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The authors examined whether the epsilon4 allele might be associated with dementia in Parkinson disease (PD), given that the dementia of PD shares neuroanatomic and neurochemical features with Alzheimer disease (AD) and that many recent studies have found a high prevalence of the epsilon4 allele of apolipoprotein E (ApoE) in AD. The authors examined patients with PD (n=125, 47 demented) and unrelated controls (n=93) using a short mental test. DNA was obtained from blood leukocytes. The relevant portion of the apolipoprotein E (ApoE) gene was amplified by polymerase chain reaction, and the epsilon4 allele was identified using a restriction enzyme. The frequency of the ApoE epsilon4 allele in demented patients with PD (14%) was not greater than that in nondemented patients (17%), whereas patients with PD as a whole showed a trend toward a higher epsilon4 allele frequency (16%) than age-matched controls (10%, p=0.07). The epsilon4 allele frequency in nondemented patients with PD was significantly higher than in controls (p=0.055). These results and the meta-analysis of four published reports fail to support the hypothesis that the epsilon4 allele is associated with dementia in PD.

APOE-e4 has been consistently found to be frequent in patients with senile dementia of the Alzheimer type (SDAT). Since forgetfulness may represent an early stage of dementia, APOE-e4 frequency can be expected to be high in such subjects, particularly in those who later develop dementia. We examined here the proportion of e4 alleles in patients with SDAT (n = 179), controls (n = 154) and subjects with age-related memory complaints (ARMC, n = 167); 16 of them developed dementia of Alzheimer type and three of them dementia of vascular type. We also evaluated the relative risk of dementia (of Alzheimer type) in ARMC subjects who are e4-carriers, using a Cox proportional hazards model. The APOE-e4 allele frequency was 27% in SDAT, 25% in ARMC patients who became demented, 15% in ARMC subjects who remained such after at least 1 year of follow-up, and 10% in controls. APOE-e4 allele was significantly more frequent in SDAT than in controls or than in stable ARMC (OR = 3.7 [2–6.3] and OR = 2.5 (1.5–4], respectively, p > 0.01). The risk of dementia in ARMC subjects carrying an e4 allele was three-fold that of those without (expβ = 3.1 [0.98–10], p = 0.05). Older age at onset of memory decline and lower minimental scores at initial visit were also associated with development of dementia in ARMC subjects (exp β = 1.1 [1.0–1.2], p = 0.05 and exp = 0.76 [0.6–0.9]), p = 0.008). In conclusion, the APOE-e4 allele was found to occur frequently in ARMC who subsequently develop dementia, therefore it can indicate a predisposition for dementia in such patients.

The development of therapies for Alzheimer's disease (AD) has focused on drugs designed to correct the loss of cholinergic function within the central nervous system. Quantitative EEG (qEEG) changes associated with AD consist of background slowing. One way to study the effects of cholinergic drugs may be through assessment of their qEEG effects. The aim of the current work was to evaluate the effect of long-term treatment with tetrahydroaminoacridine (THA) on qEEG in AD patients.

Background: The risk of developing dementia by elderly patients with only subjective memory complaints (SMC) is unclear. Our objective was to assess the prognosis of such patients regarding subsequent development of dementia.Methods: From 1992 to 1996, 211 consecutive patients (age 67.4±9.4 years, mean±SD) were diagnosed as having SMC. These patients were followed for 3 years or to the time they were diagnosed with dementia, whichever came first. A survival analysis was performed for occurrence of dementia within 3 years.Results: The duration of memory decline was shorter among patients who developed dementia than among those who did not (32.6 vs. 49.9 months, F=3.3, p=0.07). Patients who developed dementia tended to be older at the reported onset of memory decline (71 vs. 66.2 years, F=3.2, p=0.07). Lower risk of dementia was associated with higher cognitive performance at entry [odds ratio (OR)=0.74 (0.59–0.92)] and longer time from onset of memory decline to referral [OR=0.91 (0.85–0.98)].Conclusion: Subjects with SMC have an increased risk of developing dementia, particularly those with lower cognitive status at entry and with older age at onset of memory complaints, and shorter duration of their memory complaints.

The apolipoprotein E (APOE) epsilon 4 allele has been consistently found to be frequent in patients with progressive degenerative dementia of the Alzheimer type (DAT). Vascular dementia (VD) may occur as strokes superimposed on presymptomatic DAT, in which case APOE-epsilon 4 frequency should also be increased in VD. We have examined the distribution of APOE-epsilon 4 in patients with DAT (n = 176) or VD (n = 74) and controls (n = 133), and evaluated the risk of dementia associated with APOE-epsilon 4. APOE-epsilon 4 allele frequency was 27% in DAT patients, 21% in VD patients, and 11% in controls. The difference in the distribution of the epsilon 4 allele between DAT or VD patients and controls was statistically significant (chi(2) test, p < 0.05), with a 3.6- and 2.1-fold risk of dementia in DAT and VD patients carrying an epsilon 4 allele. The result that the APOE-epsilon 4 allele is more frequent in DAT patients than in controls, with VD patients falling in between, is consistent with the assumption that VD is a heterogeneous condition, with some patients having an underlying preclinical brain degeneration, in whom the dementia was precipitated by strokes.

Clinical trials for Alzheimer's disease take place in medical centers all over the world. Patients and caregivers have to decide whether or not to agree to participate in clinical trials. This study aimed to investigate the motivation that determines the caregivers' choice. Nineteen caregivers of demented patients who consented to participate in a clinical trial in our Memory Clinic and 10 caregivers who refused to participate were interviewed. The data were gathered by a self-report questionnaire covering various aspects of the caregivers' decision-making process. Among the reasons for agreeing to participate in the clinical trial were the respondents' belief that it would improve or help to maintain the patients' condition. Most of the respondents of both groups indicated that information regarding side effects and success probability was adequately provided in advance. The primary reason for refusal was the potential side effects of the drug. The implications of the findings are discussed.

Patients with Alzheimer’s disease (AD) suffer from decline of memory, which may be more pronounced for anterograde than retrograde events. The deficits refer mostly to biographical and public events (Lezak, 1995; Greene and Hodges, 1996). Nevertheless, it is likely that repetition of information may prevent forgetting. The historical importance of Prime Minister Ytzhak Rabin’s assassination in 1995 prompted us to ask whether such an event, which was repetitively covered by the media, is retained by demented patients.

The AF series compounds, AF102B and congeners of AF150(S), are functionally selective agonists for m1 muscarinic receptors (m1AChRs). This is shown in stable transfected CHO and PC12 cells (PC12M1) with m1m5AChRs and m1AChRs, respectively. AF102B and AF150(S) are partial agonists, but AF150, AF151, and AF151 (S) are full agonists in stimulating phosphoinositides hydrolysis or arachidonic acid release in these cells. Yet, all these compounds behave as antagonists when compared with carbachol in elevating cAMP levels. In PC12M1 cells, unlike carbachol, the AF series compounds induce only minimal to moderate neurite outgrowth. Yet, these agonists synergize strongly with NGF, which by itself mediates only a mild response. Stimulation of m1AChRs by AF102B, AF150(S) and AF151(S) in PC12M1 cells enhances secretion of beta/A4 amyloid precursor protein derivatives (APPs). The enhanced APPs secretion induced by AF102B is potentiated by NGF. AF102B also stimulates APPs secretion from rat cortical slices. Stimulation of m1AChR in PC12M1 cells with carbachol or AF102B decreases tau phosphorylation as indicated by specific tau-1 mAb and alkaline phosphatase treatment. Due to the above mentioned properties m1 agonists may be of unique value in delaying the progression of Alzheimer's disease (AD). The AF series compounds show a wide safety margin and improve memory and learning deficits in animal models for AD. There is a dearth of clinical reports on m1 agonists. These include studies on AF102B and xanomeline, another m1 selective agonist. We tested AF102B in escalating doses of 20, 40, 60 mg, tid, po, (each dose for 2 weeks) for a total of 10 weeks. This was a single-blind placebo-controlled, parallel-group study in patients with probable AD. AF102B was significantly effective at 40 and 60 mg, tid in the ADAS, ADAS-cognitive and ADAS-word recognition scales.

The apolipoprotein E (APOE) epsilon 4 allele has been consistently found to be frequent in patients with progressive degenerative dementia of the Alzheimer type (DAT). Vascular dementia (VD) may occur as strokes superimposed on presymptomatic DAT, in which case APOE-epsilon 4 frequency should also be increased in VD. We have examined the distribution of APOE-epsilon 4 in patients with DAT (n = 176) or VD (n = 74) and controls (n = 133), and evaluated the risk of dementia associated with APOE-epsilon 4. APOE-epsilon 4 allele frequency was 27% in DAT patients, 21% in VD patients, and 11% in controls. The difference in the distribution of the epsilon 4 allele between DAT or VD patients and controls was statistically significant (chi(2) test, p0.05), with a 3.6- and 2.1-fold risk of dementia in DAT and VD patients carrying an epsilon 4 allele. The result that the APOE-epsilon 4 allele is more frequent in DAT patients than in controls, with VD patients falling in between, is consistent with the assumption that VD is a heterogeneous condition, with some patients having an underlying preclinical brain degeneration, in whom the dementia was precipitated by strokes.