Cognitive and affective functions in Alzheimer's disease patients with metabolic syndrome

Hishikawa, Nozomi; Fukui, Yoshio; Sato, Kota; Kono, Syoichiro; Yamashita, Toru; Ohta, Yasuyuki; Deguchi, Kentaro

doi:10.1111/ene.12845

Cited by 51 publications

(56 citation statements)

References 18 publications

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“…Interestingly, these features have also been reported as indicators of patients with risk of progression from mild cognitive impairment to AD . In fact, greater cognitive and affective decline was found to occur in AD patients with this set of risk factors when compared to those without, together with more significant pathological white matter changes . Seemingly, these events are not only linked to insulin resistance—a hallmark of T2D—but also to vascular endothelial dysfunction, which is in agreement with the recognized association between pathological alterations in cerebral microvasculature and decreased cognitive function in patients with AD .…”

Section: Comorbidities Of T2d: a Complex Diseasesupporting

confidence: 70%

Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential

Matos

Macedo²,

Rauter

2017

Medicinal Research Reviews

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Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two age-related amyloid diseases that affect millions of people worldwide. Broadly supported by epidemiological data, the higher incidence of AD among type 2 diabetic patients led to the recognition of T2D as a tangible risk factor for the development of AD. Indeed, there is now growing evidence on brain structural and functional abnormalities arising from brain insulin resistance and deficiency, ultimately highlighting the need for new approaches capable of preventing the development of AD in type 2 diabetic patients. This review provides an update on overlapping pathophysiological mechanisms and pathways in T2D and AD, such as amyloidogenic events, oxidative stress, endothelial dysfunction, aberrant enzymatic activity, and even shared genetic background. These events will be presented as puzzle pieces put together, thus establishing potential therapeutic targets for drug discovery and development against T2D and diabetes-induced cognitive decline-a heavyweight contributor to the increasing incidence of dementia in developed countries. Hoping to pave the way in this direction, we will present some of the most promising and well-studied drug leads with potential against both pathologies, including their respective bioactivity reports, mechanisms of action, and structure-activity relationships.

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Section: Comorbidities Of T2d: a Complex Diseasesupporting

confidence: 70%

Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential

Matos

Macedo²,

Rauter

2017

Medicinal Research Reviews

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“…2 There is currently no cure and neuropathological mechanisms, underlying dementia, take place over many years before the overt dementia symptoms emerge. 4,5 Cardiometabolic abnormalities include cardiovascular risk factors such as central obesity, raised triglycerides, low high-density lipoprotein (HDL) cholesterol, hypertension, high blood glucose, and increased inflammation. 4,5 Cardiometabolic abnormalities include cardiovascular risk factors such as central obesity, raised triglycerides, low high-density lipoprotein (HDL) cholesterol, hypertension, high blood glucose, and increased inflammation.…”

Section: Introductionmentioning

confidence: 99%

Risk of dementia associated with cardiometabolic abnormalities and depressive symptoms: a longitudinal cohort study using the English longitudinal study of ageing

Kontari

Smith

2018

Int J Geriat Psychiatry

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Objectives Depression and cardiometabolic abnormalities are independently associated with a high risk of dementia. This study aimed to examine the association of comorbid depressive symptoms and cardiometabolic abnormalities with risk of dementia. Methods The sample comprised 4859 participants aged 50 or older without baseline dementia who took part in the English Longitudinal Study of Ageing (waves 2‐7). Depressive symptoms were assessed using the Center for Epidemiologic Studies‐Depression tool. Cardiometabolic abnormalities were defined as three or more cardiometabolic risk factors (inflammation, central obesity, raised triglycerides, low high‐density lipoprotein [HDL] cholesterol, hypertension, and hyperglycaemia or diabetes). Participants were classified into four groups based on presence of depressive symptoms and cardiometabolic abnormalities. Results were analysed using the Cox proportional hazards regression adjusted for covariates. Results A total of 216 cases of incident dementia were reported over 10 years of follow‐up. The group with high depressive symptoms only had an increased hazard of developing incident dementia during follow‐up (HR = 2.68; 95%CI, 1.70‐4.23), which was attenuated after adjustment for baseline cognition. No evidence was found for an association of overall cardiometabolic abnormalities with incident dementia; though hyperglycaemia, hypertension, and abdominal obesity with depressive symptoms had an unadjusted association with incident dementia. Only low‐HDL cholesterol with depressive symptoms had an adjusted association with incident dementia (HR = 0.18; 95%CI, 0.04‐0.75). Conclusions This work confirms depressive symptoms as a risk factor for incident dementia. However, low HDL‐cholesterol with depressive symptoms may be protective against dementia, though more work is required to confirm this association.

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“…For example, vascular dysfunction may be associated with progression of both amyloid and τ pathology (51). In patients already diagnosed with Alzheimer’s disease dementia and mild cognitive impairment, both cognitive and affective dysfunction were increased among those with insulin resistance (52,53), and treating vascular risk factors helped to slow cognitive decline (54). The strong association between type 2 diabetes and vascular contributions to dementia should be carefully considered when implementing treatment and prevention measures.…”

Section: Toward a Precision Medicine Model For Dementia: Type 2 Diabementioning

confidence: 99%

Type 2 Diabetes, Cognition, and Dementia in Older Adults: Toward a Precision Health Approach

et al. 2016

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IN BRIEF There has been a concurrent dramatic rise in type 2 diabetes and dementia in the United States, and type 2 diabetes shares common genetic and environmental risk factors and underlying pathology with both vascular and Alzheimer’s dementias. Given the ability to identify this at-risk population and a variety of potential targeted treatments, type 2 diabetes represents a promising focus for a precision health approach to reduce the impact of cognitive decline and dementia in older adults.

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Cognitive and affective functions in Alzheimer's disease patients with metabolic syndrome

Abstract: Greater cognitive and affective decline occurs in patients with AD-MetS than in those without. Further, insulin resistance and vascular endothelial dysfunction are strongly correlated with AD-MetS before pathological white matter changes can be observed.

Cited by 51 publications

References 18 publications

Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential

Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential

Risk of dementia associated with cardiometabolic abnormalities and depressive symptoms: a longitudinal cohort study using the English longitudinal study of ageing

Type 2 Diabetes, Cognition, and Dementia in Older Adults: Toward a Precision Health Approach

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