Table 1.
| Study | Study Type | N | Age | Follow up |
N (%) szs | EEG | Seizure Type |
Treat- ment |
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, seizure diagnosis uncertain |
| Letemendia et al. 1958 [64] | 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 in one center in Finland |
71 | 35 AD onset before age 65 |
n/a | 6 (8%) | All had 8 chan 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 | “convulsiv e” 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 [22] |
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 / 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 | n/r | “generali zed motor seizures” in all |
Szs in late stage of disease |
Yes. Patients with szs had cell loss in parietal lobe and in parahippoc ampal gyrus but not in CA1 |
Limited details on seizure diagnosis; assessment via historical information, older onset group |
| McAreavey et al. 1992 [11] |
Cross- sectional retrospective study o f 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%) unclassifie d |
8(42%) of pts with szs on AEDs (PHT, CBZ or PB) |
Sz patients younger more impaired on CAPE information/orientatio n score, trend towards 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 lEDs |
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 lEDs 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 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 (3 5%) AD pts partial onset sz 11 (65%) AD pts generalize d 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 [37] |
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, s z 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%) nd with 2 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 symptom atic cause for their epilepsy |
AEDs used: PHT, VPA, CBZ, GBP, PB, CLZ; 79% “excel lent” 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 generaliza tion |
n/r | Non-significant 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;