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Alzheimer’s disease (AD) is the most common type of dementia, accounting for approximately 60% of dementia cases (either alone or in combination); vascular dementia (VaD) accounts for another 10–20%. Most epidemiologic research on dementia has examined prevalence, incidence, and risk factors for either all-cause dementia or AD. This chapter discusses the epidemiology of all-cause dementia and AD, as well as advancement in VaD-related risk factors. Numerous prospective, observational studies have identified a variety of factors that may prevent or delay dementia onset. To better understand the epidemiology of dementia and the potential benefits of implementing interventions, future studies need to address the life course and long preclinical aspects of this disorder. More work is needed to understand the epidemiology and risk factors for non-AD or VaD dementias.
Vascular cognitive impairment (VCI) is a cognitive syndrome caused by cerebrovascular disease, and it includes vascular dementia (VaD) and vascular mild cognitive impairment (VaMCI). VaD is characterized by cognitive impairment and imaging evidence of cerebrovascular disease. VaMCI is considered the "vascular" equivalent of mild cognitive impairment. The clinical patterns of VaD differ depending on the vessels involved and the location of vascular lesions. Large vessel disease can cause single or multiple territorial infarctions in cortical or subcortical locations, while small vessel disease usually involves subcortical structures such as the basal ganglia and thalamus. The diagnostic criteria for VaD include the presence of cognitive impairment, imaging evidence of cerebrovascular disease, and a temporal relationship between a vascular event and onset of cognitive deficits. The diagnostic criteria for VaMCI are similar but without the requirement of a temporal relationship. Patients with VaD often have focal neurological deficits, while those with VaMCI may have executive dysfunction and memory deficits. The neuropsychological profile of VaD includes deficits in executive function, attention, and speed, while memory and visuospatial function may be relatively preserved. Patients with VaD may also experience behavioral and affective changes .
Alzheimer’s disease (AD) is the most common type of dementia, accounting for approximately 60% of dementia cases (either alone or in combination); vascular dementia (VaD) accounts for another 10–20%. Most epidemiologic research on dementia has examined prevalence, incidence, and risk factors for either all-cause dementia or AD. This chapter discusses the epidemiology of all-cause dementia and AD, as well as advancement in VaD-related risk factors. Numerous prospective, observational studies have identified a variety of factors that may prevent or delay dementia onset. To better understand the epidemiology of dementia and the potential benefits of implementing interventions, future studies need to address the life course and long preclinical aspects of this disorder. More work is needed to understand the epidemiology and risk factors for non-AD or VaD dementias.
Most people who develop dementia will never be diagnosed, and therefore lack access to treatment and care from specialists in the field. This new edition provides updated guidance on how behavioral symptom reflect the changes occurring in the brain, and how these can help generalist clinicians to accurately diagnose neurodegenerative diseases. This practical book is aimed at healthcare professionals working in neurology, psychiatry and neuropsychology wanting to enhance the skills and knowledge needed to successfully manage these diseases. Simple approaches to bedside mental status testing, differential diagnosis and treatment, and interpreting neuropsychological testing and neuroimaging findings are covered. Introductory chapters outline dementia epidemiology and dementia neuropathology whilst chapters new to this edition describe the improvements in diagnostic capabilities in recent years, including blood based and cerebrospinal biomarkers and emerging biologically based therapies. Chapters on sleep disorders, and chronic traumatic encephalopathy and traumatic brain injury have also been expanded.
Howard CH Khoe, National Psychiatry Residency Programme, Singapore,Cheryl WL Chang, National University Hospital, Singapore,Cyrus SH Ho, National University Hospital, Singapore
Chapter 21 covers the topic of delirium and neurocognitive disorders. Through a case vignette with topical MCQs for consolidation of learning, readers are brought through the diagnosis and treatment of a patient with delirium and neurocognitive disorder. Topics covered include diagnosis, mild and major neurocognitive disorders, types of neurocognitive disorders, risk factors for Alzheimer’s disease, instruments used in evaluation, investigations, pharmacological and non-pharmacological management of neurocognitive disorders, adverse effects of medications, delirium and its diagnosis, pharmacological and non-pharmacological management of delirium, and beahvioural and psychological symptoms of dementia.
Impairments in emotion recognition, a crucial component of social cognition, have been previously demonstrated in patients with behavioral variant frontotemporal dementia (bv-FTD) and Alzheimer’s disease (AD). However, to date, it is unclear whether patients with early-stage vascular dementia (VaD) display deficient emotion recognition. We investigated profiles of impairments in emotion recognition and non-social cognitive functions, comparing VaD patients to bv-FTD and AD patients, and healthy control participants (HC).
Method:
Eighty-one memory clinic patients with early-stage VaD (n = 30), bv-FTD (n = 21) and AD (n = 30), and 40 HCs were included and performed Ekman 60 Faces Test (EFT; emotion recognition), Auditory Verbal Learning Test (AVLT; memory - encoding and retrieval) and Trailmaking Test (TMT A, TMT B, TMT B/A; information processing speed, executive functions). Differences between groups were analyzed with analysis of variance (ANOVA), using age, education and sex adjusted norm Z scores.
Results:
All patient groups performed significantly worse than HCs on EFT (p < .001). Mean performance of VaD patients was in between bv-FTD and AD (only bv-FTD < AD, p < .01). All patient groups were also impaired on AVLT encoding, TMT-B and TMT B/A. Social and non-social neurocognitive functions differed between groups, with specific impairments in processing speed in VaD, emotion recognition in bv-FTD and memory retrieval in AD, and memory encoding and cognitive control impaired in all three groups.
Conclusions:
We found significantly different profiles in VaD, bv-FTD and AD. Assessing emotion recognition has additive value in the distinction between patient groups, allowing for more timely and accurate diagnosis in clinical practice.
Around 55 million people worldwide live with dementia, and more are expected due to population ageing. We aimed to investigate associations between healthy diet and mild cognitive impairment and dementia in 1753 older adults aged 60–64 from the PATH (Personality and Total Health Through Life Cohort) study. Healthy diet was defined by the Mediterranean-DASH diet Intervention for Neurological Delay (MIND) and two dietary guideline quality scores (Dietary Guideline Index (DGI) and Index Diet Quality (IDQ)), which were calculated from baseline FFQ. Higher dietary scores indicated higher diet quality. Incidence of Alzheimer’s disease/vascular dementia (National Institute of Neurological Disorders criteria) and mild cognitive impairment (Winbald criteria) was assessed after 12 years of follow-up using validated questionnaires with nominated proxies. Logistic regression explored associations between dietary scores and cognitive function, adjusting for demographics, lifestyle factors and medical preconditions. Adjusted logistic regression comparing the per unit linear increase in diet scores showed MIND (OR = 0·82, 95 % CI = 0·68, 0·99), but not DGI (0·99 (0·97, 1·00)) or IDQ (1·12 (0·95, 1·32)), was significantly associated with lower odds of developing cognitive impairment. In conclusion, a healthier neuroprotective dietary pattern is associated with better cognitive function over time, whereas dietary patterns generated from general dietary guidelines did not show a significant association. Further research and well-designed clinical studies are needed to determine the effects of the MIND diet on cognitive impairment in older adults without a family history of dementia.
Systemic changes in multiple diseases may influence the onset of dementia. However, the specific temporality between exposure diseases and dementia remains uncertain.
Aims
By characterising the full spectrum of temporal disease trajectories before dementia, this study aims to yield a global picture of precursor diseases to dementia and to provide detailed instructions for risk management and primary prevention of dementia.
Method
Using the multicentre, community-based prospective UK Biobank, we constructed disease trajectories before dementia utilising the phenome-wide association analysis, paired directional test and association quantification. Stratified disease trajectories were constructed by dementia subtypes, gender, age of diagnosis and Apolipoprotein E (ApoE) status, respectively.
Results
Our study population comprised 434 266 participants without baseline dementia and 4638 individuals with all-cause dementia. In total, 1253 diseases were extracted as potential components of the disease trajectory before dementia. We identified three clusters of disease trajectories preceding all-cause dementia, initiated by circulatory, metabolic and respiratory diseases occurring approximately 5–15 years before dementia. Cerebral infarction or chronic renal failure following chronic ischaemic heart disease was the specific trajectory before vascular dementia. Apolipoprotein E (ApoE) ε4 non-carriers exhibited more complex trajectories compared with carriers. Lipid metabolism disorders remained in the trajectories regardless of dementia subtypes, gender, age of diagnosis and ApoE status.
Conclusions
This study provides a comprehensive view of the longitudinal disease trajectories before dementia and highlights the potential targets of midlife cardiometabolic dysfunction for dementia screening and prevention.
Gloria HY Wong, The University of Hong Kong,Bosco HM Ma, Hong Kong Alzheimer's Disease Association,Maggie NY Lee, Hong Kong Alzheimer's Disease Association,David LK Dai, Hong Kong Alzheimer's Disease Association
Readers are presented with 19 case examples of atypical Alzheimer’s disease, other dementias, and conditions resembling dementia. Each case comes with a summary of cognitive and functional assessment results, complaints by informants, clinical history, laboratory examinations indicated, diagnosis, and management, followed by insights from both medical and psychosocial perspectives. These are organised around the following themes: cases illustrative of when imaging and further observation are needed; cases that may be referred to as ‘pseudodementia’, and cases where a decision to refer on may be needed.
Cerebral small vessel diseases (CSVDs) are among the most common age-related pathologies of the brain. Arteriolosclerosis and cerebral amyloid angiopathy (CAA) are the most common CSVDs. In addition to causing stroke and dementia, CSVDs can have diverse covert radiological manifestations on computed tomography and magnetic resonance imaging including lacunes, T2-weighted white matter hyperintensities, increased density of visible perivascular spaces, microbleeds and cortical superficial siderosis. Because they cannot be visualized directly, research on the pathophysiology of CSVD has been difficult. However, advances in quantitative imaging methods, including physiological imaging such as measurement of cerebrovascular reactivity and increased vascular permeability, are beginning to allow investigation of the early effects of CSVD in living people. Furthermore, genomics, metabolomics and proteomics have the potential to illuminate previously unrecognized pathways to CSVD that could be important targets for new clinical trials.
A recent study in Neurology provides the best data yet on the effect of long-term, chronic laxative use on risk of getting dementia. In this 10-year study of 502,229 UK Biobank participants, the regular use of laxatives was associated with a higher risk of all-cause and vascular dementia. At the start of the study, the average age was 57 years, and none of the participants had dementia. Over the subsequent 10 years, 1.3% of those who regularly used laxatives developed dementia. Regular use was defined as taken almost every day. Only 0.4% of those not regularly using laxatives developed dementia. After adjusting for factors such as age, sex, education, other illnesses, and medication use, participants who regularly used laxatives were 1.51 times more likely to develop dementia compared to people who did not regularly use laxatives (hazard ratio = 1.51).
Throughout our lives, our brains undergo a process of gradual, ongoing, and highly variable modifications. It is perfectly normal for people to notice slight cognitive changes by their 50s. This chapter explains how our brain changes throughout our life span. New research on dementia has good news. Just like incidence of heart disease is going down, the incidence of dementia going down! Prevalence, however, or total number of cases, is going up, because there are more older adults in the population than ever before. Research shows life-long healthy habits may cut dementia risk by at least 1/3. Employing healthy habits at age 50 reduces our risk for dementia for at least 24 years. People in Blue Zones develop dementia at a 75% lower rate. Chapter explains the top ten practices to keep brain healthy and high functioning throughout life. Pushing yourself to learn something new helps you develop new neurons and new neural connections. Actions to take explained: Exercise, Mediterranean Diet, participate in Cognitive Training/Stimulation. Engage in creative pursuits. Sleep. Be mindful of medications. Higher education. Wear hearing aids. Watch heath. Avoid social isolation. Celebrate a healthy aging brain.
This study examined the association between loneliness and risk of incident all-cause dementia and whether the association extends to specific causes of dementia.
Design:
Longitudinal.
Setting:
Community.
Participants:
Participants were from the UK Biobank (N = 492,322).
Intervention:
None.
Measurements:
Loneliness was measured with a standard item. The diagnosis of dementia was derived from health and death records, which included all-cause dementia and the specific diagnoses of Alzheimer’s disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD), over 15 years of follow-up.
Results:
Feeling lonely was associated with a nearly 60% increased risk of all-cause dementia (HR = 1.59, 95% CI = 1.51–1.65; n = 7,475 incident all-cause). In cause-specific analyses, loneliness was a stronger predictor of VD (HR = 1.82, 95% CI = 1.62–2.03; n = 1,691 incident VD) than AD (HR = 1.40, 95% CI = 1.28–1.53; n = 3135 incident AD) and was, surprisingly, a strong predictor of FTD (HR = 1.64, 95% CI = 1.22–2.20; n = 252 incident FTD). The associations were robust to sensitivity analyses and were attenuated but remained significant accounting for clinical (e.g. diabetes) and behavioral (e.g. physical activity) risk factors, depression, social isolation, and genetic risk. The association between loneliness and all-cause and AD risk was moderated by APOE ϵ4 risk status such that the increased risk was apparent in both groups but stronger among non-carriers than carriers of the risk allele.
Conclusion:
Loneliness is associated with increased risk of multiple types of dementia.
Stroke is the leading cause of disability worldwide and the second leading cause of death. Large and small strokes and disease of small cerebral blood vessels can lead to dementia, as well as milder degrees of cognitive deficit (vascular cognitive impairment). Strokes may be large or small and may occur with or without bleeding in the brain. The brain can also be damaged by a long-term lack of sufficient blood flow with loss of the axons, needed for neurons to communicate with each other. Attention to the four reserve factors (cognitive, physical, psychological, and social) can help to prevent stroke as well as improve recovery and diminish the effect of stroke on cognitive function. Cerebrovascular disease makes a very important contribution to cognitive impairment with aging. Recent studies have demonstrated several ways in which bacteria that reside in the mouth are involved in causing strokes. There are many modifiable risk factors for stroke including a high-fat diet, obesity, smoking, poor oral hygiene, physical inactivity, atrial fibrillation, alcoholism. Lifestyle factors play a large role in the risk of all forms of stroke
Vascular dementia (VaD) accounts for approximately 15% of all cases of dementia. While there are many different definitions of vascular dementia, it is generally understood to refer to “disease with a cognitive impairment resulting from cerebrovascular disease and ischaemic or haemorrhagic brain injury”. Research suggests that 30% of patients with VaD also suffer from depression. The treatment of depression in VaD with pharmacological therapy is relatively well-established, with the first line drug being a selective serotonin reuptake inhibitor (SSRI). However, a relatively under-researched area is the use of brain stimulation and neuromodulation therapies for the treatment of depression in VaD.
Objectives
This review aims to provide a critical analysis on the efficacy and safety of brain stimulation therapies in treating depression in VaD to determine whether it is an appropriate treatment option.
Methods
The databases used were PubMed and WebofScience. The available literature was analysed which resulted in three papers which met the inclusion criteria and were critically appraised.
Results
In all three studies, depressive symptoms improved after ECT was administered, regardless of the specific tool used to measure the severity of depression. The side effects experienced were also only temporary and resolved independently which speaks to the safety of ECT as a treatment option.
Conclusions
The results of the study prove that ECT is a safe and effective option in treating depression in VaD. However, more research is needed for the medical community to fully understand the different treatment options and say with certainty which is the safest and most effective.
Agitation and psychosis are two common distressing symptoms of dementia. The results of this issue's Cochrane Corner review suggest that, if a pharmacological approach is required, the use of risperidone and other atypical antipsychotics for the purpose of managing these symptoms seems questionable. Furthermore, typical antipsychotics, haloperidol in particular, might have a greater impact on agitation and psychosis than already recognised. This commentary critically appraises the evidence on the efficacy of typical and atypical antipsychotics for agitation and psychosis in dementia.
A large proportion of Alzheimer’s disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity.
Objective:
To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD.
Methods:
We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures.
Results:
Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD).
Conclusion:
These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.
To investigate factors associated with suicidal ideation (SI) around the time of dementia diagnosis. We hypothesised relatively preserved cognition, co-occurring physical and psychiatric disorders, functional impairments, and dementia diagnosis subtype would be associated with a higher risk of SI.
Design:
Cross-sectional study using routinely collected electronic mental healthcare records.
Setting:
National Health Service secondary mental healthcare services in South London, UK, serving a population of over 1.36 million residents.
Participants:
Patients who received a diagnosis of dementia (Alzheimer’s, vascular, mixed Alzheimer’s/vascular, or dementia with Lewy bodies) between 1 Nov 2007–31 Oct 2021: 18,252 people were identified during the observation period.
Measurements:
A natural language processing algorithm was used to identify recorded clinician recording of SI around the time of dementia diagnosis. Sociodemographic and clinical characteristics were also measured around the time of diagnosis. We compared people diagnosed with non-Alzheimer’s dementia to those with Alzheimer’s and used statistical models to adjust for putative confounders.
Results:
15.1% of patients had recorded SI, which was more common in dementia with Lewy bodies compared to other dementia diagnoses studied. After adjusting for sociodemographic and clinical factors, SI was more frequent in those with depression and dementia with Lewy bodies and less common in those with impaired activities of daily living and in vascular dementia. Agitated behavior and hallucinations were not associated with SI in the final model.
Conclusions:
Our findings highlight the importance of identifying and treating depressive symptoms in people with dementia and the need for further research into under-researched dementia subtypes.
The most frequent and severe non-cognitive disorders in dementia are hallucinatory-paranoid disorders (HPD), which cause social dysfunction and financial burden of this pathology.
Objectives
To study the features of HPD in vascular dementia (VD), an approach using clinical-psychopathological, psychometric, psychodiagnostic and mathematical-statistical methods was used.
Methods
The study was based on the examination of 75 patients with HPD in VD and 63 patients with VD without HPD.
Results
In patients with VD in the middle stage of development in the structure of clinical manifestations was dominated by frequent paranoid and paranoid disorders (in 75.6% of patients, p <0.05) with a systemic delusional plot (in 70.1% of patients, p <0.01) material damage, robbery, theft (in 26.8% of patients, p <0.01), relationships (in 21.9% of patients, p <0.01) and jealousy (in 17.1% of patients, p <0, 01), which ran in the form of paranoid delusional disorder (63.4%), acute paranoia (12.2%) and hallucinations (24.4%). In patients with VD in the late stage of development, the clinical and psychopathological structure of GPR was characterized by a predominance of frequent, hallucinatory disorders (82.4% of patients, p <0.01) in the form of healthy (23.5%, p <0.1), tactile (20.6%, p <0.01) and auditory (26.5%, p <0.5) hallucinations, which took the form of hallucinations (44.2%, p <0.05), confusion (61.5 %, p <0.05) and paranoid delusional disorder (17.6%, p <0.01).
Conclusions
The study of the clinical and psychopathological structure of HPD in patients with dementia of different stages of development revealed their dependence on the stage of development of the pathological process.
Patients diagnosed with vascular dementia often present with apathy, executive dysfunction or/and memory impairment. Some of these psychiatric domains are not responsive to antidepressants or acetylcholinesterase inhibitors. Since methylphenidate enhances frontal lobe function, it may be a valid therapeutic option.
Objectives
To report a case where methylphenidate was used as a therapeutic approach in vascular dementia.
Methods
We present a case of a patient diagnosed with vascular dementia with substantial clinical improvement after treatment with methylphenidate.
Results
A 67 year-old male was observed in a psychiatric consultation reporting memory loss, inability to retain information and inattention. According to her spouse, the patient has been mostly isolated at home and recently he has become unable to accomplish some daily living activities. There was no history of previous psychiatric disorder. Cognitive assessment was performed using MoCA test: 19/30 points (predominantly in executive, attention and delayed recall domains). After this evaluation, it was introduced bupropion 150mg od and donepezil 5mg od with insignificant clinical improvement. The patient underwent a routine workup which was unremarkable and a brain computed tomography scan that revealed ischemic leukoencephalopathy. Three months later no clinical benefit was reported. Attention and functional improvement were observed after introduction of methylphenidate with progressive dose adjusting till 30 mg/day.
Conclusions
Besides not being a consensual therapeutic approach, considering that there is a lack of efficient pharmacological strategies in vascular dementia, methylphenidate may play a significant role in this field contributing to clinical improving and ultimately to an enhanced quality of life.