For nearly 20 years, the prevalent view has been that women who carry copies of the ε4 allele of the apolipoprotein E (APOE) gene have a greater risk of developing Alzheimer disease (AD) than men with the same number of copies.¹ The ε4 allele is the main genetic risk factor for late-onset Alzheimer disease (AD),² and sex-based differences in AD risk have important implications for treatment trials, diagnostics, and therapeutics.³ Additionally, the sex-dependent relationship between APOE and mild cognitive impairment (MCI), which is often a transitional phase from cognitively normal (NL) aging to dementia,⁴ is unclear. Studies are in general agreement that the APOE ε4 allele is a risk factor for developing MCI,^5-11 but there is controversy as to whether it increases^10,12-14 or does not increase^9,11,15,16 the risks of transitioning from MCI to AD or dementia. The 3 most common alleles of the APOE gene are ε2, ε3, and ε4; whereas carrying the ε4 allele increases one’s risk of developing AD, the ε2 allele conversely has a putative protective effect that is associated with longevity and a lower AD risk.¹⁷

DEPRESSION AND depression symptoms are common in persons with Alzheimer disease (AD).^1-8 When depression symptoms occur just before the development of AD, they may be early symptoms of the dementing process.^9-12 What remains unclear is whether depression occurring many years before the onset of cognitive decline is somehow a risk factor for the future development of AD.

Depression may be associated with an increased risk for dementia, although results from population-based samples have been inconsistent. We examined the association between depressive symptoms and incident dementia over a 17-year follow-up period. In 949 Framingham original cohort participants (63.6% women, mean age = 79), depressive symptoms were assessed at baseline (1990-1994) using the 60-point Center for Epidemiologic Studies Depression Scale (CES-D). A cutpoint of > or = 16 was used to define depression, which was present in 13.2% of the sample. Cox proportional hazards models adjusting for age, sex, education, homocysteine, and APOE epsilon4 examined the association between baseline depressive symptoms and the risk of dementia and Alzheimer disease (AD). During the 17-year follow-up period, 164 participants developed dementia; 136 of these cases were AD. A total of 21.6% of participants who were depressed at baseline developed dementia compared with 16.6% of those who were not depressed. Depressed participants (CES-D >/=16) had more than a 50% increased risk for dementia (hazard ratio [HR] 1.72, 95% confidence interval [CI] 1.04-2.84, p = 0.035) and AD (HR 1.76, 95% CI 1.03-3.01, p = 0.039). Results were similar when we included subjects taking antidepressant medications as depressed. For each 10-point increase on the CES-D, there was significant increase in the risk of dementia (HR 1.46, 95% CI 1.18-1.79, p < 0.001) and AD (HR 1.39, 95% CI 1.11-1.75, p = 0.005). Results were similar when we excluded persons with possible mild cognitive impairment. Depression is associated with an increased risk of dementia and AD in older men and women over 17 years of follow-up.

Objectives: It has been suggested in some studies that head injury is a risk factor for AD, and that this risk is heightened among carriers of the APOE-ε4 allele. We examined the effects of head injury and APOE genotype on AD risk in a large family study. Subjects: A total of 2,233 probands who met criteria for probable or definite AD and their 14,668 first-degree family members (4,465 parents, 7,694 siblings, and 2,509 spouses) were ascertained at 13 centers in the United States, Canada, and Germany participating in the MIRAGE (Multi-Institutional Research in Alzheimer Genetic Epidemiology) project. Information on head injury was collected by interview of multiple informants and review of medical records. Nondemented relatives and spouses served as control subjects for this study. Methods: Odds of AD for head trauma with or without loss of consciousness were computed by comparing probands with unaffected spouses using conditional logistic regression analysis. To account for the unique biologic relationship between probands and their parents and siblings, odds of AD were computed using a generalized estimating equation (GEE) Poisson regression approach. GEE logistic regression was used to examine the joint effects of APOE genotype and head injury on the odds of AD in probands and a control group comprised of unaffected siblings and spouses. Results: Comparison of probands with their unaffected spouses yielded odds ratios for AD of 9.9 (95% CI, 6.5 to 15.1) for head injury with loss of consciousness and 3.1 (2.3 to 4.0) for head injury without loss of consciousness. The corresponding odds derived from the comparison of probands with their parents and sibs were 4.0 (2.9 to 5.5) for head injury with loss of consciousness and 2.0 (1.5 to 2.7) for head injury without loss of consciousness. Head injury without loss of consciousness did not significantly increase the risk of AD in spouses (OR = 1.3; 95% CI, 0.4 to 4.1). The joint effects of head injury and APOE genotype were evaluated in a subsample of 942 probands and 327 controls (spouses and siblings). Head injury increased the odds of AD to a greater extent among those lacking ε4 (OR = 3.3) than among ε4 heterozygotes (OR = 1.8) or homozygotes (OR = 1.3). Conclusion: Head injury is a risk factor for AD. The magnitude of the risk is proportional to severity and heightened among first-degree relatives of AD patients. The influence of head injury on the risk of AD appears to be greater among persons lacking APOE-ε4 compared with those having one or two ε4 alleles, suggesting that these risk factors may have a common biologic underpinning.

There has been marked expansion in the literature and practice of pediatric sleep medicine; however, no recent evidence-based practice parameters have been reported. These practice parameters are the first of 2 papers that assess indications for polysomnography in children. This paper addresses indications for polysomnography in children with suspected sleep related breathing disorders. These recommendations were reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine A systematic review of the literature was performed, and the American Academy of Neurology grading system was used to assess the quality of evidence. Polysomnography in children should be performed and interpreted in accordance with the recommendations of the AASM Manual for the Scoring of Sleep and Associated Events. (Standard) Polysomnography is indicated when the clinical assessment suggests the diagnosis of obstructive sleep apnea syndrome (OSAS) in children. (Standard) Children with mild OSAS preoperatively should have clinical evaluation following adenotonsillectomy to assess for residual symptoms. If there are residual symptoms of OSAS, polysomnography should be performed. (Standard) Polysomnography is indicated following adenotonsillectomy to assess for residual OSAS in children with preoperative evidence for moderate to severe OSAS, obesity, craniofacial anomalies that obstruct the upper airway, and neurologic disorders (e.g., Down syndrome, Prader-Willi syndrome, and myelomeningocele). (Standard) Polysomnography is indicated for positive airway pressure (PAP) titration in children with obstructive sleep apnea syndrome. (Standard) Polysomnography is indicated when the clinical assessment suggests the diagnosis of congenital central alveolar hypoventilation syndrome or sleep related hypoventilation due to neuromuscular disorders or chest wall deformities. It is indicated in selected cases of primary sleep apnea of infancy. (Guideline) Polysomnography is indicated when there is clinical evidence of a sleep related breathing disorder in infants who have experienced an apparent life-threatening event (ALTE). (Guideline) Polysomnography is indicated in children being considered for adenotonsillectomy to treat obstructive sleep apnea syndrome. (Guideline) Follow-up PSG in children on chronic PAP support is indicated to determine whether pressure requirements have changed as a result of the child's growth and development, if symptoms recur while on PAP, or if additional or alternate treatment is instituted. (Guideline) Polysomnography is indicated after treatment of children for OSAS with rapid maxillary expansion to assess for the level of residual disease and to determine whether additional treatment is necessary. (Option) Children with OSAS treated with an oral appliance should have clinical follow-up and polysomnography to assess response to treatment. (Option) Polysomnography is indicated for noninvasive positive pressure ventilation (NIPPV) titration in children with other sleep related breathing disorders. (Option) Children treated with mechanical ventilation may benefit from periodic evaluation with polysomnography to adjust ventilator settings. (Option) Children treated with tracheostomy for sleep related breathing disorders benefit from polysomnography as part of the evaluation prior to decannulation. These children should be followed clinically after decannulation to assess for recurrence of symptoms of sleep related breathing disorders. (Option) Polysomnography is indicated in the following respiratory disorders only if there is a clinical suspicion for an accompanying sleep related breathing disorder: chronic asthma, cystic fibrosis, pulmonary hypertension, bronchopulmonary dysplasia, or chest wall abnormality such as kyphoscoliosis. (Option) Nap (abbreviated) polysomnography is not recommended for the evaluation of obstructive sleep apnea syndrome in children. (Option) Children considered for treatment with supplemental oxygen do not routinely require polysomnography for management of oxygen therapy. (Option) Current evidence in the field of pediatric sleep medicine indicates that PSG has clinical utility in the diagnosis and management of sleep related breathing disorders. The accurate diagnosis of SRBD in the pediatric population is best accomplished by integration of polysomnographic findings with clinical evaluation.

Dementia is increasingly recognized as a life-course illness wherein a variety of lifestyle choices interact with genetic, vascular, and other risk factors to affect risk of disease.¹ Given the rapid aging of developed and developing societies, it is projected that the prevalence of dementia will dramatically increase during the next 5 decades.² Therefore, it is a public health priority to explore pathophysiological pathways underlying the development of dementia and its most common cause, Alzheimer disease (AD).