The relationship between Alzheimer’s disease (AD) and cerebrovascular disease (CVD) is attracting attention. To investigate this complex relationship, it is necessary to focus on biomarkers that can assess AD pathophysiology. Positron emission tomography (PET) to detect amyloid-β (Aβ) can visualize the distribution of Aβ accumulation in the brains of AD patients. Amyloid PET imaging has been evaluated qualitatively, but a quantitative evaluation has also been developed to allow better comparison of data across institutions. Quantitative amyloid PET analysis has been used in the development of many disease-modifying drugs against AD. Cerebrospinal fluid and serum biomarkers have also been developed to investigate Aβ pathology, but the advantage of amyloid PET imaging is its ability to assess Aβ accumulation in a site-specific manner.

Spatial assessment of Aβ accumulation by amyloid PET is useful when investigating its association with CVD. We have revealed that more severe CVD findings are associated with milder Aβ accumulation in patients with AD. Simultaneous presence of Aβ and CVD pathologies, compared to the presence of either pathology alone, has been shown to significantly accelerate the onset of clinical dementia and cognitive decline. To prevent cognitive decline in AD patients, it is important to manage vascular risk factors and prevent CVD.

Cerebrovascular disorders are inherently heterogenous. They entail a variety of clinical, pathological and cognitive features. In recent years, cerebral small vessel disease (SVD) has been at the forefront mainly because it is attributed to a common cause of strokes and responsible for long-term sequalae including disability. Advances in neuroimaging, particularly magnetic resonance imaging (MRI) have expounded on the radiological definition of SVD involving white matter hyperintensities and parenchymal changes whereas it is difficult to appreciate covert pathology in intracranial arteries and arterioles. SVD pathology incorporates small cortical and subcortical infarcts, microinfarcts, microbleeds, perivascular spacing and white matter attenuation. Cerebral vessels undergo loss of smooth muscle cells and disruption of the extracellular matrix within basement membranes with consequences on interstitial fluid drainage. The distribution and quantity of SVD pathology involving both parenchymal lesions and arteriopathy vary with age, gender, vascular risk factors and genetically determined disorders. However, both types of lesions invariably correlate with progression of impairment or worsen cognitive function. SVD is part and parcel of almost all types of dementias. The incorporation of SVD as a biomarker is much warranted in the biological definition of dementia. Therapeutic interventions to reduce SVD pathology via risk control will have a major impact on the burden of dementia.

Cognitive dysfunction and skeletal muscle dysfunction tend to coexist, and the combined condition of MCI and physical frailty is defined as cognitive frailty. In this review, to understand the pathomechanism of skeletal muscle dysfunction in Alzheimer’s disease (AD), the most common cause of cognitive impairment, we first describe the physiological functions of Aβ peptide, the causative factor of AD, and its precursor, APP, in skeletal muscle. Next, the mechanism of skeletal muscle dysfunction associated with AD is discussed based on the findings of inclusion body myositis, which shows pathological conditions similar to AD, such as the accumulation of Aβ42. Then, recent findings on the effects of skeletal muscle secretory peptides on AD pathology will be presented and the physiological significance of the brain-skeletal muscle connection will be discussed. Finally, we will present our experimental results on the skeletal muscle phenotype of AD mouse models and discuss the effects of Alzheimer’s disease causative factors on skeletal muscle.

Graves’ disease, an autoimmune thyroid disease that results in hyperthyroidism, is rarely complicated by progressive stenosis or the occlusion of proximal intracranial arteries. The combination of these two pathologies was classically categorized as “quasi-Moyamoya disease”, but the revised diagnostic criteria for Moyamoya disease established a new disease concept of “Moyamoya disease with Graves’ disease”, for which an appropriate treatment is still unclear. In the present case, a 35-year-old woman showed transient hemiparesis and poor concentration. After serum analysis and brain imaging, she was diagnosed as having Moyamoya disease with Graves’ disease. Her symptoms and radiological findings improved dramatically after medical treatment for Graves’ disease without any other interventions. The present case represents a valuable reference for selecting treatment steps for this rare disease with a unique pathophysiology.