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Neurology Mar 2020To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and meta-analysis on AD subtype studies based on postmortem and neuroimaging data.
METHODS
EMBASE, PubMed, and Web of Science databases were consulted until July 2019.
RESULTS
Neuropathology and neuroimaging studies have consistently identified 3 subtypes of AD based on the distribution of tau-related pathology and regional brain atrophy: typical, limbic-predominant, and hippocampal-sparing AD. A fourth subtype, minimal atrophy AD, has been identified in several neuroimaging studies. Typical AD displays tau-related pathology and atrophy both in hippocampus and association cortex and has a pooled frequency of 55%. Limbic-predominant, hippocampal-sparing, and minimal atrophy AD had a pooled frequency of 21%, 17%, and 15%, respectively. Between-subtype differences were found in age at onset, age at assessment, sex distribution, years of education, global cognitive status, disease duration, APOE ε4 genotype, and CSF biomarker levels.
CONCLUSION
We identified 2 core dimensions of heterogeneity: typicality and severity. We propose that these 2 dimensions determine individuals' belonging to one of the AD subtypes based on the combination of protective factors, risk factors, and concomitant non-AD brain pathologies. This model is envisioned to aid with framing hypotheses, study design, interpretation of results, and understanding mechanisms in future subtype studies. Our model can be used along the A/T/N classification scheme for AD biomarkers. Unraveling the heterogeneity within AD is critical for implementing precision medicine approaches and for ultimately developing successful disease-modifying drugs for AD.
Topics: Alzheimer Disease; Humans
PubMed: 32047067
DOI: 10.1212/WNL.0000000000009058 -
Continuum (Minneapolis, Minn.) Apr 2016This article discusses the recent advances in the diagnosis and treatment of Alzheimer disease (AD). (Review)
Review
PURPOSE OF REVIEW
This article discusses the recent advances in the diagnosis and treatment of Alzheimer disease (AD).
RECENT FINDINGS
In recent years, significant advances have been made in the fields of genetics, neuroimaging, clinical diagnosis, and staging of AD. One of the most important recent advances in AD is our ability to visualize amyloid pathology in the living human brain. The newly revised criteria for diagnosis of AD dementia embrace the use for biomarkers as supportive evidence for the underlying pathology. Guidelines for the responsible use of amyloid positron emission tomography (PET) have been developed, and the clinical and economic implications of amyloid PET imaging are actively being explored.
SUMMARY
Our improved understanding of the clinical onset, progression, neuroimaging, pathologic features, genetics, and other risk factors for AD impacts the approaches to clinical diagnosis and future therapeutic interventions.
Topics: Alzheimer Disease; Cognition Disorders; Disease Progression; Humans; Neuropsychological Tests; Psychiatric Status Rating Scales
PubMed: 27042902
DOI: 10.1212/CON.0000000000000307 -
Current Biology : CB Jun 2018The German psychiatrist and neuropathologist Alois Alzheimer was fascinated by the symptoms of Auguste D., a 50-year-old woman admitted to the Frankfurt Psychiatric...
The German psychiatrist and neuropathologist Alois Alzheimer was fascinated by the symptoms of Auguste D., a 50-year-old woman admitted to the Frankfurt Psychiatric Hospital in 1901 who suffered from memory disturbances, paranoia and progressive confusion. After her death and autopsy, Alzheimer described histological alterations in her brain that later came to be known as amyloid plaques and neurofibrillary tangles (Figure 1). The case report was published in a psychiatric textbook some years later, and this peculiar and (at the time) seemingly rare illness was later named Alzheimer's disease.
Topics: Alzheimer Disease; Brain; Humans; Plaque, Amyloid; Risk Factors
PubMed: 29870699
DOI: 10.1016/j.cub.2018.04.080 -
Dementia and Geriatric Cognitive... 2020Alzheimer disease (AD), the most common form of dementia, is a heterogenous disorder with various pathobiological subtypes. In addition to the 4 major subtypes based on... (Review)
Review
Alzheimer disease (AD), the most common form of dementia, is a heterogenous disorder with various pathobiological subtypes. In addition to the 4 major subtypes based on the distribution of tau pathology and brain atrophy (typical, limbic predominant, hippocampal sparing, and minimal atrophy [MA]), several other clinical variants showing distinct regional patterns of tau burden have been identified: nonamnestic, corticobasal syndromal, primary progressive aphasia, posterior cortical atrophy, behavioral/dysexecutive, and mild dementia variants. Among the subtypes, differences were found in age at onset, sex distribution, cognitive status, disease duration, APOE genotype, and biomarker levels. The patterns of key network destructions parallel the tau and atrophy patterns of the AD subgroups essentially. Interruption of key networks, in particular the default-mode network that is responsible for cognitive decline, is consistent in hetero-genous AD groups. AD pathology is often associated with co-pathologies: cerebrovascular lesions, Lewy pathology, and TDP-43 proteinopathies. These mixed pathologies essentially influence the clinical picture of AD and may accel-erate disease progression. Unraveling the heterogeneity among the AD spectrum entities is important for opening a window to pathogenic mechanisms affecting the brain and enabling precision medicine approaches as a basis for developing preventive and ultimately successful disease-modifying therapies for AD.
Topics: Age of Onset; Alzheimer Disease; Atrophy; Brain; Classification; Cognition; Humans; Phylogeny; Precision Medicine; tau Proteins
PubMed: 33429401
DOI: 10.1159/000508625 -
Continuum (Minneapolis, Minn.) Jun 2022Causes of health disparities in Alzheimer disease and related dementias (ADRD) in the United States are multifactorial. This article contextualizes health disparities as... (Review)
Review
PURPOSE OF REVIEW
Causes of health disparities in Alzheimer disease and related dementias (ADRD) in the United States are multifactorial. This article contextualizes health disparities as they relate to the neurodegenerative processes of ADRD.
RECENT FINDINGS
Older adults' life expectancy has increased such that a 65-year-old is expected to live 19 or more years and an 85-year-old can expect to live, on average, 6 to 7 years longer. Individuals of certain ethnoracial groups (Black, Hispanic/Latino, American Indian/Alaska Native, and Native Hawaiian/Pacific Islander) may be at a higher risk of incident ADRD compared to non-Hispanic/Latino White people. These differences in a higher risk of ADRD across ethnoracial groups persist despite no statistically significant differences in the rate of cognitive decline over time. The intersectionality of social determinants of health, experiences with discrimination and oppression, and access to care are related to the issue of justice and the risk for and expression of ADRD. The theoretical frameworks of various health disparities provide organized approaches to tracking the progression of health disparities for diverse patients.
SUMMARY
ADRD health disparities are complex. Neurologists and their care teams must consider the main reasons for clinical ADRD evaluations of members of ethnoracial groups and the factors that may impact patient adherence and compliance with diagnostic and management recommendations.
Topics: Aged; Alzheimer Disease; Humans; United States
PubMed: 35678407
DOI: 10.1212/CON.0000000000001088 -
Nature Reviews. Neurology May 2022Alzheimer disease and related dementias present considerable challenges to health-care and medical systems worldwide. In the USA, older Black and Latino individuals are... (Review)
Review
Alzheimer disease and related dementias present considerable challenges to health-care and medical systems worldwide. In the USA, older Black and Latino individuals are more likely than older white individuals to have Alzheimer disease and related dementias. In this Perspective, we leverage our experience and expertise with older US Latino groups to review and discuss the need to integrate cultural factors into dementia research and care. We examine the importance of considering the effects of cultural factors on clinical presentation and diagnosis, dementia risk, clinical research and recruitment, and caregiving practices, with a focus on minoritized groups in the USA. We highlight critical gaps in the literature to stimulate future research aimed at improving the prevention and early detection of Alzheimer disease and related dementias and developing novel treatments and interventions across ethnoracially diverse populations. In addition, we briefly discuss some of our own initiatives to promote research and clinical care among Latino populations living in the USA.
Topics: Alzheimer Disease; Hispanic or Latino; Humans
PubMed: 35260817
DOI: 10.1038/s41582-022-00630-z -
Ugeskrift For Laeger Mar 2017Alzheimer's disease is a neurodegenerative disorder with insidious onset and slow progression. Prevalence is increasing, although not as fast as previously believed. The... (Review)
Review
Alzheimer's disease is a neurodegenerative disorder with insidious onset and slow progression. Prevalence is increasing, although not as fast as previously believed. The clinical diagnosis may be difficult, but diagnostic methods have been introduced and proven to be accurate in supporting the clinical diagnosis. Application of these methods increases, partly due to improved awareness of cognitive symptoms and the relevance of early detection and diagnosis, in particular when more efficient disease-modifying drugs become available. Currently, only symptomatic treatment can be prescribed, and focus should be on potential prophylactic strategies.
Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Excitatory Amino Acid Antagonists; Humans; Memantine; Risk Factors
PubMed: 28330540
DOI: No ID Found -
Neurotherapeutics : the Journal of the... Jan 2022As the prevalence of dementia and Alzheimer's disease (AD) increases worldwide, it is imperative to reflect on the major clinical trials in the prevention of dementia... (Review)
Review
As the prevalence of dementia and Alzheimer's disease (AD) increases worldwide, it is imperative to reflect on the major clinical trials in the prevention of dementia and the challenges that surround them. The pharmaceutical industry has focused on developing drugs that primarily affect the Aβ cascade and tau proteinopathy, while academics have focused on repurposed therapeutics and multi-domain interventions for prevention studies. This paper highlights significant primary, secondary, and tertiary prevention trials for dementia and AD, overall design, methods, and systematic issues to better understand the current landscape of prevention trials. We included 32 pharmacologic intervention trials and 9 multi-domain trials. Fourteen could be considered primary prevention, and 18 secondary or tertiary prevention trials. Major categories were Aβ vaccines, Aβ antibodies, tau antibodies, anti-inflammatories, sex hormones, and Ginkgo biloba extract. The 9 multi-domain studies mainly focused on lifestyle modifications such as blood pressure management, socialization, and physical activity. The lack of validated drug targets, and the complexity of the diagnostic frameworks, eligibility criteria, and outcome measurements for trials, make it difficult to show efficacy for both pharmacological and multi-domain interventions. We hope that this summative analysis of trials will stimulate discussion for scientists and clinicians interested in reviewing and developing preventative interventions for AD.
Topics: Alzheimer Disease; Anti-Inflammatory Agents; Exercise; Humans; Life Style; Research Design
PubMed: 35587314
DOI: 10.1007/s13311-022-01236-5 -
The Tohoku Journal of Experimental... Aug 1990Neurotransmitters including acetylcholine, dopamine, norepinephrine, serotonin, GABA and vasopressin were examined in control subjects and patients with Alzheimer-type... (Comparative Study)
Comparative Study Review
Neurotransmitters including acetylcholine, dopamine, norepinephrine, serotonin, GABA and vasopressin were examined in control subjects and patients with Alzheimer-type dementia, involving presenile and senile dementia. Neurotransmitters exhibited various mode of changes with aging. Abnormalities found in senile or presenile dementia were not always parallel to the age-related changes. These results suggest that Alzheimer-type dementia cannot be understood as an accelerated senescence, but other etiological factors might be introduced for the manifestation of the dementia. Moreover, the disturbance in neurotransmitters revealed a difference between presenile Alzheimer's disease and senile dementia, indicating that further studies should be carried out taking the age of onset into consideration.
Topics: Acetylcholinesterase; Alzheimer Disease; Arginine Vasopressin; Biopterins; Brain Chemistry; Cerebral Cortex; Choline O-Acetyltransferase; Cross-Sectional Studies; Dementia; Dopamine beta-Hydroxylase; Glutamate Decarboxylase; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Japan; Neurotransmitter Agents
PubMed: 1707190
DOI: 10.1620/tjem.161.supplement_49 -
Mayo Clinic Proceedings Jun 2017Alzheimer disease (AD) was originally conceived as a rare disease that caused presenile dementia but has come to be understood as the most prevalent cause of dementia at... (Review)
Review
Alzheimer disease (AD) was originally conceived as a rare disease that caused presenile dementia but has come to be understood as the most prevalent cause of dementia at any age worldwide. It has an extended preclinical phase characterized by sequential changes in imaging and cerebrospinal fluid biomarkers with subtle memory decline beginning more than a decade before the emergence of symptomatic memory loss heralding the beginning of the mild cognitive impairment stage. The apolipoprotein E ε4 allele is a prevalent and potent risk factor for AD that has facilitated research into its preclinical phase. Cerebral Aβ levels build from preclinical through early dementia stages followed by hyperphosphorylated tau-related pathology, the latter driving cognitive deficits and dementia severity. Structural and molecular imaging can now recapitulate the neuropathology of AD antemortem. Autosomal dominant forms of early-onset familial AD gave rise to the amyloid hypothesis of AD, which, in turn, has led to therapeutic trials of immunotherapy designed to clear cerebral amyloid, but to date results have been disappointing. Genome-wide association studies have identified multiple additional risk factors, but to date none have yielded an effective alternate therapeutic target. Current and future trials aimed at presymptomatic individuals either harboring cerebral amyloid or at genetically high risk offer the hope that earlier intervention might yet succeed where trials in patients with established dementia have failed. A major looming challenge will be that of expensive, incompletely effective disease-modifying therapy: who and when to treat, and how to pay for it.
Topics: Aging; Alzheimer Disease; Apolipoproteins E; Brain; Humans; Magnetic Resonance Imaging
PubMed: 28578785
DOI: 10.1016/j.mayocp.2017.02.011