sz diagnosis made by review of chart—patients; incomplete information on many patients. No age‐matched control cohort (Sz rates in controls estimated from literature)
Rao et al. 2009 [17]	Retrospective cohort study of dementia and MCI outpatients in single center AD registry	1738	50–100	n/a	61 (3.6%) had epilepsy (sufficient records on 31 [1.7%])	29 (72%) had EEGs 15 (51%) had IEDs	44 (72%) had CPS 22 (36%) had probable remote symptomatic cause for their epilepsy	AEDs used: PHT, VPA, CBZ, GBP, PB, CLZ; 79%“excellent” response	n/r	No	Retrospective, included MCI and patients with remote symptomatic causes of epilepsy predating onset of cognitive impairment. Not controlled for disease severity. Limited, incomplete clinical information
Bernardi et al. 2010 [19]	Retrospective cohort study of probable AD patients at single center	145	51–91	n/a	14 (9.7%) with Sz; 10 (6.9%) had epilepsy	Incomplete EEGs in non‐Szs cohort; in Sz cohort 37.5% had IEDs	13 (93%) had CPS with secondary generalization	n/r	Nonsignificant trend for Sz occurring in more severe dementia	No	Retrospective, Sz diagnosis based on chart review

n/a, not applicable; n/r, not reported; AD, Alzheimer's disease; IED, interictal discharges; CPS, complex partial seizure; GTC, generalized tonic‐clonic seizure; MCI, mild cognitive impairment; MID, multi‐infarct dementia; 2nd GTC, secondarily generalized tonic‐clonic seizure; Sz, seizure; PHT, phenytoin; CBZ, carbamazepine; CLZ, clonazepam; GPB, gabapentin; VPA, valproic acid; PB, phenobarbital.