Objective

To examine the relationship between midlife milk intake and Parkinson disease (PD) incidence through associations with substantia nigra (SN) neuron density and organochlorine pesticide exposure in decedent brains from the Honolulu-Asia Aging Study.

Methods

Milk intake data were collected from 1965 to 1968 in 449 men aged 45-68 years with postmortem examinations from 1992 to 2004. Neuron density (count/mm(2)) was measured in quadrants from a transverse section of the SN. Additional measures included brain residues of heptachlor epoxide, an organochlorine pesticide found at excessively high levels in the milk supply in Hawaii in the early 1980s.

Results

Neuron density was lowest in nonsmoking decedents who consumed high amounts of milk (>16 oz/d). After removing cases of PD and dementia with Lewy bodies, adjusted neuron density in all but the dorsomedial quadrant was 41.5% lower for milk intake >16 oz/d vs intake that was less (95% confidence interval 22.7%-55.7%, p < 0.001). Among those who drank the most milk, residues of heptachlor epoxide were found in 9 of 10 brains as compared to 63.4% (26/41) for those who consumed no milk (p = 0.017). For those who were ever smokers, an association between milk intake and neuron density was absent.

Conclusions

Milk intake is associated with SN neuron loss in decedent brains unaffected by PD. Whether contamination of milk with organochlorine pesticides has a role in SN neurodegeneration warrants further study.

Objectives

To examine the associations between depressive symptoms, antidepressant use, and duration of use with incident frailty 3 years later in nonfrail women aged 65 and older.

Design

Secondary analysis of the Women's Health Initiative Observational Study (WHI-OS), a prospective cohort study.

Setting

WHI-OS was conducted in 40 U.S. clinical centers.

Participants

Women aged 65 to 79, not frail at baseline.

Measurements

Antidepressant use was assessed through medication container inspection at baseline. Four groups were created according to baseline use and Burnam depression screen (range 0-1, 0.06 cutoff): antidepressant nonusers without depressive symptoms (reference group), antidepressant nonusers with depressive symptoms, antidepressant users without depressive symptoms, and antidepressant users with depressive symptoms. Frailty components included slowness or weakness, exhaustion, low physical activity, and unintended weight loss, ascertained through self-report and physical measurements at baseline and Year 3.

Results

Of 27,652 women at baseline, 1,350 (4.9%) were antidepressant users and 1,794 (6.5%) were categorized as depressed. At Year 3, 4,125 (14.9%) were frail. All groups had a greater risk of incident frailty than the reference group. Odds ratios (ORs) ranged from 1.73 (95% confidence interval (CI) = 1.41-2.12) in antidepressant users who were not depressed to 3.63 in antidepressant users who were depressed (95% CI = 2.37-5.55). All durations of use were associated with incident frailty (<1 year OR = 1.95, 95% CI = 1.41-2.68; 1-3 years OR = 1.99, 95% CI = 1.45-2.74; >3 years OR = 1.60, 95% CI = 1.20-2.14).

Conclusion

In older adult women, depressive symptoms and antidepressant use were associated with frailty after 3 years of follow-up.

Importance

The effect of obesity on late-age survival in women without disease or disability is unknown.

Objective

To investigate whether higher baseline body mass index and waist circumference affect women's survival to 85 years of age without major chronic disease (coronary disease, stroke, cancer, diabetes mellitus, or hip fracture) and mobility disability.

Design, setting, and participants

Examination of 36,611 women from the Women's Health Initiative observational study and clinical trial programs who could have reached 85 years or older if they survived to the last outcomes evaluation on September 17, 2012. Recruitment was from 40 US clinical centers from October 1993 through December 1998. Multinomial logistic regression models were used to estimate odds ratios and 95% CIs for the association of baseline body mass index and waist circumference with the outcomes, adjusting for demographic, behavioral, and health characteristics.

Main outcomes and measures

Mutually exclusive classifications: (1) survived without major chronic disease and without mobility disability (healthy); (2) survived with 1 or more major chronic disease at baseline but without new disease or disability (prevalent diseased); (3) survived and developed 1 or more major chronic disease but not disability during study follow-up (incident diseased); (4) survived and developed mobility disability with or without disease (disabled); and (5) did not survive (died).

Results

Mean (SD) baseline age was 72.4 (3.0) years (range, 66-81 years). The distribution of women classified as healthy, prevalent diseased, incident diseased, disabled, and died was 19.0%, 14.7%, 23.2%, 18.3%, and 24.8%, respectively. Compared with healthy-weight women, underweight and obese women were more likely to die before 85 years of age. Overweight and obese women had higher risks of incident disease and mobility disability. Disability risks were striking. Relative to healthy-weight women, adjusted odds ratios (95% CIs) of mobility disability were 1.6 (1.5-1.8) for overweight women and 3.2 (2.9-3.6), 6.6 (5.4-8.1), and 6.7 (4.8-9.2) for class I, II, and III obesity, respectively. Waist circumference greater than 88 cm was also associated with higher risk of earlier death, incident disease, and mobility disability.

Conclusions and relevance

Overall and abdominal obesity were important and potentially modifiable factors associated with dying or developing mobility disability and major chronic disease before 85 years of age in older women.

Background

Organochlorine pesticides are associated with an increased risk of Parkinson's disease. A preliminary analysis from the Honolulu-Asia Aging Study suggested that heptachlor epoxide, a metabolite from an organochlorine pesticide extensively used in Hawaii, may be especially important. This was a cross sectional analysis to evaluate the association of heptachlor epoxide and other organochlorine compounds with Lewy pathology in an expanded survey of brain organochlorine residues from the longitudinal Honolulu-Asia Aging Study.

Methods

Organochlorines were measured in frozen occipital or temporal lobes in 705 brains using gas chromatography with mass spectrometry. Lewy pathology was identified using hematoxylin and eosin- and α-synuclein immunochemistry-stained sections from multiple brain regions.

Results

The prevalence of Lewy pathology was nearly doubled in the presence versus the absence of heptachlor epoxide (30.1% versus 16.3%, P < 0.001). Although associations with other compounds were weaker, hexachlorobenzene (P = 0.003) and α-chlordane (P = 0.007) were also related to Lewy pathology. Most of the latter associations, however, were a result of confounding from heptachlor epoxide. Neither compound was significantly related to Lewy pathology after adjustment for heptachlor epoxide. In contrast, the association of heptachlor epoxide with Lewy pathology remained significant after adjustments for hexachlorobenzene (P = 0.013) or α-chlordane (P = 0.005). Findings were unchanged after removal of cases of PD and adjustment for age and other characteristics.

Conclusions

Organochlorine pesticides are associated with the presence of Lewy pathology in the brain, even after exclusion of PD cases. Although most of the association is through heptachlor epoxide, the role of other organochlorine compounds is in need of clarification. © 2018 International Parkinson and Movement Disorder Society.

Objective

While excessive daytime sleepiness (EDS) can predate the clinical diagnosis of Parkinson disease (PD), associations with underlying PD pathogenesis are unknown. Our objective is to determine if EDS is related to brain Lewy pathology (LP), a marker of PD pathogenesis, using clinical assessments of EDS with postmortem follow-up.

Methods

Identification of LP was based on staining for α-synuclein in multiple brain regions in a sample of 211 men. Data on EDS were collected at clinical examinations from 1991 to 1999 when participants were aged 72-97 years.

Results

Although EDS was more common in the presence vs absence of LP (p = 0.034), the association became stronger in neocortical regions. When LP was limited to the olfactory bulb, brainstem, and basal forebrain (Braak stages 1-4), frequency of EDS was 10% (4/40) vs 17.5% (20/114) in decedents without LP (p = 0.258). In contrast, compared to the absence of LP, EDS frequency doubled (36.7% [11/30], p = 0.023) when LP reached the anterior cingulate gyrus, insula mesocortex, and midfrontal, midtemporal, and inferior parietal neocortex (Braak stage 5). With further infiltration into the primary motor and sensory neocortices (Braak stage 6), EDS frequency increased threefold (51.9% [14/27], p < 0.001). Findings were similar across sleep-related features and persisted after adjustment for age and other covariates, including the removal of PD and dementia with Lewy bodies.

Conclusions

The association between EDS and PD includes relationships with extensive topographic LP expansion. The neocortex could be especially vulnerable to adverse relationships between sleep disorders and aggregation of misfolded α-synuclein and LP formation.