Research reported at the Alzheimer’s Association
International Conference (AAIC) 2018 in Chicago highlighted sex differences
associated with dementia and Alzheimer’s disease across the life course,
including the first ever large-scale study of reproductive history and dementia
risk in women.

New results reported at AAIC 2018 suggest:

  • Associations between dementia risk and number of children, number
    of miscarriages, age at first menstrual period, and reproductive period (years
    between first menstrual period and menopause).
  • In a separate study, a correlation between cumulative months
    of pregnancy and Alzheimer’s risk.
  • Re-thinking the long-held thought that hormone therapy
    negatively affects cognition.
  • A need for sex-based standards for cognitive assessments, to
    improve early detection in women.

“More women than men have Alzheimer’s disease or other
dementias; almost two-thirds of Americans with Alzheimer’s are women,”
said Maria Carrillo, PhD, Alzheimer’s Association Chief Science Officer.
According to Alzheimer’s Association 2018 Alzheimer’s Disease Facts and
Figures, of the 5.5 million people age 65 or older with Alzheimer’s in the
United States, 3.4 million are women and 2.0 million are men.

There are a number of potential biological and social
reasons why more women than men have Alzheimer’s or other dementias. The
prevailing view has been that women live longer than men on average, and older
age is the greatest risk factor for Alzheimer’s. However, some research
suggests that the risk for developing Alzheimer’s could be greater for women
due to biological or genetic variations, or even different life experiences,
such as education, occupation or rates of heart disease.

“More research is needed in this area, because having a
better understanding of sex-specific risk factors across the lifespan may help
us discover — and eventually apply — specific prevention strategies for
different populations of people with Alzheimer’s and other dementias,”
Carrillo added.

Link between reproductive
history and dementia risk
Ihe first-ever large-scale epidemiological investigation in the US. of
various aspects of reproductive history and dementia risk, Paola Gilsanz, ScD,
staff scientist, Kaiser Permanente Northern California Division of Research in
Oakland, Calif.; Rachel Whitmer PhD, Professor at UC Davis; and colleagues
found a correlation between risk of dementia and the number of children, number
of miscarriages, age at the time of first menstrual period, age at natural
menopause, and reproductive period (the number of years between first menstrual
period and menopause). Self-reported data from 14 595 women between the ages of
40-55 in 1964-1973 were evaluated.

The researchers found that women in the study with three or
more children had a 12% lower risk of dementia compared to women with one
child. These women continued to be at lower risk of dementia after adjusting
for additional mid- and late-life risk factors, such as body mass index and
stroke history.

The researchers also asked about miscarriage and menstrual
history. They found that each additional report of a miscarriage was associated
with a 9% increased risk of dementia, compared to those women who reported no
miscarriages. On average, women were 13 when they had their first menstrual
period and were 47 at natural menopause. Additionally, women who indicated
having their first menstrual period at age 16 or older were at 31% greater risk
than those who reported having their first menstrual period at 13. Compared to
women who experience natural menopause after age 45, those who experience
natural menopause at 45 or younger were at 28% greater dementia risk adjusting
for demographics.

The average length of reproductive period was 34 years.
Compared to women with reproductive periods of 38-44 years, women with
reproductive periods of 21-30 years were at 33% elevated dementia risk
adjusting for demographics.

Hormone therapy not always
associated with cognitive harm

A new study reported at AAIC 2018 sought to investigate why results from the
influential Women’s Health Initiative-Memory Study (WHIMS) and WHI-Study of
Cognitive Aging (WHISCA) differed from previous findings that suggest a
worsening of cognition associated with hormone therapy.

Carey E. Gleason, PhD, Wisconsin Alzheimer’s Disease
Research Center, University of Wisconsin School of Medicine and Public Health,
Madison, and researchers from Hartford Hospital, Hartford and George Washington
University, D.C., looked at two separate studies published since WHIMS and
WHISCA: the Kronos Early Estrogen Prevention Study-Cognitive and Affective
Study (KEEPS-Cogs); and the Early v. Late Intervention Trial with
Estradiol-Cognitive Endpoints (ELITE-Cog). The results showed:

No negative effect on cognition was measured in women who
had initiated hormone therapy between ages 50-54. In contrast, those who
initiated hormone therapy between ages 65-79 demonstrated reductions in global
cognition, working memory and executive functioning.

Women on hormone therapy with type 2 diabetes also showed a
higher risk of cognitive impairment compared to non-diabetic women on hormone
therapy and diabetic women who were administered placebo treatment, after
controlling for age.

“These findings add to our understanding of the complex
effects of hormones on the brain,” said Gleason. “These data are sorely needed
to guide women’s healthcare during and after the menopausal transition and to
help women make personalised and informed decisions regarding management of
their menopausal symptoms and the prevention of future adverse health outcomes.”