Recent advancements in imaging technologies have provided valuable insights into the pathophysiology and outcomes of various diseases by allowing scientists to track the progression of events within target organs.
A new study published in Alzheimer’s & Dementia leverages imaging discoveries to shed light on the significant variations in Alzheimer’s dementia (AD) presentation based on an individual’s gender.
White matter hyperintensities (WMH) serve as indicators of cognitive decline, leading to mild cognitive impairment (MCI) and, in some cases, dementia. Magnetic resonance imaging (MRI) can visualize these pathologies, which are often attributed to cerebral small vessel disease (CSVD).
WMH may be detected even in the absence of cognitive impairment; however, their presence heightens the risk of decreased cognitive function and MCI in older individuals without other underlying health conditions.
The brain’s small vessels can suffer damage due to a range of health issues, including hypertension, diabetes, obesity, smoking, and excessive alcohol consumption. Interestingly, these factors have differing effects depending on an individual’s gender. For instance, women with high blood pressure, particularly those who are overweight, are more susceptible to strokes than their male counterparts. This disparity may be partly explained by the fact that older women often have higher blood pressure levels and less effective blood pressure management. Menopause may also trigger adverse changes in risk factors for women, leading to sustained elevated blood pressure levels compared to men of the same age. A history of conditions like pre-eclampsia or gestational diabetes during pregnancy can further exacerbate these risks.
Previous research has failed to conclusively establish differences in WMH burden between genders. Nevertheless, some experts believe that these risk factors exert distinct effects on men and women.
The current study uncovers gender-based disparities in WMH progression and the varying impact of different risk factors on this progression, as well as their correlation with cognitive outcomes.
Key Findings
Researchers devised a vascular composite score that included self-reported conditions such as diabetes, alcoholism, smoking, hypertension, and overweight or obesity. Additionally, the Hachinski score, a tool used to assess the presence of vascular disease and vascular dementia, was evaluated.
Participants also underwent cognitive testing, with test results correlated with the WMH burden observed in the latest MRI scans conducted within the past six months.
The study included male participants with an average age of 74 and female participants with an average age of 72. A higher percentage of males (10%) were hypertensive compared to females (5%). Over 50% of males had hypertension, whereas around 45% of females were affected. Furthermore, a larger proportion of males (40%) were smokers compared to females (less than 30%), and alcohol abuse was reported by 6% of males and 2% of females.
Approximately 40% of males and 30% of females received a diagnosis of MCI, while roughly 55% of females and 40% of males were considered cognitively normal.
MRI results revealed age-related increases in WMH progression in nearly all brain regions among women, with exceptions noted in the temporal and parietal regions, where both genders exhibited similar progression rates.
In males, the occipital region displayed a greater WMH burden. The most significant differences were observed in the deep brain and occipital region.
For both genders, WMH progression in all regions except the deep brain correlated with MCI and AD. In women, WMH did not impact the occipital region.
Men with apolipoprotein E (APOE) risk alleles showed higher WMH burdens in the occipital and parietal regions, while women with this genetic risk only exhibited greater WMH burden in the occipital region.
A higher vascular composite score was associated with increased WMH burden in several regions for men, and in all regions for women. Hypertension was linked to greater frontal WMH in males compared to females.
Systolic hypertension was associated with more occipital WMH in males and deeper WMH in females. Importantly, frontal WMH was found to be more closely correlated with vascular disease, while parietal WMH was associated with AD.
Among males, hypertension emerged as the most significant risk factor for WMH occurrence and progression, whereas no single vascular risk factor could be pinpointed among females. However, the vascular composite score correlated with WMH burden in women.
In terms of cognitive decline, both genders were equally affected by WMH. Females, however, exhibited a more pronounced loss of global cognition at the same WMH levels. They also experienced a greater impact on memory and functional status.
These findings align with previous studies indicating that AD manifests at lower levels of brain pathology in females and progresses more rapidly, with greater brain atrophy compared to males. This heightened vulnerability in females may be attributed to reduced estrogen levels, which play a protective role in cognitive function.
Implications
The study underscores the importance of multiple cardiovascular risk factors in modifying the risk of further cognitive decline and WMH progression. Nevertheless, the study reveals that the contribution of various factors differs between males and females, emphasizing the need for gender-specific research in the field of cognitive decline.
