An understanding of these epidemiological trends is essential to guide decision making in medicine and public health.2,3 E Ray Dorsey, Alexis Elbaz, and colleagues from the GBD 2016 Parkinson's ...Disease Collaborators4 now report in The Lancet Neurology an extensive summary of indirectly estimated changes in global prevalence, disability, and death rates related to Parkinson's disease between 1990 and 2016.4 The authors did a series of analyses, projections, and extrapolations using the data and methods of the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study.5 Despite the limited number of high-quality data sources for large geographical regions, and the broad and complex assumptions made in the GBD analyses, the results are of public-health interest. For studies based on registries or medical records, there might also have been increased recognition and coding of Parkinson's disease in routine medical care. Because prevalence reflects both the incidence and the duration of the disease, a central question is whether the risk or incidence of Parkinson's disease has increased in the past three decades. Some data point to an increase in incidence in some high-income countries.3,6,7 However, some studies did not confirm the increase, or reported a decrease.8 It is possible that different countries have experienced different trends because of differences in the physical or social environment.3 For example, smoking, the use of agricultural pesticides, the availability of purified water, or head trauma, which have all been implicated as either potential protective or risk factors for Parkinson's disease, might have decreased in some countries but increased or remained stable in other countries.3 Therefore, we urgently need high-quality sources of data on incidence, prevalence, and risk or protective factors for Parkinson's disease in different countries or regions.
With the aging of the population, the burden of Alzheimer's disease (AD) is rapidly expanding. More than 5 million people in the US alone are affected with AD and this number is expected to triple by ...2050. While men may have a higher risk of mild cognitive impairment (MCI), an intermediate stage between normal aging and dementia, women are disproportionally affected with AD. One explanation is that men may die of competing causes of death earlier in life, so that only the most resilient men may survive to older ages. However, many other factors should also be considered to explain the sex differences. In this review, we discuss the differences observed in men versus women in the incidence and prevalence of MCI and AD, in the structure and function of the brain, and in the sex-specific and gender-specific risk and protective factors for AD. In medical research, sex refers to biological differences such as chromosomal differences (eg, XX versus XY chromosomes), gonadal differences, or hormonal differences. In contrast, gender refers to psychosocial and cultural differences between men and women (eg, access to education and occupation). Both factors play an important role in the development and progression of diseases, including AD. Understanding both sex- and gender-specific risk and protective factors for AD is critical for developing individualized interventions for the prevention and treatment of AD.
A growing body of epidemiologic evidence indicates a decline in the incidence or prevalence of dementia in high income countries in the past 25 years. In this commentary, I first suggest that the ...decline in the incidence or prevalence of dementia is not explained completely by the factors considered so far, and that a broader historical perspective may be needed. Second, I suggest that the overall declining trend may conceal trends in opposite directions for the two major subtypes of dementia, the neurovascular and the neurodegenerative type. Third, I suggest some areas of future research to further elucidate the trends. The future of dementia remains somewhat unclear. Even if the incidence continues to decline, the prevalence may remain the same or increase if survival of persons affected by dementia increases. In addition, even if the prevalence declines, the total number of persons affected by dementia may remain the same or increase if the size of the elderly population expands. Finally, we cannot be sure that the decline in incidence will continue in the coming decades. With cautious optimism, we may conclude that the burden of dementia may be modified over time by human practices, including public health and medicine.
Linked article: This is a mini commentary on Panayotes Demakakos et al., pp. 1482–1490 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17088
To study the association between bilateral oophorectomy and the rate of accumulation of multimorbidity.
In this historical cohort study, the Rochester Epidemiology Project records-linkage system was ...used to identify all premenopausal women who underwent bilateral oophorectomy before age 50 years between January 1, 1988, and December 31, 2007, in Olmsted County, Minnesota. Each woman was randomly matched to a referent woman born in the same year (±1 year) who had not undergone bilateral oophorectomy. We studied the rate of accumulation of 18 common chronic conditions over a median of approximately 14 years of follow-up.
Although women who underwent bilateral oophorectomy already had a higher multimorbidity burden at the time of oophorectomy, they also experienced an increased risk of subsequent multimorbidity. After adjustments for 18 chronic conditions present at baseline, race/ethnicity, education, body mass index, smoking, age at baseline, and calendar year at baseline, women who underwent oophorectomy before age 46 years experienced an increased risk of depression, hyperlipidemia, cardiac arrhythmias, coronary artery disease, arthritis, asthma, chronic obstructive pulmonary disease, and osteoporosis. In addition, they experienced an accelerated rate of accumulation of the 18 chronic conditions considered together (hazard ratio, 1.22; 95% CI, 1.14-1.31; P<.001). Several of these associations were reduced in women who received estrogen therapy.
Bilateral oophorectomy is associated with a higher risk of multimorbidity, even after adjustment for conditions present at baseline and for several possible confounders. However, several of these associations were reduced in women who received estrogen therapy.
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•The effects of estrogen on the brain vary with age at the time of treatment.•Estrogen naturally produced by the ovaries before age 50years is neuroprotective.•Estrogen treatment (ET) ...in early menopause may be neuroprotective (most commonly at ages 50–60years).•ET initiated in late menopause (ages 65–79years) is harmful regardless of the type of menopause.•Women who experience premature or early menopause either naturally or after bilateral oophorectomy should receive ET.
Current evidence suggests that estrogen may have beneficial, neutral, or detrimental effects on the brain depending on age, type of menopause (natural versus induced), or stage of menopause (early versus late), consistent with the timing hypothesis. Three studies have now compared women who underwent bilateral oophorectomy before menopause with referent women and consistently showed an increased risk of cognitive decline and dementia. These studies suggest a sizeable neuroprotective effect of estrogen naturally produced by the ovaries before age 50years. In this article, we focus on neuroprotection as related to cognitive decline and dementia. Several case-control studies and cohort studies also showed neuroprotective effects in women who received estrogen treatment (ET) in the early postmenopausal stage (most commonly at ages 50–60years). The majority of women in those observational studies had undergone natural menopause and were treated for the relief of menopausal symptoms. However, the clinical trials by the Women’s Health Initiative showed that women who initiated ET alone or in combination with a progestin in the late postmenopausal stage (ages 65–79years) experienced an increased risk of dementia and cognitive decline regardless of the type of menopause. Three observational studies have now formally tested the timing hypothesis, and showed that the neuroprotective or harmful effects of estrogen depend on age at the time of initiation of treatment and on stage of menopause. Therefore, women who undergo bilateral oophorectomy before the onset of menopause or women who experience premature or early natural menopause should be considered for hormonal treatment until the average age of natural menopause (around age 50years). Recommendations for the use of ET by women who experience natural menopause at typical ages remain less certain, and more research is needed.
Changes over time in the incidence of parkinsonism and Parkinson disease (PD) remain uncertain.
To investigate secular trends (period effects) and birth cohort trends in the incidence of parkinsonism ...and PD over 30 years in a geographically defined American population.
We used the medical records-linkage system of the Rochester Epidemiology Project to identify incidence cases of PD and other types of parkinsonism in Olmsted County, Minnesota, from 1976 to 2005. All cases were classified by a movement disorder specialist using defined criteria through the review of the complete medical records within the system. The analyses for this study were conducted between May 2015 and January 2016.
Incidence rates of parkinsonism and PD over 30 years. We tested for secular trends (period effects) using negative binomial regression models and for birth cohort effects using age-period-cohort models.
Of 906 patients with parkinsonism, 501 were men, and the median age at onset was 74 years (interquartile range, 66-81 years). Of the 464 patients with PD, 275 were men, and the median age at onset was 73 years (interquartile range, 64-80 years). The overall incidence rates increased significantly over 30 years in men for both parkinsonism (relative risk RR, 1.17 per decade; 95% CI, 1.03-1.33) and PD (RR, 1.24 per decade; 95% CI, 1.08-1.43). These trends were driven primarily by the older age groups. In particular, for men 70 years or older, incidence rates increased for both parkinsonism (RR, 1.24 per decade; 95% CI, 1.07-1.44) and PD (RR, 1.35 per decade; 95% CI, 1.10-1.65). The secular trends were not significant for women overall or in age strata. We observed an increased risk for both men and women born in the 1920 cohort (1915-1924). However, this birth cohort effect was significant only for PD and only in men.
Our study suggests that the incidence of parkinsonism and PD may have increased between 1976 and 2005, particularly in men 70 years and older. These trends may be associated with the dramatic changes in smoking behavior that took place in the second half of the 20th century or with other lifestyle or environmental changes. However, the trends could be spurious and need to be confirmed in other populations.
In recent years, accumulating evidence has suggested that vascular risk factors contribute to Alzheimer disease (AD). Vascular dementia had been traditionally considered secondary to stroke and ...vascular disease. It has been traditionally distinguished from AD, considered to be a purely neurodegenerative form of dementia. However, in light of this more recent literature, it appears that there is a spectrum: ranging from patients with pure vascular dementia to patients with pure AD and including a large majority of patients with contributions from both Alzheimer and vascular pathologies. In this article, we discuss the impact of vascular risk factors on AD and its consequences at the individual level and at the population level by highlighting the concept of attributable risk. We then discuss the key questions and next steps involved in designing a therapeutic trial to control vascular risk factors for the prevention of dementia.
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