Risk Of Alzheimer's Disease In Patients Research Articles

Association between migraine and Alzheimer's disease: a nationwide cohort study.

Migraine is a common chronic neurological disease characterized by pulsating headaches, photophobia, phonophobia, nausea, and vomiting. The prevalence of dementia in individuals aged over 65 years in Korea is more than 10%, and Alzheimer's disease (AD) dementia accounts for most cases. Although these two neurological diseases account for a large portion of the medical burden in Korea, few studies have examined the relationship between the two diseases. Therefore, this study investigated the incidence and risk of AD in patients with migraines. We retrospectively collected nationwide data from a national health insurance claims database governed by Korea's National Health Insurance Service. Among Koreans in the 2009 record, patients with migraine were identified according to the International Classification of Diseases, 10th revision (ICD-10) code G43. First, we screened the database for participants aged over 40 years. Individuals diagnosed with migraine at least twice over more than 3 months in a year were considered to have chronic migraine in this study. Further, all participants with an AD diagnosis (ICD-10 code: Alzheimer's disease F00, G30) were investigated for AD dementia development. The primary endpoint was AD development. The overall incidence of AD dementia was higher in individuals with a history of migraine than in those with no migraine history (8.0 per 1,000 person-years vs. 4.1 per 1,000 person-years). The risk of AD dementia was higher in individuals diagnosed with migraine (hazard ratio = 1.37 [95% confidence interval, 1.35-1.39]) than in the control group after adjustments for age and sex. Individuals with chronic migraine had a higher incidence of AD dementia than those with episodic migraine. Younger age (<65 years old) was associated with an increased risk of AD dementia compared to older age (≥65 years old). Higher body mass index (BMI) (≥25 kg/m2) was also associated with an increased risk of AD dementia compared to lower BMI (<25 kg/m2) (p < 0.001). Our results suggest that individuals with a migraine history are more susceptible to AD than those without a migraine history. Additionally, these associations were more significant in younger and obese individuals with migraine than in individuals without migraine.

Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS.

Alzheimer disease (AD) may develop after the onset of type 2 diabetes mellitus (T2DM), and the risk of AD may depend on the antidiabetic drug administered. We compared the risk of AD among 66 085 patients (≥ 65 years) with T2DM (1250 having concomitant AD) who had been administered antidiabetic drug monotherapy for T2DM who had voluntarily reported themselves in the Food and Drug Administration Adverse Event Reporting System. The risk of AD from the use of different antidiabetic drug monotherapies compared to that of metformin monotherapy was assessed by logistic regression. Rosiglitazone (adjusted reporting odds ratio [aROR] = 0.11; 95% confidence interval [CI]: 0.07-0.17; P < .001), exenatide (aROR = 0.22; 95% CI: 0.11-0.37; P < .001), liraglutide (aROR = 0.36; 95% CI: 0.19-0.62; P < .001), dulaglutide (aROR = 0.39; 95% CI: 0.17-0.77; P = .014), and sitagliptin (aROR = 0.75; 95% CI: 0.60-0.93; P = .011) were found to have a significantly lower associated risk of AD than that of metformin. Therefore, the administration of glucagon-like peptide 1 receptor agonists and rosiglitazone may reduce the risk of AD in patients with T2DM.

The APOE Genotype in Idiopathic Normal Pressure Hydrocephalus.

IntroductionAmyloid plaque has been reported in brain biopsies from patients with idiopathic normal-pressure hydrocephalus (iNPH) and proposed as a significant feature of the pathophysiology. Presence of the apolipoprotein E ε4 (APOE ε4) allele is associated with increased risk of Alzheimer’s disease (AD).AimsTo compare the distribution of APOE genotype in iNPH patients with an age-matched population-based control group and with Alzheimer’s disease (AD) patients.MethodsAPOE genotype frequencies were determined in 77 iNPH patients (50 men and 27 women, mean age 71.7 years) diagnosed with iNPH, a sample of 691 AD patients and 638 age-matched population controls (299 men and 339 women) from the INTERGENE cohort.ResultsThe APOE distribution did not differ significantly between the iNPH patients and the control population. The per e4-allele odds-ratio (OR) of iNPH was given by OR = 0.90, 95% confidence interval (CI) = (0.50, 1.60) that was considerably smaller than the per-allele OR of AD, OR = 5.34 (4.10, 7.00).ConclusionThe results suggest that the APOE-related risk of AD in patients with iNPH is not higher than in the general population.

Predictive Utility of Apolipoprotein E Genotype for Alzheimer Disease in Outpatients With Mild Cognitive Impairment

In cognitively impaired patients without dementia, the utility of apolipoprotein E (APOE) genotyping is unclear. To evaluate the predictive utility of the APOE epsilon4 genotype for conversion to probable Alzheimer disease (AD). Naturalistic, longitudinal study. Memory disorders outpatient clinic. A total of 136 patients with memory complaints were determined to have mild cognitive impairment and were evaluated every 6 months. Fifty-seven age- and sex-matched healthy controls were evaluated annually. Primary outcome measures included conversion to AD. Secondary outcome measures included change over time in Mini-Mental State Examination (MMSE) score and Selective Reminding Test (SRT) delayed recall score. The APOE epsilon4 allele was present in 25% of patients and 21% of healthy controls. During a mean +/- SD follow-up of 35.2 +/- 24.3 months, 35 of 136 patients converted to AD. APOE epsilon4 carrier status did not differ between converters (31%) and nonconverters to AD (23%, P = .3) and did not affect the time trend in MMSE or SRT scores in the entire sample. Four of 5 APOE epsilon4 homozygotes converted to AD compared with 7 of 29 heterozygotes (P = .02). In a Cox proportional hazards model stratified by age quartiles, after controlling for sex, education, MMSE score, and SRT delayed recall score, APOE epsilon4 increased the risk of AD in patients 70 to 85 years old (n = 57; risk ratio, 2.77; 95% confidence interval, 1.1-7.3; P = .03) but not in patients 55 to 69 years old (n = 79; P = .7). APOE epsilon4 carrier status was associated with conversion to AD in older outpatients after controlling for known demographic and clinical risk factors, and APOE epsilon4 homozygosity was associated with increased risk of conversion to AD. However, APOE epsilon4 carrier status by itself did not predict cognitive decline or conversion to AD, indicating that APOE genotyping in patients with mild cognitive impairment may have limited clinical applicability for prediction of outcome.

Alzheimer's disease and inflammation: a review of cellular and therapeutic mechanisms.

1. Of the neurodegenerative diseases that cause dementia, Alzheimer's disease (AD) is the most common. Three major pathologies characterize the disease: senile plaques, neurofibrillary tangles and inflammation. We review the literature on events contributing to the inflammation and the treatments thought to target this pathology. 2. The senile plaques of AD consist primarily of complexes of the beta-amyloid protein. This protein is central to the pathogenesis of the disease. 3. Inflammatory microglia are consistently associated with senile plaques in AD, although the classic inflammatory response (immunoglobulin and leucocyte infiltration) is absent. beta-Amyloid fragments appear to mediate such inflammatory mechanisms by activating the complement pathway in a similar fashion to immunoglobulin. 4. Epidemiological studies have identified a reduced risk of AD in patients with arthritis and in leprosy patients treated with anti-inflammatory drugs. Longitudinal studies have shown that the consumption of anti-inflammatory medications reduces the risk of AD only in younger patients (< 75 years). 5. There is a considerable body of in vitro evidence indicating that the inflammatory response of microglial cells is reduced by non-steroidal anti-inflammatory drugs (NSAID). However, no published data are available concerning the effects of these medications on brain pathology in AD. 6. Cyclo-oxygenase 2 enzyme is constitutively expressed in neurons and is up-regulated in degenerative brain regions in AD. Non-steroidal anti-inflammatory drugs may reduce this expression. 7. Platelets are a source of beta-amyloid and increased platelet activation and increased circulating beta-amyloid have been identified in AD. Anti-platelet medication (including NSAID) would prevent such activation and its potentially harmful consequences. 8. Increased levels of luminal beta-amyloid permeabilizes the blood-brain barrier (BBB) and increases vasoconstriction of arterial vessels, paralleling the alterations observed with infection and inflammation. Cerebral amyloidosis is highly prevalent in AD, compromising the BBB and vasoactivity. Anti-inflammatory medications may alleviate these problems.