Associations Between Midlife Vascular Risk Factors and 25-Year Incident Dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort

Hypertension is a major health concern in the developed world, and its prevalence increases with advancing age. The impact of hypertension on the function of the renal and cardiovascular systems is well studied; however, its influence on the brain regions important for cognition has garnered less attention. We utilized the Cyp1a1‐Ren2 xenobiotic‐inducible transgenic rat model to mimic both the age of onset and rate of induction of hypertension observed in humans. Male, 15‐month‐old transgenic rats were fed 0.15% indole‐3‐carbinol (I3C) chow to slowly induce renin‐dependent hypertension over a 6‐week period. Systolic blood pressure significantly increased, eventually reaching 200 mmHg by the end of the study period. In contrast, transgenic rats fed a control diet without I3C did not show significant changes in blood pressure (145 mmHg at the end of study). Hypertension was associated with cardiac, aortic, and renal hypertrophy as well as increased collagen deposition in the left ventricle and kidney of the I3C‐treated rats. Additionally, rats with hypertension showed reduced savings from prior spatial memory training when tested on the hippocampus‐dependent Morris swim task. Motor and sensory functions were found to be unaffected by induction of hypertension. Taken together, these data indicate a profound effect of hypertension not only on the cardiovascular‐renal axis but also on brain systems critically important for learning and memory. Future use of this model and approach may empower a more accurate investigation of the influence of aging on the systems responsible for cardiovascular, renal, and neurological health.

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“…; Gottesman et al. ). The Cyp1a1‐Ren2 rat model has not previously been used to study the effects of hypertension on cognition.…”

Section: Discussionmentioning

confidence: 98%

Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning

et al. 2019

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“…Similar to early interventions in midlife to prevent CVD, addressing these modifiable factors to prevent early changes in neurologic health may reduce or delay brain aging. [3][4][5][6]9,10 The innovative component of our study was the use of a composite measure of sensorineural and neurocognitive function as a marker of brain aging. Longitudinal studies found that sensorineural impairments in hearing, vision, and olfaction predict cognitive decline or impairment, [11][12][13][14]17 suggesting that sensorineural functions may be sensitive to early effects of pathophysiologic aging processes or aging changes may occur early in brain regions associated with sensorineural function.…”

Section: Discussionmentioning

confidence: 99%

“…The search for modifiable risk factors for cognitive decline, Alzheimer's disease (AD), and other dementias has been the focus of numerous epidemiological studies. [3][4][5][6][7][8][9][10] In addition to vascular-related risk factors such as hypertension and inflammation, age-related changes in hearing, vision, and olfaction may be early signals of increased risk for these neurologic changes. [11][12][13][14][15][16][17] Several studies reported associations between sensory impairments and development of cognitive impairment or decline, [11][12][13][14][15] and we previously showed that impairments in hearing, vision, or olfaction are associated with worse cognitive function in middle-aged adults 16 and the development of cognitive impairment in older adults.…”

mentioning

confidence: 99%

Brain Aging in Midlife: The Beaver Dam Offspring Study

Schubert

Fischer

Pinto

et al. 2019

J American Geriatrics Society

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OBJECTIVES Middle age has been identified as a critical time period for health later in life. Identifying factors associated with worse brain function in middle‐aged adults may help identify ways to preserve brain function with aging. Our objective was to evaluate factors associated with a novel measure of brain aging in middle‐aged and older adults. DESIGN Longitudinal cohort study. SETTING Beaver Dam Offspring Study (BOSS) baseline (2005‐2008), 5‐year (2010‐2013), and 10‐year examinations (2015‐2017). PARTICIPANTS A total of 2285 adults, 22 to 84 years of age, with complete sensorineural and neurocognitive data at the 5‐year examination. MEASUREMENTS Principal component analysis (PCA) was performed combining 5‐year sensorineural (hearing, vision, olfaction) and cognitive (Trail Making Test A and B, Digit Symbol Substitution Test, Verbal Fluency Test, Auditory Verbal Learning Test) test data. Participants with a standardized PCA score less than −1 were classified as having brain aging. Incident brain aging was defined as a PCA score less than −1 at 10 years among participants who had a PCA score of −1 or higher at 5 years. Logistic regression and Poisson models were used to estimate associations between baseline factors and prevalent or incident brain aging, respectively. RESULTS Older age, being male, current smoking, larger waist circumference, not consuming alcohol, cardiovascular disease, and interleukin‐6 were associated with greater odds of prevalent brain aging, whereas more education and exercise were associated with decreased odds. In addition to age and sex, less than a college education, higher levels of soluble intercellular adhesion molecule‐1, diabetes, depressive symptoms, and history of head injury were associated with an increased 5‐year risk of incident brain aging. CONCLUSION In the current study, vascular and inflammatory factors were associated with a new brain aging marker in middle‐aged and older adults. Many of these factors are modifiable, highlighting the importance of addressing health and lifestyle factors in midlife to potentially preserve function for better brain health later in life. J Am Geriatr Soc 67:1610–1616, 2019

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“…In fact, even in prehypertensive (systolic BP >120 and <140 mm Hg or diastolic BP >80 and <90 mm Hg) middle-aged adults, an elevated systolic BP level was shown to be negatively associated with cognitive performance, including memory and executive function [8]. In a cohort study, prehypertension in midlife was also shown to be associated with increased risk of developing dementia [25]. Another study found significantly worse performance on verbal episodic memory for untreated hypertensive women; even at the prehypertensive level, the predictive performance on memory domain is less satisfactory later in life [7].…”

Section: Hypertension and Cognitive Dysfunction In Midlifementioning

confidence: 99%

Vascular Aging and Cognitive Dysfunction: Silent Midlife Crisis in the Brain

Lin¹,

Cheng²,

Chuang

et al. 2017

Pulse

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Background: Vascular aging may cause cerebral microvascular damage and cognitive dysfunction. There is incremental evidence that consistently implicates arterial stiffness being involved in the manifestation of cognitive impairment in the elderly. However, few investigations have examined the relationship between arterial stiffness and cognitive impairment in midlife. Summary: Past studies inconsistently showed improved cognitive outcomes after antihypertensive therapy in elderly populations. Nevertheless, recent findings revealed that blood-pressure-lowering treatment in young adults might eliminate or halt the progression of the detrimental effects related to arterial stiffness, indicating that younger adults may have more favorable outcomes in cognition than their older counterparts if early intervention is conducted at the subclinical stage. Stiffening of the aorta may lead to an excessive flow pulsatility in the brain that may cause microvascular structural brain damage and worse cognitive performance. Recent investigations have suggested that arterial stiffness is likely to trigger initial silent brain damage, possibly preceding midlife, while the manifestation of cognitive decline and deterioration can be foreseen in the subsequent life span. Key Message: Despite the recent novel findings, definite conclusions on causality between vascular aging and cognitive dysfunction cannot be drawn at present. Further well-powered longitudinal studies with superior neuroimaging indicator, vascular mechanical biomarkers, and sensitive cognitive assessment tools that examine a broad range of age populations may help extend our understanding of the association between vascular aging and cognitive dysfunction throughout the life span.

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Associations Between Midlife Vascular Risk Factors and 25-Year Incident Dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort

Cited by 430 publications

References 34 publications

Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning

Gradual hypertension induction in middle‐aged Cyp1a1‐Ren2 transgenic rats produces significant impairments in spatial learning

Brain Aging in Midlife: The Beaver Dam Offspring Study

Vascular Aging and Cognitive Dysfunction: Silent Midlife Crisis in the Brain

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