The Relationship between the Most Common Subtypes of Dementia and Orthostatic Hypotension in Older Adults.

BACKGROUND: It is crucial to evaluate the causes of morbidity and mortality in elderly patients with dementia, such as orthostatic hypotension (OH), which may affect their daily life activities, reduce the quality of life, and increase the caregiver burden. OBJECTIVE: We aimed to investigate the relationship between OH and the most common subtypes of dementia in detail. METHODS: A total of 268 older adults with dementia diagnosed with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and behavioral variant frontotemporal dementia (bvFTD), and 539 older adults without dementia were included in this prospective study. Comprehensive geriatric assessment including comorbidity, medication evaluation, and the head-up tilt test was also performed. RESULTS: Of the participants, 13.8, 8.3, 6.4, and 4.8% had AD, DLB, bvFTD, and VaD, respectively. After adjusting for age, gender, the presence of comorbidities, and usage of OH-induced drugs; AD, DLB, and VaD were associated with OH (odds ratio [OR]: 2.23 confidence interval [CI] 95% 1.31-3.80; p = 0.003; OR: 3.68 CI 95% 1.98-6.83; p < 0.001, and OR: 3.56 CI 95% 1.46-8.69; p = 0.005, respectively). Furthermore, VaD was independently related to diastolic OH (OR: 4.19 CI 95% 1.66-10.57; p = 0.002), whereas AD and DLB were not. CONCLUSIONS: This study shows that elderly patients with DLB, AD, and VaD often have OH, a disabling autonomic dysfunction feature. Moreover, diastolic OH may play a role in the development of VaD. Therefore, considering potential complications of OH, it is essential to evaluate OH in the follow-up and management of those patients.

Prevalence and subtype distribution of early-onset dementia in Japan.

AIM: People living with early-onset dementia (EOD) have specific social needs. Epidemiological studies are needed to obtain current information and provide appropriate service planning. This study aimed to clarify the current prevalence and subtype distribution of EOD, as well as the services frequently used by individuals with EOD. METHODS: A multisite, population-based, two-step study was conducted. Questionnaires were sent to 26 416 candidate facilities in 12 areas with a target population of 11 630 322 to inquire whether any individuals with EOD had sought services or stayed during the last 12 months (step 1). When "yes" responses were received, additional questionnaires were sent to the facilities both to complete and to distribute to the target individuals with EOD to obtain more detailed information, including the dementia subtype (step 2). RESULTS: In step 1, valid responses were obtained from 16 848 facilities (63.8%), and 4077 cases were identified. In step 2, detailed information was obtained for 1614 cases (39.6%) from the facilities and 530 cases (13.0%) from the individuals. The national EOD prevalence rate was estimated to be 50.9/100 000 population at risk (95% confidence interval: 43.9-57.9; age range, 18-64 years). The number of individuals with EOD was estimated to be 35 700 as of 2018. Alzheimer-type dementia (52.6%) was the most frequent subtype, followed by vascular dementia (17.1%), frontotemporal dementia (9.4%), dementia due to traumatic brain injury (4.2%), dementia with Lewy bodies/Parkinson's disease dementia (4.1%), and dementia due to alcohol-related disorders (2.8%). Individuals with EOD were most frequently identified at medical centers for dementia. CONCLUSION: The prevalence rate estimated in this study was comparable to those in previous studies in Japan. However, the subtype distribution differed, with Alzheimer-type dementia being the most prominent. Based on the case identification frequencies, medical centers for dementia are expected to continue to function as the primary special health service by providing quality diagnosis and post-diagnostic support for individuals with EOD.

An Algorithm to Characterize a Dementia Population by Disease Subtype.

PURPOSE: Identification of Alzheimer disease and related dementias (ADRD) subtypes is important for pharmacologic treatment and care planning, yet inaccuracies in dementia diagnoses make ADRD subtypes hard to identify and characterize. The objectives of this study were to (1) develop a method to categorize ADRD cases by subtype and (2) characterize and compare the ADRD subtype populations by demographic and other characteristics. METHODS: We identified cases of ADRD occurring during 2008 to 2014 from the OptumLabs Database using diagnosis codes and antidementia medication fills. We developed a categorization algorithm that made use of temporal sequencing of diagnoses and provider type. RESULTS: We identified 36,838 individuals with ADRD. After application of our algorithm, the largest proportion of cases were nonspecific dementia (41.2%), followed by individuals with antidementia medication but no ADRD diagnosis (15.6%). Individuals with Alzheimer disease formed 10.2% of cases. Individuals with vascular dementia had the greatest burden of comorbid disease. Initial documentation of dementia occurred primarily in the office setting (35.1%). DISCUSSION: Our algorithm identified 6 dementia subtypes and three additional categories representing unique diagnostic patterns in the data. Differences and similarities between groups provided support for the approach and offered unique insight into ADRD subtype characteristics.

Comparison of vascular cognitive impairment--no dementia by multiple classification methods.

AIMS: To compare vascular cognitive impairment-no dementia (VCI-ND) using different classification methods. METHODS: We recruited 56 patients with VCI-ND between April 2012 and March 2013. We used a battery of neuropsychological tests to classify patients with VCI-ND into different subtypes based on memory and executive function as follows: cognitive screening (Mini-Mental State Examination, MMSE), memory (Auditory Verbal Learning Test, AVLT), executive/attention (Shape Trails Test, STT; Stroop Color-Word Test, SCWT; Reading the Mind in the Eyes, RME; Digit Ordering Test-A, DOT-A; Symbol Digit Modalities Test, SDMT), language (Action Naming Test, ANT; Boston Naming Test, BNT; Famous Face Test, FFT; Similarity Test, ST; Verbal Fluency Test, VFT) and visuospatial function (Complex Figure Test, CFT). RESULTS: The two groups had comparable demographic information (P>0.05). Amnestic VCI-ND (aVCI-ND) patients obtained significantly lower scores compared with individuals with nonamnestic VCI-ND (naVCI-ND) on the AVLT memory test, VFT language test and VFT-alternating executive test (P<0.05). Additionally, executive VCI-ND (eVCI-ND) patients performed significantly longer than nonexecutive VCI-ND (neVCI-ND) patients on the SCWT-C timed executive test. Finally, eVCI-ND patients obtained significantly lower scores compared with neVCI-ND patients on the RME, DOT-A and SDMT-correct executive tests and the ANT, BNT and ST language tests (P<0.05). CONCLUSION: aVCI-ND patients performed poorly compared with naVCI-ND patients in terms of executive and language functions, while eVCI-ND patients performed poorly compared with neVCI-ND patients in terms of language function.

Diagnosis of vascular cognitive impairment and its main categories.

OBJECTIVE: A review of current criteria for the diagnosis of categories related with vascular cognitive impairment, in particular the nomenclature, diagnostic criteria, and differential clinical-radiological findings. DEVELOPMENT: The criteria for the diagnosis of vascular cognitive impairment have evolved, but available criteria were designed basically for differentiating between vascular dementia and dementia due to Alzheimer disease, and for research purposes. Nevertheless, in clinical practice precise elements are required for: 1) Clinical diagnosis of dementia and mild cognitive impairment; 2) Clinical and neuroimaging criteria for identification of the various cerebrovascular lesions associated with cognitive dysfunction, and 3) A formulation of the aetiogenic-pathogenic relationship between cognitive impairment and cerebrovascular lesions. For this reason, a review was carried out on the diagnostic elements of vascular cognitive impairment categories, classification, and their most relevant characteristics. It highlights the characteristic for the diagnosis of multi-infarction dementia, strategic single infarct dementia, small vessel disease with dementia, mixed dementia, and vascular mild cognitive impairment. CONCLUSIONS: Standardisation is required, by a multidisciplinary expert team, as regards nomenclature and criteria for the diagnosis of the full spectrum associated with vascular cognitive impairment and especially for vascular dementia and its categories.

Vascular neuropathology and cognitive decline.

Cerebrovascular disease is an important cause of cognitive decline and dementia. Despite numerous epidemiological, clinical, neuroimaging and neuropathological studies, the link between cerebrovascular lesions and their impact on cognition and behavior is still a matter of debate. Cerebrovascular lesions are heterogeneous and most descriptive studies distinguish vessel wall modifications, perivascular space modifications, white matter changes, and infarcts as the main features of vascular dementia. However, to date there is still no consensual criteria for the neuropathological diagnosis of vascular or mixed dementia. The diagnosis of these conditions still relies on both clinical and neuropathological expertise.

Subtypes of dementia: a study from a memory clinic in India.

BACKGROUND: The clinical syndrome of dementia consists of several subtypes that are distinct in their etiology, clinical profile, management, and outcome. Limited specialized services are available for dementia patients in India. We report the profile of dementia subtypes from a clinic-based dementia registry in India. METHODS: Consecutive dementia patients were investigated with clinical evaluation, neuropsychological tests modified for local use, and brain imaging. RESULTS: In 347 consecutive dementia patients, Alzheimer's disease was the most common subtype of dementia (38.3%), followed by a high proportion of vascular dementia (25.4%). Frontotemporal dementia syndromes were not uncommon (18.7%). Dementia with Lewy bodies was encountered in 8.9% of the patients, and mixed dementia was found in 8.6%. The mean age of the group at presentation was 66.3 years, nearly a decade younger than in developed countries. The proportion of patients with early-onset dementia was high (49.9%). CONCLUSIONS: Our results demonstrate that the clinical profiles of dementia subtypes in a clinic population are influenced by the population's demographic profile, cardiovascular risk factor burden, sociocultural attitudes about cognitive impairment, and possibly genetic factors.

Classifying Non-Dementia and Alzheimer's Disease/Vascular Dementia Patients Using Kinematic, Time-Based, and Visuospatial Parameters: The Digital Clock Drawing Test.

BACKGROUND: Advantages of digital clock drawing metrics for dementia subtype classification needs examination. OBJECTIVE: To assess how well kinematic, time-based, and visuospatial features extracted from the digital Clock Drawing Test (dCDT) can classify a combined group of Alzheimer's disease/Vascular Dementia patients versus healthy controls (HC), and classify dementia patients with Alzheimer's disease (AD) versus vascular dementia (VaD). METHODS: Healthy, community-dwelling control participants (n = 175), patients diagnosed clinically with Alzheimer's disease (n = 29), and vascular dementia (n = 27) completed the dCDT to command and copy clock drawing conditions. Thirty-seven dCDT command and 37 copy dCDT features were extracted and used with Random Forest classification models. RESULTS: When HC participants were compared to participants with dementia, optimal area under the curve was achieved using models that combined both command and copy dCDT features (AUC = 91.52%). Similarly, when AD versus VaD participants were compared, optimal area under the curve was, achieved with models that combined both command and copy features (AUC = 76.94%). Subsequent follow-up analyses of a corpus of 10 variables of interest determined using a Gini Index found that groups could be dissociated based on kinematic, time-based, and visuospatial features. CONCLUSION: The dCDT is able to operationally define graphomotor output that cannot be measured using traditional paper and pencil test administration in older health controls and participants with dementia. These data suggest that kinematic, time-based, and visuospatial behavior obtained using the dCDT may provide additional neurocognitive biomarkers that may be able to identify and tract dementia syndromes.

Diagnostic Validity of the Smart Aging Serious Game: An Innovative Tool for Digital Phenotyping of Mild Neurocognitive Disorder.

BACKGROUND: The Smart Aging Serious Game (SASG) is an ecologically-based digital platform used in mild neurocognitive disorders. Considering the higher risk of developing dementia for mild cognitive impairment (MCI) and vascular cognitive impairment (VCI), their digital phenotyping is crucial. A new understanding of MCI and VCI aided by digital phenotyping with SASG will challenge current differential diagnosis and open the perspective of tailoring more personalized interventions. OBJECTIVE: To confirm the validity of SASG in detecting MCI from healthy controls (HC) and to evaluate its diagnostic validity in differentiating between VCI and HC. METHODS: 161 subjects (74 HC: 37 males, 75.47±2.66 mean age; 60 MCI: 26 males, 74.20±5.02; 27 VCI: 13 males, 74.22±3.43) underwent a SASG session and a neuropsychological assessment (Montreal Cognitive Assessment (MoCA), Free and Cued Selective Reminding Test, Trail Making Test). A multi-modal statistical approach was used: receiver operating characteristic (ROC) curves comparison, random forest (RF), and logistic regression (LR) analysis. RESULTS: SASG well captured the specific cognitive profiles of MCI and VCI, in line with the standard neuropsychological measures. ROC analyses revealed high diagnostic sensitivity and specificity of SASG and MoCA (AUCs > 0.800) in detecting VCI versus HC and MCI versus HC conditions. An acceptable to excellent classification accuracy was found for MCI and VCI (HC versus VCI; RF: 90%, LR: 91%. HC versus MCI; RF: 75%; LR: 87%). CONCLUSION: SASG allows the early assessment of cognitive impairment through ecological tasks and potentially in a self-administered way. These features make this platform suitable for being considered a useful digital phenotyping tool, allowing a non-invasive and valid neuropsychological evaluation, with evident implications for future digital-health trails and rehabilitation.

Behavioral and psychological symptoms associated with dementia subtype and severity.

BACKGROUND: There is a growing body of research exploring differences in behavioral and psychological symptoms of dementia (BPSD) between Alzheimer's disease (AD) and vascular dementia (VaD), yet these differences are inconsistent and it is uncertain whether this inconsistency might be due to the confounding effect of differing severities of dementia. METHODS: BPSD, measured with the Behavior Problems Check List (BPCL) and Revised Memory and Behavior Problems Check List (RMBPCL) and CDR-measured severity of dementia were examined using archival data of individuals with AD (N = 377) or VaD (including multi-infarct and other vascular causes; N = 74) presenting to a Sydney memory disorders clinic over a 20-year period. RESULTS: There was no significant difference in scores for AD and VaD patients on the BPCL or on the RMBPCL when controlling for sex and severity of dementia. However, severity of BPSD increased with increasing severity of dementia. CONCLUSIONS: BPSD severity is no different in AD and VaD at the time of initial assessment in a memory disorders clinic population of mild to moderate dementia. However, BPSD increases with severity of dementia in this group.

Alzheimer's/Vascular Spectrum Dementia: Classification in Addition to Diagnosis.

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common types of dementia. Although the combination of these disorders, called 'mixed' dementia, is recognized, the prevailing clinical and research perspective continues to consider AD and VaD as independent disorders. A review of recent neuropathological and neuropsychological literature reveals that these two disorders frequently co-occur and so-called 'pure' AD or VaD is comparatively rare. In addition, recent research shows that vascular dysfunction not only potentiates AD pathology, but that pathological changes in AD may subsequently induce vascular disorders. On the basis of these data, we propose that the neurobiological underpinnings underlying AD/VaD dementia and their neuropsychological phenotypes are best understood as existing along a clinical/pathological continuum or spectrum. We further propose that in conjunction with current diagnostic criteria, statistical modeling techniques using neuropsychological test performance should be leveraged to construct a system to classify AD/VaD spectrum dementia in order to test hypotheses regarding how mechanisms related to AD and VaD pathology interact and influence each other.

[Antidementia drugs]. / Antidementiva.

The pharmacological treatment of dementias aims to improve cognitive deficits, activities of daily living and behavioural and psychiatric symptoms. The weighting of theses therapeutic aims varies with disease progression. Behavioural symptoms may dominate especially in the more severe stages of the disease and may further deteriorate global functional level of the patient. Today there is no causal therapy for Alzheimer's disease (AD). Based on preclinical disease models novel therapeutic approaches are under development that target the beta-amyloid and tau protein metabolism. Some of them aim to inhibit the formation, aggregation and toxicity of beta-amyloid peptides or promote their clearance from the brain. Others inhibit the formation of neurofibrillary tangles or have neuroprotective effects. Active or passive immunisation against beta-amyloid may be a very specific and effective approach. The efficacy of acetylcholine esterase inhibitors (AchEI) in the treatment of mild to moderate AD is well documented. They are first line therapeutics in the treatment of the disease and lead to a delay of symptomatic progression. Memantine is effective in the treatment of moderate to severe stages of AD. The evidence for the treatment of vascular dementia is comparatively weak. However, positive effects have been shown for all available AchEI and memantine. Non pharmacological therapy is an indispensable part of the treatment of dementia patients and should be adapted to the individual needs of the patient in the respective stage of the disease. The efficacy of antipsychotics in the treatment of behavioural and psychiatric symptoms of dementia is limited. These drugs are associated with increased morbidity and mortality in dementia patients. Therefore, their application should be based on a critical and individual evaluation of risks and benefits.

Biomarkers identify the Binswanger type of vascular cognitive impairment.

Binswanger's disease is a form of subcortical ischemic vascular disease (SIVD-BD) with extensive white matter changes. To test the hypothesis that biomarkers could improve classification of SIVD-BD, we recruited 62 vascular cognitive impairment and dementia (VCID) patients. Multimodal biomarkers were collected at entry into the study based on clinical and neuropsychological testing, multimodal magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis. The patients' diagnoses were confirmed by long-term follow-up, and they formed a "training set" to test classification methods, including (1) subcortical ischemic vascular disease score (SIVDS), (2) exploratory factor analysis (EFA), (3) logistic regression (LR), and (4) random forest (RF). A subsequently recruited cohort of 43 VCID patients with provisional diagnoses were used as a "test" set to calculate the probability of SIVD-BD based on biomarkers obtained at entry. We found that N-acetylaspartate (NAA) on proton magnetic resonance spectroscopy (1H-MRS) was the best variable for classification, followed by matrix metalloproteinase-2 in CSF and blood-brain barrier permeability on MRI. Both LR and RF performed better in diagnosing SIVD-BD than either EFA or SIVDS. Two-year follow-up of provisional diagnosis patients confirmed the accuracy of statistically derived classifications. We propose that biomarker-based classification methods could diagnose SIVD-BD patients earlier, facilitating clinical trials.

Differences in neuropsychiatric symptoms according to mild cognitive impairment subtypes in the community.

BACKGROUND/AIMS: Mild cognitive impairment (MCI) has been subtyped according to its cognitive features and its likely etiology. We aimed to investigate the neuropsychiatric features of the MCI using the Neuropsychiatric Inventory and compare them according to subtypes. METHODS: MCI patients were classified according to cognitive features (e.g. amnestic vs. nonamnestic MCI), likely etiology (e.g. vascular vs. nonvascular MCI) and functional status (e.g. MCI-I vs. MCI-II). The percentage of subjects exhibiting each of the 12 behaviors in the Neuropsychiatric Inventory was compared among the groups using a chi(2) test. RESULTS: There were 382 subjects in the MCI group. In terms of each neuropsychiatric symptom, there were no differences in frequency between the MCI groups subtyped according to cognitive features or likely etiology. However, a significantly higher frequency of delusion, aggression, irritability and eating behavior was observed in the MCI-II group in comparison to the MCI-I group. CONCLUSION: The differences in neuropsychiatric symptoms were distinctive between the MCI groups subtyped according to functional status.

Multi-Parametric Classification of Vascular Cognitive Impairment and Dementia: The Impact of Diverse Cerebrovascular Injury Biomarkers.

Vascular cognitive impairment and dementia (VCID) is a diagnostic term applied to cognitively impaired individuals with heterogeneous cerebrovascular conditions affecting large and/or small vessels. Individual biomarkers have been identified as instrumental in relating VCID to specific underlying pathologies to better characterize this syndrome. Emerging research to refine panels of biomarkers will increase classification sensitivity and specificity. Refined VCID clustering based on the severity and pathology of vascular injury will permit the development of optimal prevention and treatment strategies. Here, we review recently reported data concerning the diversity of VCID-related pathology and attempts for VCID clustering based on biomarkers obtained from different sets of measurements. We discuss three major sets of biomarkers: 1) neuroimaging biomarkers, 2) neuropsychological performance measures, and 3) biochemical markers in current VCID clustering. Finally, we highlight the effect of blood-brain barrier health on cerebrovascular disease trajectory.

[Vascular dementia].

Vascular dementia comprises a heterogeneous group of conditions covering a range of clinical and neuropathological presentations of cerebrovascular disease-causing dementia. Vascular dementia is a common occurrence, but many questions regarding the disease remain unanswered. Recently, proposed criteria focus on constructing an overarching disease concept, which captures both pre-dementia stages and the clinical and neuropathological heterogeneity. Future research should focus on identifying subtypes with distinct pathophysiological mechanisms in order to facilitate treatment development.

A clinicopathological approach to the diagnosis of dementia.

The most definitive classification systems for dementia are based on the underlying pathology which, in turn, is categorized largely according to the observed accumulation of abnormal protein aggregates in neurons and glia. These aggregates perturb molecular processes, cellular functions and, ultimately, cell survival, with ensuing disruption of large-scale neural networks subserving cognitive, behavioural and sensorimotor functions. The functional domains affected and the evolution of deficits in these domains over time serve as footprints that the clinician can trace back with various levels of certainty to the underlying neuropathology. The process of phenotyping and syndromic classification has substantially improved over decades of careful clinicopathological correlation, and through the discovery of in vivo biomarkers of disease. Here, we present an overview of the salient features of the most common dementia subtypes - Alzheimer disease, vascular dementia, frontotemporal dementia and related syndromes, Lewy body dementias, and prion diseases - with an emphasis on neuropathology, relevant epidemiology, risk factors, and signature signs and symptoms.

Psychiatric disease in the twenty-first century: The case for subcortical ischemic depression.

The current approach to psychiatric diagnoses involves identifying symptom clusters that fit a specific syndrome. Although this approach has facilitated the field's development, advances in genetics and neuroimaging raise the question of how causality may fit into the diagnostic process. One approach would be a two-axial system, wherein clinical presentation is on one axis and putative risk factors are on the other. This approach applies to subcortical ischemic depression (SID), a diagnosis corresponding to the "vascular depression" hypothesis. Subcortical ischemic depression affects clinical presentation, long-term outcomes, and response to antidepressant therapy, arguing that it is a valid diagnostic entity worth further study.

Clinical and radiographic subtypes of vascular cognitive impairment in a clinic-based cohort study.

BACKGROUND AND PURPOSE: There is a need for empirical studies to define criteria for vascular cognitive impairment (VCI) subtypes. In this paper, we report the predictive validity of a subtype classification scheme based on clinical and radiographic features. METHODS: Nine Canadian memory clinics participated in the Consortium to Investigate Vascular Impairment of Cognition. This cohort consisted of 1347 patients, of whom 324 had VCI, and was followed for up to 30 months. RESULTS: Clinical and neuroimaging features defined three subtypes: vascular cognitive impairment, no dementia, (n=97), vascular dementia (n=101) and mixed neurodegenerative/vascular dementia (n=126). Any ischemic lesion on neuroimaging increased the odds (odds ratio=9.31; 95% confidence interval 6.46, 13.39) of a VCI diagnosis. No VCI subtype, however, was associated with a specific neuroimaging abnormality. Compared to those with no cognitive impairment, patients with each VCI subtype had higher rates of death and institutionalization (hazard ratio for combined adverse events=6.08, p<0.001). CONCLUSIONS: Both clinical features and radiographic features help establish a diagnosis of VCI. The outcomes of VCI subtypes, however, are more strongly associated with clinical features than with radiographic ones.