Subcortical Dementia Research Articles

Role of apolipoprotein ε4 allele as a predictor in the course and outcome in patients with subcortical vascular dementia

AbstractBackgroundVascular dementia (VaD) is the second most common dementia in elderly and the major contributor being Cerebral Small Vessel Disease (SVD) which has radiological manifestations of White Matter Hyperintensities(WMH), Cerebral Microbleeds and Lacunar infarcts. This study looks into the role of clinico‐demographic profile, genetic factors in terms of Apo E4 status and neuropsychological characteristics in predicting the course and outcome in patients with Subcortical VaD.MethodA prospective cohort study involving 202 patients who were followed up at baseline and subsequently after 1 and 2 years’ time intervals following informed consent and IEC approval with attempt to understand the role of APOE4 positive status as a predictor for cognitive decline. Comparison of Neuropsychological test performance with ANOVA, regression analysis and survival analysis by plotting Kaplan Meier’s curve was done using SPSS v.21.ResultThe major risk factor identified was Hypertension in 92% followed by smoking in 76% and low socioeconomic status in 56% patients. 35.7% of the population had an APO E4 allele positivity. Regression analysis done showed APO E4 positive status as a significant independent predictor of poorer performance in neuropsychological test scores across time periods. However, survival analysis utilizing Kaplan Meir’s plot showed that unlike smoking and WMH (Odds ratio : 2.62) which increased mortality rates more than twofold, APO E4 did not contribute to increased mortality.ConclusionThis study comprehensively looks into the role of APO E4 in VaD and identifies need for prevention of modifiable risk factors like smoking, hypertension, low SES, poor cognitive reserves and WMH which predicts cognitive decline in subcortical VaD and lead to early mortality in patients with VaD. Positive APO E4 allele status significantly affects performance in cognitive assessments but does not appear to predict mortality and hence risk modification needs to be tailored in patients with VaD.

Biobank innovations for chronic cerebrovascular disease with Alzheimer's disease study (BICWALZS)

AbstractBackgroundBiobank Innovations for chronic Cerebrovascular disease With ALZheimer’s disease Study (BICWALZS) aimed to recruit 650 individuals, aged from 40 to 90 years, to investigate how chronic cerebrovascular contribute to the brain changes or brain pathologies related to the Alzheimer’s disease (AD) process.MethodAll participants received comprehensive clinical and neuropsychological evaluations, multi‐modal brain imaging, including magnetic resonance imaging (MRI), magnetic resonance angiography, Flutemetamol positron emission tomography (PET), blood and genetic marker analyses at baseline, and a subset of participants underwent actigraphy monitoring and fibroblast sampling. Participants are to be followed annually with brief clinical assessments, and some subjects with amyloid or subcortical ischemia are evaluated biannually with the full assessment, including neuropsychological, MRI and laboratory tests.ResultsIn total, 543 individuals had volunteered for this study. Among them, 345 individuals with mild cognitive impairment (MCI), 44 individuals with subcortical vascular dementia(SVaD) and 154 individuals with AD dementia (ADD)–were enrolled at baseline.ConclusionThe BICWALZS cohort is a prospective, longitudinal cohort study that recruited participants with a wide age range and a wide distribution of cognitive status (MCI, SVaD and ADD) and it has several strengths in its design and methodologies. Details of the recruitment, study methodology, and baseline sample characteristics are described in this paper.

Changes in Microvascular Morphology in Subcortical Vascular Dementia: A Study of Vessel Size Magnetic Resonance Imaging.

Background: Cerebral small vessel disease is the most common cause of subcortical vascular dementia (SVaD). Unfortunately, conventional imaging techniques do not always demonstrate the microvascular pathology that is associated with small vessel disease. The purpose of this study was to evaluate the changes in the microvascular structure of SVaD and to identify how the microvascular changes in vessel size, detected with imaging, affect the gray matter.Methods: Ten SVaD patients and 12 healthy controls underwent vessel size imaging with gradient-echo and spin-echo sequences before and after contrast agent injection. Four microvessel index maps, including total blood volume fraction (BVf), mean vessel density (Q), mean vessel diameter (mVD), and vessel size index (VSI) were calculated. ROI value of each microvessel parameter was compared between SVaD patients and controls. Voxel-wise comparison of microvessel parameters was also performed to assess the regional difference. The relationship between the microvessel parameters in white matter and total gray matter volume (TGV) were assessed.Results: Both mVD and VSI were significantly different between the SVaD and controls in the ROI-based comparisons (unpaired t-test, p < 0.05). mVD and VSI were significantly increased in the SVaD group at the subcortical, periventricular white matter, basal ganglia, and thalami compared with the controls (FDR corrected, p < 0.05). VSI in the white matter areas were significantly negatively correlated with TGV (r = −0.446, p < 0.05).Conclusions: The increase of mVD and VSI in SVaD patients reflects the damage of the microvessels in the white matter, and these changes may lead to the damage of the gray matter.

Relationship between thyroid dysfunction and dementia

BackgroundThyroid hormones are essential for normal development and function of the central nervous system. Thyroid dysfunction is associated with many neuropsychiatric disorders mainly cognitive impairment.ResultsWe found a close correlation between thyroid status and cognitive dysfunction. Serum FT3 levels decreased, whereas the serum thyroid-stimulating hormone (TSH) level increased, with the decline in cognitive functions. Furthermore, the TSH level showed a negative correlation with the Mini-Mental State Examination (MMSE) scores. We suggested that thyroid function was associated with cognitive impairments induced by subcortical ischemic vascular dementia (SIVD).ConclusionWe found that thyroid dysfunction especially subclinical hypothyroidism is associated with cognitive impairment. Dementia increases more with more increase in TSH, and the MMSE score decreases with the increase of age.

Prevention of suffering with subcortical parkinsonian dementia

Background: Complications of subcortical parkinsonian dementia is characterized by difficulty remembering things, focusing and making judgments.

An Iatrogenic Model of Brain Small-Vessel Disease: Post-Radiation Encephalopathy.

We studied 114 primitive cerebral neoplasia, that were surgically treated, and underwent radiotherapy (RT), and compared their results to those obtained by 190 patients diagnosed with subcortical vascular dementia (sVAD). Patients with any form of primitive cerebral neoplasia underwent whole-brain radiotherapy. All the tumor patients had regional field partial brain RT, which encompassed each tumor, with an average margin of 2.6 cm from the initial target tumor volume. We observed in our patients who have been exposed to a higher dose of RT (30–65 Gy) a cognitive and behavior decline similar to that observed in sVAD, with the frontal dysexecutive syndrome, apathy, and gait alterations, but with a more rapid onset and with an overwhelming effect. Multiple mechanisms are likely to be involved in radiation-induced cognitive impairment. The active site of RT brain damage is the white matter areas, particularly the internal capsule, basal ganglia, caudate, hippocampus, and subventricular zone. In all cases, radiation damage inside the brain mainly focuses on the cortical–subcortical frontal loops, which integrate and process the flow of information from the cortical areas, where executive functions are “elaborated” and prepared, towards the thalamus, subthalamus, and cerebellum, where they are continuously refined and executed. The active mechanisms that RT drives are similar to those observed in cerebral small vessel disease (SVD), leading to sVAD. The RT’s primary targets, outside the tumor mass, are the blood–brain barrier (BBB), the small vessels, and putative mechanisms that can be taken into account are oxidative stress and neuro-inflammation, strongly associated with the alteration of NMDA receptor subunit composition.

Significance of Basal ganglia calcification in Down's syndrome

Purpose There is high incidence of dementia in individuals with Down’s syndrome. Much of the emphasis has been on Alzheimer’s disease as being most prevalent; however, it is apparent that other dementia types are also likely, to which this patient cohort may be predisposed. Specifically, this paper aims to highlight the potential for subcortical dementias in Down’s syndrome, suggesting a role for broader cognitive screening in aging individuals. Design/methodology/approach This paper describes a case of a female with Down’s syndrome and mild intellectual disability who presented with early signs of distinctive cognitive impairment and radiological calcification of the basal ganglia. Findings An active 42-year-old lady, who was mostly independent of activities of daily living and in part-time employment, presented with a three-year history of progressive cognitive deficit, characteristic of subcortical decline. She had no personal or known family history of mental illness, epilepsy or dementia. Routine blood tests showed chronic renal impairment, mild hypocalcaemia and vitamin D deficiency, managed by her GP. CT scan showed only bilateral basal ganglia calcification. Originality/value There is a widespread appreciation for the link between Down’s syndrome and Alzheimer’s disease but lesser consideration of the possibility of subcortical dementias. Given the differential nature and presentation of the two dementias, this case report highlights a need for clinicians to consider both to effectively manage these patients in the longer-term. Screening is discussed as a potential means of achieving this.

Behavior in subcortical vascular dementia with sight pathologies: visual hallucinations as a consequence of precocious gait imbalance and institutionalization.

Subcortical vascular dementia (sVAD) is considered the most frequent dementia in old population, and it is due to a small vessel disease. It has a very specific nosography, where the dominant factors are dysexecutive functions, depression, and apathy. Very few studies described visual hallucinations in sVAD, apart from in the final stages of it. This study recruited 577 patients with a diagnosis of sVAD associated with major ocular pathologies and 1118 patients with sVAD without any significant ocular pathology: Patients were followed up for 24months. We studied the influence of ocular pathologies in precocious visual hallucinations, on behavior disorder (aggressiveness), and gait disorders (instability, fells). We registered the necessity of neuropsychiatric therapies, incidence of hospitalization, and institutionalization. What emerges from our study is that the ocular comorbidities might change the behavior profile of dementia, provoking behavioral alterations, and the need for therapies with adverse effects. As far as old age is a complicated status of life, many factors can modify its development. The possible contribution of multiple biological events cannot be neglected, particularly the underlying influence of chronic diseases as well as the geriatric conditions, per se, might compromise the cognitive functions and the pathological conditions. Ocular pathology as a superimposing event in sVAD might worse the outcome. A correct and rapid identification of critical patients might be relevant for the dynamic life events in these patients and their caregivers.

Tetradecyl 2,3-dihydroxybenzoate alleviates oligodendrocyte damage following chronic cerebral hypoperfusion through IGF-1 receptor

Currently, there is no effective therapy for chronic cerebral hypoperfusion-induced subcortical ischemic vascular dementia (SIVD), which displays cognitive deficits and progressive white matter damage. Tetradecyl 2,3-dihydroxybenzoate (ABG-001) is a lead compound derived from gentisides with neuritogenic activity. In this report, we intended to investigate the effect of ABG-001 on the SIVD experimental model through right unilateral common carotid arteries occlusion (rUCCAO) in mice. We found that ABG-001 remarkably alleviated white matter damage and cognitive deficits after cerebral hypoperfusion induced by rUCCAO. The protection of ABG-001 on the white matter was related to an amelioration of the oligodendrocyte apoptosis and demyelination rather than promoting remyelination. Molecular docking study showed that ABG-001 possesses a high affinity for insulin-like growth factor-1 receptor (IGF-1R), but not for tropomyosin receptor kinase A (TrkA). The protection of ABG-001 against oligodendrocyte damage was abrogated by IGF-1R antagonist or knockdown of IGF-1R through shRNA, but not TrkA antagonist. Moreover, ABG-001 did not induce hematological, renal or hepatic toxicity after chronic treatment. The present study indicates that ABG-001 protects oligodendrocytes through IGF-1R to relieve demyelination following chronic cerebral hypoperfusion, which could be represented as an encouraging treatment for SIVD.

Small Vessel Disease-Related Dementia: An Invalid Neurovascular Coupling?

The arteriosclerosis-dependent alteration of brain perfusion is one of the major determinants in small vessel disease, since small vessels have a pivotal role in the brain’s autoregulation. Nevertheless, as far as we know, endothelium distress can potentiate the flow dysregulation and lead to subcortical vascular dementia that is related to small vessel disease (SVD), also being defined as subcortical vascular dementia (sVAD), as well as microglia activation, chronic hypoxia and hypoperfusion, vessel-tone dysregulation, altered astrocytes, and pericytes functioning blood-brain barrier disruption. The molecular basis of this pathology remains controversial. The apparent consequence (or a first event, too) is the macroscopic alteration of the neurovascular coupling. Here, we examined the possible mechanisms that lead a healthy aging process towards subcortical dementia. We remarked that SVD and white matter abnormalities related to age could be accelerated and potentiated by different vascular risk factors. Vascular function changes can be heavily influenced by genetic and epigenetic factors, which are, to the best of our knowledge, mostly unknown. Metabolic demands, active neurovascular coupling, correct glymphatic process, and adequate oxidative and inflammatory responses could be bulwarks in defense of the correct aging process; their impairments lead to a potentially catastrophic and non-reversible condition.

Cerebrall Autosomal Dominant Artheriopathy with Subcortical Infarcts and Leukoencephalopathy

CADASIL is a hereditary cerebrovascular disease that affects small vessels and usually causes recurrent subcortical infarctions with white matter involvement. It is usually closely related to migraine history, in advanced cases a subcortical dementia usually occurs. It is a disease characterized by a picture of progressive deterioration, and in very advanced stages a pseudobulbar paralysis can occur. In 1955 some cases were described that were called hereditary vascular dementia, later in 1977 it was renamed hereditary multi-infarct dementia, in 1991 they came to be referred to as familial arteriopathic leukoencephalopathy [1]. Finally, with the discovery of the gene involved in the disease, it was renamed CADASIL in 1996 by Joutel. As we can see, the pathological discovery of the disease is of recent discovery, thus adopting the various nomenclatures described above.

Combined Transcriptomic and Proteomic Analyses of Cerebral Frontal Lobe Tissue Identified RNA Metabolism Dysregulation as One Potential Pathogenic Mechanism in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL).

Cerebral small vessel disease (SVD) is an important cause of stroke and vascular cognitive impairment (VCI), leading to subcortical ischemic vascular dementia. As a hereditary form of SVD with early onset, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) represents a pure form of SVD and may thus serve as a model disease for SVD. To date, underlying molecular mechanisms linking vascular pathology and subsequent neuronal damage in SVD are incompletely understood. We performed comparative transcriptional profiling microarray and proteomic analyses on post-mortem frontal lobe specimen from 2 CADASIL patients and 5 non neurologically diseased controls in order to identify dysregulated pathways potentially involved in the development of tissue damage in CADASIL. Transcriptional microarray analysis of material extracted from frontal grey and white matter (WM) identified subsets of up- or down-regulated genes enriched into biological pathways mostly in WM areas. Proteomic analysis of these regions also highlighted cellular processes identified by dysregulated proteins. Discrepancies between proteomic and transcriptomic data were observed, but a number of pathways were commonly associated with genes and corresponding proteins, such as: "ribosome" identified by upregulated genes and proteins in frontal cortex or "spliceosome" associated with down-regulated genes and proteins in frontal WM. This latter finding suggests that defective expression of spliceosomal components may alter widespread splicing profile, potentially inducing expression abnormalities that could contribute to cerebral WM damage in CADASIL.

Microglial Hv1 proton channels promote white matter injuries after chronic hypoperfusion in mice.

Microglia are critical in damage/repair processes during ischemic white matter injury (WMI). Voltage-gated proton channel (Hv1) is expressed in microglia and contributes to nicotinamide adenine dinucleotide phosphate oxidase complex-dependent production of reactive oxygen species (ROS). Recent findings have shown that Hv1 is involved in regulating luminal pH of M1-polarized microglial phagosomes and inhibits endocytosis in microglia. We previously reported that Hv1 facilitated production of ROS and pro-inflammatory cytokines in microglia and enhanced damage to oligodendrocyte progenitor cells from oxygen and glucose deprivation. To investigate the role of Hv1 in hypoperfusion-induced WMI, we employed mice that were genetically devoid of Hv1 (Hv1-/- ), as well as a model of subcortical vascular dementia via bilateral common carotid artery stenosis. Integrity of myelin was assessed using immunofluorescent staining and transmission electron microscopy, while cognitive impairment was assessed using an eight-arm radial maze test. Hv1 deficiency was found to attenuate bilateral common carotid artery stenosis-induced disruption of white matter integrity and impairment of working memory. Immunofluorescent staining and western blotting were used to assay changes in oligodendrocytes, OPCs, and microglial polarization. Compared with that in wild-type (WT) mice, Hv1-/- mice exhibited reduced ROS generation, decreased pro-inflammatory cytokines production, and an M2-dominant rather than M1-dominant microglial polarization. Furthermore, Hv1-/- mice exhibited enhanced OPC proliferation and differentiation into oligodendrocytes. Results of mouse-derived microglia-OPC co-cultures suggested that PI3K/Akt signaling was involved in Hv1-deficiency-induced M2-type microglial polarization and concomitant OPC differentiation. These results suggest that microglial Hv1 is a promising therapeutic target for reducing ischemic WMI and cognitive impairment.

White Matter Hyperintensities Relate to Basal Ganglia Functional Connectivity and Memory Performance in aMCI and SVMCI.

Cerebral small vessel diseases play a crucial role in both vascular and non-vascular dementias. The location of white matter hyperintensities (WMHs), a neuroimaging marker of cerebral small vessel disease, has been found to vary between different types of dementias, and those in the basal ganglia (BG) have been particularly associated with vascular cognitive impairment (VCI). However, anatomical variation of WMHs across BG nuclei and its effect on brain network dysconnectivity has not been clearly elucidated. The study sample consisted of 40 patients with amnestic mild cognitive impairment (aMCI), 40 with subcortical vascular MCI (SVMCI), and 40 healthy control subjects. We examined the volume of WMH using T2-weighted magnetic resonance imaging. We also assessed the disturbances in BG-cortical communication by measuring resting-state functional connectivity (rsFC) from the functional magnetic resonance imaging signal. WMHs were more pronounced in the SVMCI group particularly in the caudate regions. In SVMCI patients, while higher WMHs in the dorsal caudate correlated with weaker FC with executive control regions and worse immediate recall performance, WMHs in the ventral caudate were associated with weaker FC with anterior default mode regions and worse delayed recall performance. In contrast, in aMCI patients, BG WMHs were not correlated with their changes in functional connectivity changes, which showed weaker connectivity with almost all BG structures, rather than restricting to specific BG subdivisions as observed in the SVMCI group. Our findings demonstrate that heterogeneously distributed BG WMHs are associated with changes in functional network interactions and verbal episodic memory performance only in SVMCI patients, which establishes a link between cerebrovascular-related structural abnormality, functional integrity of BG circuits, and episodic memory impairments in SVMCI, and may reflect a differential role of the cerebrovascular pathology in disrupting network-level communications and cognition between Alzheimer’s and subcortical vascular dementia.

Treadmill Exercise Suppresses Cognitive Decline and Increases White Matter Oligodendrocyte Precursor Cells in a Mouse Model of Prolonged Cerebral Hypoperfusion.

Clinical evidence suggests that patients with subcortical ischemic vascular dementia (SIVD) perform better at cognitive tests after exercise. However, the underlying mechanism for this effect is largely unknown. Here, we examined how treadmill exercise changes the cognitive function and white matter cellular pathology in a mouse model of SIVD. Prolonged cerebral hypoperfusion was induced in 2-month-old male C57BL/6J mice by bilateral common carotid artery stenosis. A week later, the mice were randomly divided into a group that received 6-week treadmill exercise and a sedentary group for observation. In multiple behavioral tests (Y-maze, novel object recognition, and Morris water maze tests), the treadmill exercise training was shown to ameliorate cognitive decline in the hypoperfused SIVD mice. In addition, immunohistological analyses confirmed that there was a larger population of oligodendrocyte precursor cells in the subventricular zone of exercised versus sedentary mice. Although further investigations are needed to confirm a causal link between these findings, our study establishes a model and cellular foundation for investigating the mechanisms through which exercise preserves cognitive function in SIVD.

Can behavioral symptoms differentiate cortical from subcortical dementia - A comparative study of behavioral profile of Parkinson’s disease dementia and behavioral variant of frontotemporal dementia

Patients of behavioural variant of frontotemporal dementia (bvFTD) exhibit prominent behavioural abnormalities along with executive dysfunction. Whereas executive dysfunction is also common in subcortical dementias because of disturbance in fronto-subcortical connection, behavioural symptoms are less frequent. To determine the frequencies of behavioural symptomatology of patients with subcortical (Parkinson's disease with dementia or PDD) and frontal cortical dementia (behavioural variant of Frontotemporal dementia or bvFTD) and to find out the discriminating value of behavioural characteristics in differentiating these two group of patients. Patients were consecutively recruited from Cognitive and Movement Disorder Clinics following standard diagnostic criteria. A total 20 bvFTD and 20 PDD patients were recruited. Behavioural symptoms were noted from reliable caregiver following the questionnaire prepared by Bathgate et al. (2000). Whereas eating and vegetative behaviour were more frequent in bvFTD (85% vs 45%, p = 0.018), the neuropsychiatric behaviours were more common in PDD group 80.0% vs 50.0%, p = 0.095). Although didn’t achieve statistical significance, other symptoms found to be discriminating in two condition were (i) sensory behaviour (p = 0.056), (ii) cognitive mediated behaviour (p = 0.794), (iii) affect-social behaviour (p = 0.162), and (iv) compulsion-ritual behaviour (p = 0.33). The behaviour related to environmental dependency were not found prominent in either groups (p = 0.155), although utilization behavior and echopraxia were more common in bvFTD. Behavioural abnormalities were more common in bvFTD group with prominent abnormality in eating & vegetative behaviour, sensory behaviour, cognitive mediated behaviour, affect-social behaviour, compulsion-ritual behaviour and the PDD group showed marked neuropsychiatry behavioural abnormalities.

MICROGLIOSISINWHITEMATTER OF THE BRAIN IN CHRONIC HCV-INFECTION: MORPHOLOGICAL STUDY

The course of a chronic HCV infection in 50% of cases is followed by affection of the brain. Its most frequent manifestations are various cognitive and psychogenic and neurological disorders. It is considered they are based on the activation of HCV infected microglial cells and related to this exitotoxic injury of neurons. According to the data of literature similar changes of microglia in white matter play an important role in a pathogenesis of HIV-associated subcortical dementia. Despite active studying the role of microglia in HCV infection, structural changes and tissue reactions of these cells in nervous tissue remain unexplored. In this regard the purpose of this research was comprehensive immunomorphological research of microglia cells in white matter of different departments of brain in HCV infection. Object of a research was autopsy samples of white brain matter from 40 patients died in the outcome of a chronic HCV infection. 20 people deceased without infectious and mental pathology made up the control group. After histological processing by standard methodic microscopic sections of white matter samples were prepared and stained with review and elective stainings. The immunohistochemical research was conducted using antibodies to virus protein NS3 and antibodies to CD68 microglia cells. The evaluation of microglia cells reactive changes in nervous tissue was performed with submitted earlier methodic. Statistical processing of results was carried out by dispersive Kruskal-Wallis analysis using the SSPS application programs. Level of significance p was accepted equal 0,05. It was established that during chronic HCV infection in white matter of the brain occurs productive changes of microglia cells. They are presented with diffuse and focal anizomorphic microgliosis which expressiveness differs depending on departments of the brain develop (p=0,000). The highest rates of a microgliosis are defined in white matter of brain hemispheres and a brainstem (р=0,05). Morphological features of microgliosis during HCV infection include glial knots formation, phagocytic transformation of microglia with prevalence of amoeboid cells, granular globes appearance, rod microglia congestions in a hippocampus and also degenerative changes in perifocal white matter. These changes of a microglia can be considered as a morphological equivalent of infected with HCV microglia cells activation. The revealed changes indicate that the microgliosis is typical morphological feature of brain injury during chronic HCV infection, and it plays an important role in the pathogenesis of the HCV-associated damage of central nervous system.

The impact of vascular burden on behavioural and psychological symptoms in older adults with dementia: the BEVASDE study.

Behavioural and psychological symptoms (BPS) worsen quality of life and increase institutionalization in dementia, but the relationship between BPS and vascular burden on neuroimaging is unclear. Our aim is to explore whether the profile of BPS differs between patients with large-vessel or cortical vascular dementia (cVaD), small-vessel or subcortical vascular dementia (sVaD) and Alzheimer's disease (AD). The BEVASDE study comprised 806 demented patients (cVaD-136, sVaD-184, AD-486) recruited from outpatient consultations in Salamanca and Avila, Spain. The Clinical Dementia Rating Scale (CDR) and the 12-item Neuropsychiatric Inventory (NPI) were used to evaluate dementia severity and BPS. BPS were reported in 98.5%, 97.3% and 96.9% of the cVaD, sVaD and AD cases, respectively. The median NPI score was 36 in both cVaD and sVaD and 34 in AD, with a median number of four symptoms per patient. The most frequent disorders were depression (64.4%), apathy (61.8%) and sleep disturbance (60.5%). Multivariate regression analyses after controlling for possible confounders showed a higher risk of euphoria (p = 0.011), apathy (p = 0.007), irritability (p = 0.002) and sleep disturbance (p = 0.020) in cVaD than in AD and more apathy (p = 0.0001) and irritability (p = 0.0001) in sVaD than in AD. In contrast, AD subjects had a higher risk of delusions (p = 0.007) and hallucinations (p = 0.023) than patients with cVaD as well as more aberrant motor behaviour than both cVaD (p = 0.0001) and sVaD (p = 0.003). BPS are common in dementia and may help in differential diagnosis of the various subtypes. We should inquire about them and treat as necessary.

Longitudinal investigation of spatiotemporal dynamics of blood cell stagnation in cerebral capillaries using optical coherence tomography angiography during subcortical vascular dementia development

Longitudinal investigation of spatiotemporal dynamics of blood cell stagnation in cerebral capillaries using optical coherence tomography angiography during subcortical vascular dementia development

Vascular Mild Cognitive Impairment: Identifying Disease in Community-Dwelling Older Adults, Reducing Risk Factors, and Providing Support. The Osaki-Tajiri and Kurihara Projects.

Vascular mild cognitive impairment (MCI) is a critical disease. Its prognosis includes not only onset of vascular dementia, but also death by cardiovascular disease. The vascular risk factors for vascular MCI are treatable, and appropriate treatment can prevent or delay the progression to dementia. Therefore, this group is an excellent candidate for secondary prevention. However, community-dwelling older adults with vascular MCI are often undetected and are not clinically identified until they develop frank dementia. Furthermore, older adults with undetected vascular MCI often have decreased ability to follow their medication regimens and this poor medication adherence worsens their vascular comorbidities. This vicious cycle needs to be prevented through community-based interventions. There is evidence that treatment of hypertension or diabetes mellitus could lead to a reduced incidence of vascular MCI and dementia. In this review article, we first explain the background and etiology of vascular MCI. We then summarize phenotype of subcortical vascular dementia which is often unrecognized or “hidden” in the community. Then we introduce the Osaki-Tajiri and Kurihara Projects which have been conducted in Northern Japan, as an example of prevention projects aimed to identify early-stage vascular MCI in the community, reduce the risk factors and facilitate their treatment. Early identification of vascular MCI in the community could lead to a large reduction in the dementia burden worldwide. The outreach efforts presented here could be useful in developing secondary prevention strategies targeted to vascular MCI.