Brain Aging, Cardiovascular Diseases, Mixed Dementia, and Frailty in the Oldest Old: From Brain Phenotype to Clinical Expression

Rosa, Gianmarco; Giannotti, Chiara; Martella, Lucia; Massa, Federico; Serafini, Gianluca; Pardini, Matteo; Nobili, Flavio; Monacelli, Fiammetta

doi:10.3233/jad-191075

Cited by 17 publications

(15 citation statements)

References 154 publications

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“…We were unable to measure exposure to pre-stroke vascular risk factors over time, and this could explain our lack of a finding for hypertension in our study population with its relatively high average age. It has been shown that mid-life hypertension and smoking are associated with cognitive decline, whereas late-life hypertension alone might not be associated ( 3 , 4 , 6 , 7 ), maybe an effect of lower burden of hypertension over time, although selection bias cannot be ruled out as an explanation. Atrial fibrillation, coronary heart disease, and previous stroke can be seen as risk factors that have already exerted an influence on the functioning of the heart, brain, or other organs, indicating a long-lasting and severe exposure to vascular risk factors that may explain our findings.…”

Section: Discussionmentioning

confidence: 99%

“…Hypertension is a known risk factor for dementia; however, knowledge about its association with PSCI is scarce (2)(3)(4)(5). Mid-life hypertension and smoking are associated with cognitive decline, while latelife hypertension alone might not be associated and may even be protective against dementia (3,4,6,7). The STROKOG consortium found associations between cognition and diabetes mellitus, previous stroke, hypertension, atrial fibrillation, and smoking early after a stroke (2).…”

Section: Introductionmentioning

confidence: 99%

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The Impact of Vascular Risk Factors on Post-stroke Cognitive Impairment: The Nor-COAST Study

et al. 2021

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Introduction: Post-stroke cognitive impairment (PSCI) is common, but evidence on the impact of vascular risk factors is lacking. We explored the association between pre-stroke vascular risk factors and PSCI and studied the course of PSCI.Materials and Methods: Vascular risk factors were collected at baseline in stroke survivors (n = 635). Cognitive assessments of attention, executive function, memory, language, and the Montreal Cognitive Assessment (MoCA) were performed at 3 and/or 18 months post-stroke. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). PSCI was measured with global z; MoCA z-score; and z-score of the four assessed cognitive domains. Mixed-effect linear regression was applied with global z, MoCA z-score, and z-scores of the cognitive domains as dependent variables. Independent variables were the vascular risk factors (hypertension, hypercholesterolemia, smoking, diabetes mellitus, atrial fibrillation, coronary heart disease, previous stroke), time, and the interaction between these. The analyses were adjusted for age, education, and sex. There were between 5 and 25% missing data for the variables for PSCI.Results: Mean age was 71.6 years (SD 11.7); 42% were females; and the mean NIHSS score at admittance was 3.8 (SD 4.8). Regardless of vascular risk factors, global z, MoCA, and all the assessed cognitive domains were impaired at 3 and 18 months, with MoCA being the most severely impaired. Atrial fibrillation (AF) was associated with poorer language at 18 months and coronary heart disease (CHD) with poorer MoCA at 18 months (LR = 12.80, p = 0.002, and LR = 8.32, p = 0.004, respectively). Previous stroke was associated with poorer global z and attention at 3 and 18 months (LR = 15.46, p < 0.001, and LR = 16.20, p < 0.001). In patients without AF, attention improved from 3 to 18 months, and in patients without CHD, executive function improved from 3 to 18 months (LR = 10.42, p < 0.001, and LR = 9.33, p = 0.009, respectively).Discussion: Our findings indicate that a focal stroke lesion might be related to pathophysiological processes leading to global cognitive impairment. The poorer prognosis of PSCI in patients with vascular risk factors emphasizes the need for further research on complex vascular risk factor interventions to prevent PSCI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Impact of Vascular Risk Factors on Post-stroke Cognitive Impairment: The Nor-COAST Study

et al. 2021

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“…Although our analyses were not designed to identify the reasons of this heightened vulnerability, a few explanations could be discussed. Emerging evidence suggests subclinical neurovascular changes, including small vessel disease, and/or neurodegenerative processes, such as Lewy body disorders, are common among frail adults 36 ; these processes are known to reduce brain reserve and lower tolerance to stressors 20 . In these participants, a prodromal neurodegenerative profile underlying frailty might have lowered the symptomatic threshold of dopaminergic levels needed to cause slow gait.…”

Section: Discussionmentioning

confidence: 99%

Catechol‐O‐Methyltransferase Genotype, Frailty, and Gait Speed in a Biracial Cohort of Older Adults

Mance

Rosso

Bis

et al. 2020

J American Geriatrics Society

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OBJECTIVE To examine whether the association between dopamine‐related genotype and gait speed differs according to frailty status or race. DESIGN Cross‐sectional population‐based study (Cardiovascular Health Study). SETTING Multicenter study, four U.S. sites. PARTICIPANTS Volunteer community‐dwelling adults aged 65 years and older, without evidence of Parkinsonʼs disease (N = 3,744; 71 years; 82% White; 39% male). MEASUREMENTS Gait speed (usual pace; m/s), physical frailty (Fried definition), and genetic polymorphism of catechol‐O‐methyltransferase (COMT; rs4680), an enzyme regulating tonic brain dopamine levels, were assessed. Interaction of COMT by frailty and by race predicting gait speed were tested, and, if significant, analyses were stratified. Multivariable regression models of COMT predicting gait speed were adjusted for demographics and locomotor risk factors. Sensitivity analyses were repeated, stratified by clinical cutoffs of gait speed (0.6 and 1.0 m/s) instead of frailty status. RESULTS The interaction of COMT by frailty and COMT by race were P = .02 and P = .01, respectively. Compared with Met/Met (higher dopaminergic signaling), the Val/Val group (lower dopaminergic signaling) walked marginally more slowly in the full cohort (0.87 vs 0.89 m/s; P = .2). Gait speed differences were significant for frail (n = 220; 0.55 vs 0.63 m/s; P = .03), but not for prefrail (n = 1,691; 0.81 vs 0.81 m/s; P = .9) or nonfrail (n = 1,833; 0.98 vs 0.97 m/s; P = .7); results were similar in fully adjusted models. Among frail, associations were similar for Whites and Blacks, with statistical significance for Whites only. Associations stratified by clinical cutoffs of gait speed were not significant. CONCLUSION The association of dopamine‐related genotype with gait speed is stronger among adults with frailty compared with those without frailty. The potential effects of dopaminergic signaling on preserving physical function in biracial cohorts of frail adults should be further examined.

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“…VaD comes just after AD as a main cause of dementia, accounting for approximately 15-20% of dementia cases in the Western countries and could reach up to 30% in Asia and developing countries (Rizzi et al, 2014). Vascular deficiencies are now considered relevant contributors to mixed dementia (MxD), which accounts for 25-35% of all dementia cases (Jellinger, 2007;Rosa et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Neurovascular Alterations in Vascular Dementia: Emphasis on Risk Factors

Lecordier

Manrique-Castano

Moghrabi

et al. 2021

Front. Aging Neurosci.

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Vascular dementia (VaD) constitutes the second most prevalent cause of dementia in the world after Alzheimer’s disease (AD). VaD regroups heterogeneous neurological conditions in which the decline of cognitive functions, including executive functions, is associated with structural and functional alterations in the cerebral vasculature. Among these cerebrovascular disorders, major stroke, and cerebral small vessel disease (cSVD) constitute the major risk factors for VaD. These conditions alter neurovascular functions leading to blood-brain barrier (BBB) deregulation, neurovascular coupling dysfunction, and inflammation. Accumulation of neurovascular impairments over time underlies the cognitive function decline associated with VaD. Furthermore, several vascular risk factors, such as hypertension, obesity, and diabetes have been shown to exacerbate neurovascular impairments and thus increase VaD prevalence. Importantly, air pollution constitutes an underestimated risk factor that triggers vascular dysfunction via inflammation and oxidative stress. The review summarizes the current knowledge related to the pathological mechanisms linking neurovascular impairments associated with stroke, cSVD, and vascular risk factors with a particular emphasis on air pollution, to VaD etiology and progression. Furthermore, the review discusses the major challenges to fully elucidate the pathobiology of VaD, as well as research directions to outline new therapeutic interventions.

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Brain Aging, Cardiovascular Diseases, Mixed Dementia, and Frailty in the Oldest Old: From Brain Phenotype to Clinical Expression

Cited by 17 publications

References 154 publications

The Impact of Vascular Risk Factors on Post-stroke Cognitive Impairment: The Nor-COAST Study

The Impact of Vascular Risk Factors on Post-stroke Cognitive Impairment: The Nor-COAST Study

Catechol‐O‐Methyltransferase Genotype, Frailty, and Gait Speed in a Biracial Cohort of Older Adults

Neurovascular Alterations in Vascular Dementia: Emphasis on Risk Factors

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