Search

Background: Intermittent fasting (IF) is found to exhibit neuroprotection against various insults, including ischemia; however, IF has been mainly applied before disease onset. It remains unknown whether IF implementation alleviates the long-term detrimental effects of a disease after its establishment., Objectives: To investigate the IF effects on cognitive impairments and cerebrovascular pathologies in a subcortical vascular dementia (SVaD) mouse model., Methods: The SVaD model was developed by inducing hypoperfusion and hyperlipidemia in apoE-deficient (apoE-/-) mice. We subjected 10-week-old apoE-/- mice to bilateral common carotid artery stenosis using micro-coils after they were fed a high-fat diet (HFD; 45% energy) for 6 weeks to induce hyperlipidemia. Age-matched wild-type C57BL/6J mice received sham surgery after undergoing an identical HFD treatment. Both the SVaD model and wild-type mice either started a 1-month IF regimen (time-restricted feeding for 6 hours per day) or continued the standard diet ad libitum (6.2% fat energy) at 8 weeks post-surgery. We assessed mice weight, food intake, and outcomes in a behavioral test battery before, during, and after the IF regimen, prior to histopathological analyses (microvessel density, neuronal density, white matter damage, astrocytosis) of their brains., Results: SVaD model mice on the IF regimen (SVaD-IF) exhibited higher mean recognition and spatial working memory performance compared to SVaD mice fed ad libitum (SVaD-AL; P < 0.01). Additionally, SVaD-IF mice had ∼5% higher hippocampal neuronal density in the dentate gyrus (DG) and cornu ammonis 1 regions than SVaD-AL mice (P < 0.001), which paralleled their post-IF cognitive enhancements. However, SVaD-IF mice showed an ∼50% increase in hippocampal DG astrocytosis compared to SVaD-AL mice (P < 0.05), with no significant differences in microvessel densities among the 2 groups., Conclusions: The improvements in SVaD-IF mice suggest that IF could be a potential nonpharmacological remedy for SVaD. This finding could stimulate future investigations on IF's neuroprotective potential across many neurovascular diseases., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Dementia is one of the greatest public health concerns for the modern aging world. Over the last decade, most researchers developing new therapeutic strategies for dementia have focused on amyloid-β. In contrast, numerous recent studies have indicated that vascular risk factors are associated with various forms of dementia, and that in fact most forms of dementia can be considered an extension of vascular disease. Accordingly, it is sensible to pursue treatment approaches that focus on the blood vessels. Blood-brain barrier (BBB) disruptions in the white matter of patients with vascular cognitive impairment (VCI) have been observed using imaging analysis, and might be potential targets for novel VCI treatment. Tight junctions between cerebral endothelial cells play an important role in the function of the BBB, and recent studies have demonstrated the essential role of microRNAs in regulating tight junctions. Further elucidation of the mechanisms of tight junction-disruption in dementia are likely to lead to promising novel treatments. In this article, we summarize current knowledge regarding microRNAs and vascular cognitive impairment and the possibility of utilizing microRNAs as biomarkers for BBB dysfunction, and seek to envision future therapeutic strategies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent and represent a significant burden for patients and their caregivers. Early recognition and management of these symptoms is crucial as they are associated with increased risk of institutionalization, impairments in daily functioning, reduced quality of life, and more rapid progression to severe dementia. This chapter will discuss the pathophysiology, proposed diagnostic criteria, clinical features, and management of BPSD, including apathy, depression, agitation/aggression, psychosis, and sleep disturbances. Apathy and depression are the most common overall, and apathy is associated with high symptom severity likely because of its greater persistence. Symptoms such as agitation, aggression, hallucinations, and delusions may be especially distressing and dangerous to patients and caregivers. Nonpharmacologic management should be considered first-line therapy in most cases due to the modest and inconsistent evidence base for pharmacologic agents and greater risk of harm. However, the judicious use of pharmacologic agents may be warranted when symptoms are dangerous and/or severely distressing., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Due to the complexity of Alzheimer's disease, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted lipid nanoemulsion) are available. Versatile small molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted "lipid-coated microbubble" [LCM]/"nanoparticle-derived" [ND] (or LCM/ND) nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly class B type I), or SR-BI, making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such film-stabilized microbubbles are well known to substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Transcranial magnetic stimulation (TMS) is emerging as a promising tool to non-invasively assess specific cortical circuits in neurological diseases. A number of studies have reported the abnormalities in TMS assays of cortical function in dementias. A PubMed-based literature review on TMS studies targeting primary and secondary dementia has been conducted using the key words "transcranial magnetic stimulation" or "motor cortex excitability" and "dementia" or "cognitive impairment" or "memory impairment" or "memory decline". Cortical excitability is increased in Alzheimer's disease (AD) and in vascular dementia (VaD), generally reduced in secondary dementias. Short-latency afferent inhibition (SAI), a measure of central cholinergic circuitry, is normal in VaD and in frontotemporal dementia (FTD), but suppressed in AD. In mild cognitive impairment, abnormal SAI may predict the progression to AD. No change in cortical excitability has been observed in FTD, in Parkinson's dementia and in dementia with Lewy bodies. Short-interval intracortical inhibition and controlateral silent period (cSP), two measures of gabaergic cortical inhibition, are abnormal in most dementias associated with parkinsonian symptoms. Ipsilateral silent period (iSP), which is dependent on integrity of the corpus callosum is abnormal in AD. While single TMS measure owns low specificity, a panel of measures can support the clinical diagnosis, predict progression and possibly identify earlier the "brain at risk". In dementias, TMS can be also exploited to select and evaluate the responders to specific drugs and, it might become a rehabilitative tool, in the attempt to restore impaired brain plasticity., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study describes the effects of active music therapy (AMT) on cognition and behaviour in chronic vascular encephalopathy., Design: A single case study investigated different cognitive and psycho-behavioural changes after AMT., Setting: An adult patient with memory, attention, and verbal fluency deficits associated with Vascular Cognitive Impairment-No Dementia (VCI-ND) was treated., Intervention: A four-months AMT course was based on creative and interactive music playing. Sixteen sessions were conducted simultaneously to the pharmacological therapy., Main Outcomes Measures: Cognitive performances, mood, interpersonal interactions, and perceived abilities were assessed using standardized neuropsychological and psycho-behavioural measurements., Results: At baseline, the patient reported a tendency to feel tense, nervous, and angry and difficulties in memory and visuospatial performances, frequently accompanied by attention drops. The social network was a habitual component of the patient's life, but not a source of sharing of personal experiences, safety or comfort. Neuropsychological tests showed deficits in object and figure naming, verbal fluency, short and long-term verbal memory, short-term spatial memory, selective attention, and visuomotor coordination. After AMT, the cognitive profile significantly improved in attention, visuomotor coordination, and verbal and spatial memory. Such positive changes were confirmed at the three-months follow-up. An increase of the interpersonal interactions and consistent reduction of anxiety were also observed., Conclusions: In selected patients with VCI-ND, a well-structured AMT intervention added to standard therapy may contribute in determining a stable improvement of cognitive and psycho-behavioural aspects. Controlled studies are needed to confirm these promising results., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Subcortical vascular dementia (SVD) is a small vessel disease with dementia that exhibits relatively uniform clinical and pathological features and constitutes approximately half of vascular dementia (VaD) cases. This subtype is further classified into Binswanger's disease and multiple lacunar infarctions. The former is characterized by diffuse white matter lesions, and the latter is characterized by lacunar infarctions. Both of these entities are related to hypertensive small vessel changes. Subcortical vascular dementia may exhibit slowly progressive vascular Parkinsonism and dementia but can be differentiated from Alzheimer's disease because it is associated with more extensive white matter lesions, less severe hippocampal atrophy and the absence of cerebral amyloid angiopathy (CAA), which may be indicated radiologically by lobar microbleeds, cortical subarachnoid hemorrhage (SAH) and cortical microinfarctions. Cerebral amyloid angiopathy may manifest as dementia and constitute the cortical type counterpart of SVD in small vessel disease with dementia. This paper provides an overview of the clinical features, pathogenesis and treatment for SVD, as well as its relationship to CAA and Alzheimer's disease., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Depression and cognitive impairment are both common conditions in old age, and frequently occur together. However, accurate figures of the co-occurrence are not available. The inter-relationship between the two clinical entities is still complex and not well understood. Clearly depression can be a psychological reaction to cognitive decline, and thus may also appear as an early symptom in dementing individuals. However, recent data suggest that depression, and in particularly late-life depression, can also be a risk factor for Alzheimer's disease (AD). The relationship between the two clinical entities should be seen in view of observations of white matter changes both in AD and in depression. Since these white matter changes are thought to frequently reflect vascular changes, the concept of "vascular depression" has been advanced. Vascular changes in the brain occur commonly in demented individuals and conversely depression is frequent co-occurrence in vascular disease. Additionally neurotransmitter loss may occur in both, particularly monoaminergic disturbances which is characteristic of depression but may occur also in AD. The same is true for hippocampal atrophy, which is characteristic of AD but has also been described in depression. Here we review the complex relationships between dementia and depression and suggest that excessive release of corticosteroids may have a neurotoxic effects.

Dementia is a common yet potentially underdiagnosed illness in the long-term care setting. Targeted screening for dementia should be routine practice, as a diagnosis of dementia will have benefits to the care of the patient. Assessment of dementia should proceed in a step-wise approach and should be tailored to the needs of the individual patient. Management of dementia involves care for the cognitive changes, behavioral changes, functional changes, and emotional issues. It also involves the management of other illnesses in light of the dementia, consideration of the needs and well-being of the caregiver, and particular attention to advanced care planning. Management techniques and goals should evolve as the patient's illness progresses. This comprehensive approach to management of dementia may reduce morbidity and mortality associated with this illness. This model of care provides patients and families with needed information and resources, a clear view of prognosis, and necessary attention to quality of life issues.

Objective: This study investigated the sleep-promoting, thermoregulatory, and circadian phase-shifting actions of passive body heating (PBH) in elderly insomniac patients (IPs) with mild-to-moderate vascular dementia., Methods: Thirteen elderly IPs with vascular dementia (mean age 76.9 years; male/female ratio 2/11) were subjected to a PBH trial session. This session comprised a 3-day baseline period, 2-day PBH period, and 1-day post-PBH period. In the PBH period, the subjects received PBH (immersion in hot water about 40.0 degrees C to mid-thorax level) for 30 minutes beginning 2 hours before bedtime. Sleep-waking, estimated by actigraph, core body temperature (cBT), and heart rate variability were continuously monitored. Dim-light melatonin-onset time (DLMO) was determined in the baseline and post-PBH periods., Results: PBH significantly improved subjects' sleep quality; sleep latency decreased; sleep efficiency increased; and wake time after sleep onset decreased. These trends were more prominent in the latter half of the sleep time. PBH induced a rapid cBT elevation of approximately 0.80 degrees C, on average, followed by enhanced heat loss (DeltacBT: difference in cBT between just after the PBH and bedtime), lasting 1.5 hours before sleep. There was a significantly positive correlation between DeltacBT and sleep latency. PBH induced no significant phase shift in DLMO. Heart-rate variability data showed that PBH induced parasympathomimetic action during sleep time in the subjects., Conclusion: PBH may have a sleep-promoting effect by intervening in the thermoregulatory and autonomic systems in elderly IPs with vascular dementia.

The existence of vascular dementia (VaD) was first identified by Marie, who described the etat lacunaire, and by Binswanger, who identified white matter lesions in the brain subcortical areas. Alois Alzheimer, when defining the disease now bearing his name, did so in a patient with a presenile onset. The majority of demented elderly people were then believed to have cerebral arteriosclerosis underlying their cognitive decline. The role of cortical vascular lesions, while clear to clinicians, was highlighted only later, by the pathological studies of Tomlinson et al. and the clinical demonstrations of Hachinski et al. who have defined multi-infarct dementia. Lately, the emphasis shifted to pathogenic mechanisms for vascular brain disease with the identification of a multitude of processes, such as lipohyalinosis, cardiac dysfunction and genetic causes, to name only a few. Epidemiologic studies have demonstrated the high frequency of vascular lesions in brains of demented individuals, as well as the fact that vascular factors can contribute to Alzheimer's disease (AD). Moreover, many factors, which were identified as contributing to cerebrovascular disease in general and VaD in particular, are frequently suspected as predisposing to AD as well. All these considerations converge to the realization that vascular components are extremely important in the pathogenesis of old-age dementia and that prevention and perhaps treatment of dementia are within reach. These surprising findings highlight the importance of mixed vascular-degenerative dementia as a disorder that has to be properly defined.

Two important prerequisites for assessing therapeutic benefits in patients with vascular dementia (VaD), or Alzheimer's disease (AD) with cerebrovascular disease (CVD), are the inclusion of appropriate patients and the use of relevant outcome measures. There is substantial overlap in the clinical symptomatology, risk factors, imaging changes, pathophysiology and neurochemical mechanisms between VaD, AD and AD with CVD. While validated and acceptable clinical criteria suitable for clinical trials have been developed for VaD, there is still debate as to how mixed cases (i.e. AD with CVD) are best conceptualized. As with AD, there is consensus that outcome measures in studies of patients with VaD, or AD with CVD, should include assessments of cognitive and global function, of ability to perform activities of daily living (ADL) and of behavioral symptoms. Other measures, e.g., caregiver burden, would be desirable. Care must be taken in extrapolating AD-specific evaluations to VaD, however, because different specific domains are affected and the disease course is different. In clinical trials, cognitive performance and global function decline steadily in patients with untreated AD compared with smaller changes in patients with untreated VaD, while behavior and ADL deteriorate over 6 months in patients with either untreated AD or untreated VaD. Such differences in untreated outcome need to be considered when interpreting trial results using outcome measures that were largely designed for studies of patients with AD.

Vascular dementia (VaD) is increasingly recognised to reflect an outmoded concept in that it identifies cases too late for preventive therapy to have an opportunity to prevent the development of dementia and uses a cognitive paradigm inappropriately based on Alzheimer's disease. A replacement is urgently required and a new concept, that of vascular cognitive impairment (VCI), has been proposed to meet this need. It is imperative that criteria for VCI are developed on the basis of knowledge and data rather than supposition and assumption, as was the case for VaD. This review details the state of knowledge that we have now reached concerning the fundamental points of severity and cognitive paradigm and also covers a number of other imaging-related essential points embracing atrophy, leukoaraiosis, infarct volume and infarct location. Finally, the increasingly important concept of mixed dementia (co-existent Alzheimer's disease and VCI) is discussed.

Background: Preliminary evidence suggests that demented patients may experience beneficial effects of light therapy. The authors tested whether bright light therapy (BLT) is capable of improving cognitive functions in patients with Alzheimer-type dementia (AD) or vascular dementia (VD)., Methods: Twenty-three patients with AD or VD were randomly assigned to either evening BLT or dim light therapy (DLT). Effects of light therapy on cognitive functions were assessed before and after light therapy using Mini-Mental State Examination (MMSE) scores. Body temperature rhythm (BTR) was additionally recorded pre- and posttreatment., Results: Irrespective of their diagnosis, patients treated with BLT (p =.0012) but not with DLT (p =.73) showed a statistically significant increase in MMSE total scores after light therapy. Evening BLT simultaneously induced a significant phase delay of 56 min on BTR (p =.025)., Conclusion: Our preliminary results suggest that short-term evening BLT may exert beneficial effects on cognitive functioning in patients with dementia.