Angela L. Jefferson
Vascular Risk Factors and Midlife Cognition
Vanderbilt University Medical Center
homecirculationvol 129 15vascular risk factors midlife cognition free accesseditorialpdfepubaboutview pdfview epubsections toolsadd favoritesdownload citationstrack citationspermissions shareshare onfacebooktwitterlinked inmendeleyreddit jump tofree accesseditorialpdfepubvascular risk factors midlife cognitionrethinking exposure window angela l jefferson phd angela l jeffersonangela l jefferson vanderbilt memory alzheimers center department neurology vanderbilt university medical center nashville tn search papers author originally published31 mar 2014httpsdoiorg101161circulationaha114008906circulation 201412915481550other versions articleyou viewing recent version article previous versions april 22 2014 previous version 1 connection cerebrovascular health cognition empirical interest scientists century 1894 swiss neurologist otto binswanger described association postmortem cerebrovascular changes including atherosclerosis cognitive impairment preceding death middleaged older adults1 onehundred twenty years later field evolved beyond binswangers seminal work include midlife systemic vascular health factors potential mechanistic drivers abnormal cognitive aging including common form dementia alzheimers disease23article see p 1560in issue circulation yaffe colleagues push envelope reporting longitudinal exposure one vascular risk factors early midadulthood associated worse midlife cognitive performance4 participants coronary artery risk development young adults cardia study 18 30 years age baseline underwent vascular risk factor assessments every 2 5 years 25year period cognitive assessment conducted end followup period included delayed episodic memory rey auditory verbal learning test information processing speed digit symbol coding 1 key aspect executive functioning inhibition assessed stroop testin unadjusted models cumulative exposure vascular risk factor exception total cholesterol individually associated poorer performance 3 cognitive measures midlife however models adjusting excluding participants incident cardiovascular events eg myocardial infarction coronary revascularization congestive heart failure findings less consistent significant effects remained diminished normal levels risk factor defined american heart association guidelines5 unrelated midlife cognitive performance models adjusting age sex race education yet models included key demographic covariates elevated systolic blood pressure diastolic blood pressure fasting blood glucose individually associated poorer cognitive performancecollectively results suggest longitudinal exposure one vascular risk factors across early middle adulthood may modest effects midlife cognitive performance recent literature indicates pathogenesis alzheimers disease unfolds decades latelife clinical symptom manifestation example postmortem evidence abnormal phosphorylated tau ie precursor neurofibrillary tangles associated alzheimers disease found children young adults aged 4 29 years6 neuroimaging evidence suggests infant 4 carriers apolipoprotein e genotype apoe4 susceptibility gene alzheimers disease structural brain differences comparison apoe4negative counterparts7 thus similarly plausible intersection vascular risk exposure initial changes brain structure may occur much earlier previously appreciated although effects may clinically manifest midlife late adulthood current findings yaffe colleagues highlight possibilitythe authors speculate diverse number causal mechanisms account reported associations including ischemia especially subcortical nature alterations amyloid production clearance inflammatory oxidative stressinduced neuronal injury geneenvironment interactions underlying mechanisms probably complex may may reflect causal pathwayif causal mechanism exists least 2 fundamental pathways vascular risk factors negatively impact cognition first prevalent cardiovascular disease eg myocardial infarction congestive heart failure may act mediating variable association vascular risk factors poor cognitive outcomes figure presence prevalent cardiovascular disease rather 1 risk factor drives observations vascular risk factors cognition results yaffe et al remained statistically significant adjusting excluding incident cardiovascular events although effect sizes reduced thus observed pattern results supports alternative explanationa successive pathway injury figure b latter account vascular risk factors hypertension8 diabetes mellitus9 contribute initial pathway injury cognition disrupting brains capillary ultrastructure initial basement membrane morphological changes eg pericytic degeneration10 result compromised bloodbrain barrier permeability microcirculation manifest subtle cognitive changes time vascular risk factor burden contribute prevalent cardiovascular disease interim cardiovascular events create second subsequent pathway injury brain exacerbating smallvessel changes perhaps affecting larger vessels corresponding cognitive declinedownload figuredownload powerpointfigure hypothetical pathways may account association worse vascular health abnormal cognitive changes age mediating pathway b successive pathway injury c epiphenomenon confoundalternatively plausible causal pathway exists reported connection vascular risk factors abnormal cognitive aging epiphenomenological nature one confounding variable could explain phenomenon age vascular risk factors prevalent cardiovascular disease increase age prevalence cognitive impairment shared agerelated biological changes adequately captured chronological age could reasonably account results reported yaffe colleagues figure c another possible epiphenomenon confound socioeconomic status one complex correlates like literacy nutrition habits environmental enrichment versus impoverishment individuals lower socioeconomic backgrounds11 lower literacy levels12 comparison peers higher socioeconomic literacy levels may lower baseline cognitive performance levels engage poorer health choices thereby increasing vascular risk factor burden previous studies cardia cohort11 others13 shown lower socioeconomic status major predictor poorer cardiovascular health outcomes however current study design take account potential impact socioeconomic status literacy level results absence baseline cognitive testing precludes evaluation potential confounding effects interindividual differences literacy socioeconomic status within cohortmuch existing vascular risk factor cognitive aging literature focuses risk exposure single time point likely inadequately capturing risk development burden life course contrast yaffe colleagues leverage longitudinal data 8 examinations spanning 25 years across early adulthood midlife although reported effects small clinical significance unclear key strength study emphasis cumulative temporal exposure one risk factors unfortunately cognitive assessment restricted single evaluation end followup period precludes inferences cumulative burden risk factor affects cognitive trajectorythere additional caveats consider respect results put forth yaffe colleagues first analytic models consider risk factor individually without statistical consideration intercorrelated nature variables eg examining fasting blood glucose without adjusting potential confounding role systolic blood pressure authors advocate capturing exposure duration intensity similarly important capture shared effects vascular risk factors brain health another consideration increasing evidence supports apoe4 effect modifier association midlife vascular risk factor exposure midlife14 latelife cognition15 unfortunately analytic models current study consider possible apoe genotype effects perhaps data unavailable cohort finally light extensive number models analyzed absence correction factor could yielded spurious findings resulting type error replication observations essentialdespite modest limitations current work yaffe colleagues compelling suggests better vascular health early life benefits cognitive aging midlife respect next steps essential need unequivocally establish whether causal connection exists vascular risk factor exposure worse cognitive trajectory whether observations explained epiphenomenon causal connection efficacy therapeutic lifestyle interventions young adulthood midlife determined essential aspects field better understood begin evaluating whether early screening coupled aggressive management vascular risk factors young adulthood warranted reduce public health burden associated costs abnormal cognitive agingdisclosuresnonefootnotesthe opinions expressed article necessarily editors american heart associationcorrespondence angela l jefferson phd vanderbilt memory alzheimers center department neurology vanderbilt university medical center 2525 west end ave 12th floor suite 1200 nashville tn 37203 email email protectedreferences1 binswanger die abgrenzung der allgemeinen progressiven paralyseberl klin wochenschr 1894 3111031105 11371139 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dementia 101002alz12380 181 178190 online publication date 1jan2022 gerber vanwagner l yaffe k terry j rana j reis j sidney 2021 nonalcoholic fatty liver disease cognitive function middleaged adults cardia study bmc gastroenterology 101186s12876021016810 211 online publication date 1dec2021 osborn k liu samuels l moore e cambronero f acosta l bell babicz gordon e pechman k davis l gifford k hohman blennow k zetterberg h jefferson 2018 cerebrospinal fluid amyloid42 neurofilament light relate white matter hyperintensities neurobiology aging 101016jneurobiolaging201803028 68 1825 online publication date 1aug2018 cambronero f liu neal j moore e gifford k terry j nair pechman k osborn k hohman bell sweatt j wang beckman j carr j jefferson 2018 apoe genotype modifies association central arterial stiffening cognition older adults neurobiology aging 101016jneurobiolaging201802009 67 120127 online publication date 1jul2018 bagge c henderson v laursen h adelborg k olsen madsen n 2018 risk dementia adults congenital heart disease circulation 13718 19121920 online publication date 1may2018 april 15 2014vol 129 issue 15 advertisement article informationmetrics 2014 american heart association inchttpsdoiorg101161circulationaha114008906pmid 24687776 originally publishedmarch 31 2014 keywordshypertensioneditorialsblood glucosecholesterolmemory episodicinhibition psychologycardiovascular diseasespdf download advertisement subjectsdiabetes type 2epidemiologyhypertensionprimary prevention