Vascular Risk Factors Decrease the Risk of Cognitive Impairment in Amyotrophic Lateral Sclerosis: A Case-Control Study

Abstract Background The disease-modifying effects of diabetes mellitus (DM), hyperlipidemia, and overweight on risk and prognosis of amyotrophic lateral sclerosis (ALS) have gained significant attention in recent years. However, whether these well-known vascular risk factors increase the cognitive burden in patients with ALS remains unclear. We aim to evaluate the association between vascular risk factors (including hypertension, DM, hyperlipidemia, overweight and smoking) and cognitive function in patients with ALS. Methods Patients with ALS were consecutively recruited between June 2012 and November 2019 from a tertiary referral center for ALS at the West China Hospital. Vascular risk factors were confirmed based on clinical data, while cognitive function was evaluated by the Chinese version of the Addenbrooke’s Cognitive Examination-revised. Case-control design to investigate the association between vascular risk factors and cognitive impairment in ALS. With careful confounder adjustment, multivariable logistic regression analysis was performed separately (for each factor) and accumulatively (based on the sum of factors) to determine the association between cognitive impairment and vascular risk factors in ALS. Results Of 870 patients, 561 (64.5%) were men, the mean age at registeration was 54.1 (11.3) years and 266 had cognitive impairment. No cognitive burden from vascular risk factors was found in patients with ALS. On the contrary, we first observed that DM (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.25–0.98; P = 0.04) and hyperlipidemia (OR, 0.50; 95% CI, 0.26–0.97; P = 0.04) showed protective effects against cognitive decline in ALS, adjusted for age, sex, educational level, site of onset, Revised-ALS Functional Rating Scale score, predominant upper motor neuron phenotype, family history of ALS, and the remaining vascular risk factors. Furthermore, patients with > 2 vascular risk factors showed a significantly lower risk of cognitive impairment (OR, 0.18; 95% CI, 0.07–0.48; P = 0.001). Sensitivity analyses of sex did not substantially reverse the risk estimates. Conclusions DM and hyperlipidemia decrease the risk of cognitive impairment in patients with ALS. The fitness hypothesis in ALS has been tested and expanded in our work.

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Prevalence of hippocampal enlarged perivascular spaces in a sample of patients with hypertension and their relation with vascular risk factors and cognitive function

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2017-316724 ◽

2018 ◽

Vol 89 (6) ◽

pp. 651-656 ◽

Cited By ~ 8

Author(s):

Joan Jiménez-Balado ◽

Iolanda Riba-Llena ◽

Edurne Garde ◽

Marta Valor ◽

Belen Gutiérrez ◽

...

Keyword(s):

Risk Factors ◽

Cognitive Function ◽

Rating Scale ◽

Brain Mri ◽

Treatment Compliance ◽

Vascular Risk Factors ◽

Study Cohort ◽

Perivascular Spaces ◽

Vascular Risk ◽

Verbal Reasoning

ObjectivesThe clinical importance of hippocampal enlarged perivascular spaces (H-EPVS) remains uncertain. We aimed to study their association with vascular risk factors, cognitive function and mild cognitive impairment (MCI).MethodsData were obtained from the ISSYS (Investigating Silent Strokes in hYpertensives, a magnetic resonance imaging Study) cohort, which is a prospective study of patients with hypertension aged 50–70 with no prior stroke or dementia. Participants were clinically evaluated and underwent a cognitive screening test, Dementia Rating Scale-2, which includes five cognitive subscales (attention, initiation/perseveration, conceptualisation, construction and memory). Besides, they were diagnosed with MCI or normal ageing following standard criteria. H-EPVS were manually counted on brain MRI according to a previous scale and defined as extensive when H-EPVS count was ≥7 (upper quartile). Multivariate models were created to study the relationship between H-EPVS, vascular risk factors and cognitive function.Results723 patients were included; the median age was 64 (59–67) and 51% were male. Seventy-two patients (10%) were diagnosed with MCI and 612 (84.6%) had at least 1 H-EPVS. Older age (OR per year=1.04, 95% CI 1.01 to 1.08) and poor blood pressure treatment compliance (OR=1.50, 95% CI 1.07 to 2.11) were independently associated with extensive H-EPVS. Regarding cognitive function, H-EPVS were independently and inversely correlated with verbal reasoning (β=−0.021, 95% CI −0.038 to −0.003). No association was found between H-EPVS and MCI.ConclusionsH-EPVS are a frequent finding in patients with hypertension and are associated with ageing and poor hypertension treatment compliance. Besides, H-EPVS are associated with worse verbal reasoning function.

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Risk factors for cognitive impairment in amyotrophic lateral sclerosis: a systematic review and meta-analysis

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-325701 ◽

2021 ◽

pp. jnnp-2020-325701

Author(s):

Tianmi Yang ◽

Yanbing Hou ◽

Chunyu Li ◽

Bei Cao ◽

Yangfan Cheng ◽

...

Keyword(s):

Risk Factors ◽

Amyotrophic Lateral Sclerosis ◽

Cognitive Impairment ◽

Family History ◽

Rating Scale ◽

Or Education ◽

Increased Risk ◽

Bulbar Onset ◽

History Of ◽

Lateral Sclerosis

ObjectiveCognitive impairment is a common, far-reaching but imperceptible manifestation in patients with amyotrophic lateral sclerosis (ALS). We aimed to identify the risk factors for cognitive impairment in ALS.MethodsWe searched PubMed and EMBASE for cross-sectional, case–control and cohort studies that reported predictors of cognitive impairment in ALS. The obtained data were meta-analysed to generate overall ORs and 95% CIs.ResultsTwenty-seven eligible articles reporting on 6799 individuals were included out of 20 501 records. Nine predictors were identified: C9orf72 (OR 3.62, 95% CI 1.76 to 7.45), dysarthria (OR 2.25, 95% CI 1.20 to 4.22), family history of ALS (OR 1.76, 95% CI 1.18 to 2.61), predominant upper motor neuron (PUMN) phenotype (OR 1.73, 95% CI 1.09 to 2.73) and bulbar onset (OR 1.54, 95% CI 1.28 to 1.87) increased risk factors for cognitive impairment in ALS. ALS Functional Rating Scale-Revised scores, sex, age or education level were not significantly associated with cognitive impairment in ALS. In addition, C9orf72 (OR=5.94) and bulbar onset (OR=2.08) were strong predictors of ALS-frontotemporal dementia. Female sex conferred more susceptibility to executive cognitive impairment than male sex (OR=1.82).ConclusionsPatients with C9orf72 repeat expansion, dysarthria, family history of ALS, PUMN phenotype and bulbar onset had a high risk for cognitive impairment in ALS. These associations may contribute to understanding the heterogeneity of ALS.PROSPERO registration numberCRD42020201085.

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Is apathy in late-life depressive illness related to age-at-onset, cognitive function or vascular risk?

International Psychogeriatrics ◽

10.1017/s1041610204000766 ◽

2004 ◽

Vol 16 (4) ◽

pp. 481-486 ◽

Cited By ~ 27

Author(s):

Indrag K. Lampe ◽

Thea J. Heeren

Keyword(s):

Risk Factors ◽

Cognitive Function ◽

Rating Scale ◽

Late Onset ◽

Late Life ◽

Depressive Illness ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Onset Type ◽

Depressed Patients

Background: Apathy has been shown to be an important feature of degenerative, vascular or traumatic brain disorder. Its presence is associated with high depression scores, higher age, low performance on frontal tasks, and more severe deep white matter hyperintensities. In late-life depression, lack of interest or motivation are often more prominent than depressed mood, especially in the late-onset type. It was hypothesized that in a heterogeneous sample of elderly depressed patients, apathy is associated with late-onset type of depression, cognitive dysfunction or vascular risk factors.Method: The Apathy Evaluation Scale (AES) was administered to twenty-nine elderly (≥60 years) inpatients with a DSM-IV major depression or dysthymic disorder. The severity of the depression was measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) and cognitive function with the Mini-mental State Examination (MMSE). The presence of vascular risk factors was traced in the patient's medical records.Results: Apathy was found in 86% of the patients. The AES-score was correlated with the negative symptom score, but not with total MADRS or MMSE-score. No difference in AES-score between early-onset depressed (n = 16) and late-onset depressed (n = 13) patients was found, and between patients with or without vascular risk.Conclusion: Apathy is a main feature of moderate to severe depressive illness in elderly patients and related to the negative symptoms of the disorder. Further studies should include less severely depressed patients and investigate the relation between depression severity and apathy.

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The Spectrum of Cerebrovascular Disease and Associated Cognitive Decline

The Oxford Handbook of Adult Cognitive Disorders ◽

10.1093/oxfordhb/9780190664121.013.27 ◽

2019 ◽

pp. 574-599

Author(s):

Victoria J. Williams ◽

Steven E. Arnold ◽

David H. Salat

Keyword(s):

Risk Factors ◽

Cognitive Impairment ◽

Cerebrovascular Disease ◽

Cognitive Decline ◽

Vascular Dementia ◽

Structure And Function ◽

Vascular Risk Factors ◽

Vascular Health ◽

Vascular Risk ◽

And Function

Throughout the lifespan, common variations in systemic health and illness contribute to alterations in vasculature structure and function throughout the body, significantly increasing risk for cardiovascular and cerebrovascular disease (CVD). CVD is a prevalent cause of mortality in late life; it also promotes brain alterations, contributing to cognitive decline and, when severe, vascular dementia. Even prior to diseased states, individual variation in CVD risk is associated with structural and functional brain alterations. Yet, how cumulative asymptomatic alterations in vessel structure and function contribute to more subtle changes in brain tissue integrity and function that emerge in late life is unclear. Finally, vascular risk factors are associated with the clinical progression of neurodegenerative diseases such as Alzheimer’s disease (AD); however, recent theory posits that vascular degeneration may serve a contributory role in these conditions. This chapter reviews how lifespan changes in vascular health contribute to degenerative changes in neural tissue and the subsequent development of cognitive impairment and/or vascular dementia. It first discusses associations between vascular risk factors and cognition and also how declining vascular health may lead to cognitive impairment and dementia. Next, it identifies basic aspects of cerebrovascular anatomy and physiology sustaining tissue health and discusses how vulnerabilities of this system contribute to neurodegenerative changes. Finally, it reviews evidence of vascular contributions to AD and presents ideas for future research to better understand the full spectrum of cerebrovascular contributions to brain aging, cognitive decline, and dementia.

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