The Latest in Alzheimer’s Disease Research: Bruno Giordani, PhD Associate Director, Michigan Alzheimer [s Disease enter Senior Director, Mary A. Rackham Institute Professor, Psychiatry, Neurology, Psychology, and School of Nursing oard Member and Past hair, Michigan Great Lakes hapter, Alzheimer [s Association Aug 25, · It is well known that dementia is associated with increased mortality. New scientific research shows how in recent years more deaths are being registered with dementia as the underlying cause of death. The growth in the rate of dementia related deaths may be connected to an increased awareness about dementia as a fatal disease Aug 31, · A Research Paper on Alzheimer’s Disease. In this paper, I will be giving an overview of Alzheimer’s disease. This will include its history, prognosis and treatment available and recent advancements made towards finding a cure. Alzheimer’s disease is a somewhat recently discovered phenomenon
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Try out PMC Labs and tell us what you think. Learn More. Although dementia has been described in ancient texts over many centuries e. Alzheimer published his now famous case study only years ago, and our modern understanding of the disease that bears his name, and its neuropsychological consequences, really only began to accelerate in the s. During the s our field began its foundational studies of profiling the neuropsychological deficits associated with AD and its differentiation from other dementias e.
subcortical dementias. The s continued these efforts and began to identify the specific cognitive mechanisms affected by various neuropathologic substrates. The s ushered in a focus on the study of prodromal stages of neurodegenerative disease before the full-blown dementia syndrome i. The current decade has seen the rise of imaging and other biomarkers to characterize preclinical disease before the development of significant cognitive decline.
Finally, we suggest future directions and predictions for dementia-related research and potential therapeutic interventions. One of the great challenges faced by neuropsychologists over the past 50 years is to understand the cognitive and behavioral manifestations of dementia and their relationship to underlying brain pathology. This challenge has grown substantially over the years with the aging of the population and the age-related nature of many dementia-producing neurodegenerative diseases.
Although the concept of dementia has existed for thousands of years Mahandra, research papers alzheimers recent,it is only early in the past century that the essential clinical syndrome and associated neurodegenerative changes were first discovered. If objects are shown to her, she names them correctly, but almost immediately afterwards she has forgotten everything. When reading a test, she skips from line to line or reads by spelling the words individually, or by making them meaningless through her pronunciation, research papers alzheimers recent.
In writing she repeats separate syllables many times, research papers alzheimers recent, omits others and quickly breaks down completely. Plainly, research papers alzheimers recent, she does not understand certain questions.
She does not remember the use of some objects. When Auguste Deter died, Alzheimer used the then-new silver staining histological technique to examine her brain microscopically. When he did so, he observed the neuritic plaques, neurofibrillary tangles, and amyloid angiopathy that were to become the hallmarks of the disease that now bears his name as shown in Figure 2 from sketches of the histologic preparations in his paper. This classification was essentially adopted by the American Psychiatric Association APA to define dementia in the first two editions of their Diagnostic and Statistical Manual of Mental Disorders DSM.
This was the first study to strongly link the clinical features of AD with the pathologic brain changes that Alzheimer had described Figure 3. Neuropsychological studies of dementia and AD during this period were rare and largely limited to presenile dementia with onset before the age of A notable exception was a series of studies by Edgar Miller who showed that the main behavioral feature research papers alzheimers recent presenile AD is a memory disorder in which recently acquired information fails to reach long-term memory storage due research papers alzheimers recent both an abnormally research papers alzheimers recent loss of material from short-term storage perhaps due to encoding inefficiency and difficulty in transferring information between short-term and long-term storage systems Miller, He also suggested that inefficient retrieval of information from long-term storage may contribute to the memory deficit in presenile AD Miller, A major sea-change in the study of dementia occurred in when Robert Katzman summarized data showing that senile and presenile AD were histopathologically identical and suggested that, based on epidemiological data, AD was the fourth leading cause of death in the elderly Katzman, Suddenly, AD dementia went from a relatively rare condition to a major public health issue.
At this time, research papers alzheimers recent, the diagnostic criteria for dementia were refined in the DSM-III American Psychiatric Association, and International Statistical Classification of Diseases and Related Health Problems, 10th Revision World Health Organization,and specific research diagnostic criteria for AD were established McKhann et al. Also notable at this time was a growing realization that various dementing disorders are associated with patterns of relatively preserved and impaired cognitive abilities that vary depending upon the etiology and neuropathology of the underlying disease.
This pattern of impairment was contrasted with the cortical dementia e. The new criteria for dementia and AD adopted in the s improved the reliability of the clinical diagnosis and allowed group studies of mildly demented patients to be carried out with a reasonable degree of accuracy.
Many of these studies applied the theories and methods of cognitive psychology to study the cognitive consequences of AD. By using this approach, these studies characterized the component cognitive processes underlying the neuropsychological deficits observed in AD, and showed that cognitive changes attributable to AD and other dementing disorders could have important implications for existing theories of brain—behavior relationships underlying normal cognition.
Several studies at this time showed that episodic memory impairment i. These findings were consistent with neuropathologic studies that showed extensive AD pathology occurs earliest in medial temporal lobe MTL structures e, research papers alzheimers recent.
Research papers alzheimers recent memory deficit was shown to reflect an inability to effectively encode and store new information since patients with very early AD were particularly impaired on measures of delayed recall i, research papers alzheimers recent. In addition, patients with AD more often produced intrusion errors i. This pattern of memory deficits was shown to differ from the pattern exhibited by patients with subcortical dementia who had difficulty learning new information, but retained what was learned well and showed improved performance with retrieval aids e.
These findings provided evidence of differential roles of MTL and fronto-striatal brain structures in memory performance. Studies also showed that, as the neuropathology of AD spreads beyond MTL structures to adjacent temporal, parietal, and frontal association cortices, several higher order cognitive abilities became affected. A deficit in language abilities i. Patients were highly consistent in the individual items they missed across different semantic memory tests that used unique modes of access and output e, research papers alzheimers recent.
These findings demonstrated that AD results in a true loss of semantic knowledge i. A similar loss of knowledge was thought to contribute to the severe deficit patients with AD exhibited in the ability to remember past events that were successfully remembered before the onset of the disease i. Executive dysfunction and deficits in attention played a less prominent role in the AD dementia syndrome than in the subcortical dementia syndrome associated with fronto-striatal dysfunction.
Visuospatial tasks that were sensitive to early AD often involved not only visuoperceptual and constructional aspects of performance, but also required conceptual knowledge e.
The advances made in characterizing the neuropsychological deficits associated with AD had a major impact on the ability to accurately diagnose the disease in its early stages. This clinical utility was demonstrated in a study that compared the ability of several sensitive measures of learning and memory, executive abilities, language, and visuospatial abilities to differentiate between mild AD and matched normal control subjects Salmon et al.
This study also illustrated that the pattern of cognitive deficits typically associated with AD is characterized by prominent deficits in episodic and semantic memory, with additional, although somewhat less prominent, deficits in executive functions, visuospatial abilities, and attention. Receiver research papers alzheimers recent characteristic curves demonstrating excellent sensitivity and specificity for the accurate diagnosis of early AD achieved with neuropsychological tests of memory California Verbal Learning Testlanguage category fluency: animals, fruits, and vegetables and executive functions Trail-Making Test: Part B adapted from Salmon et al.
There are, however, somewhat rare instances, particularly in younger patients e. These patients had a significantly higher burden of neurofibrillary tangles, but not neuritic plaques, in the frontal cortex than a matched group of patients with a typical clinical presentation of AD. A subset of patients with primary progressive aphasia PPA was found to have AD pathology. These patients usually presented with logopenic PPA PPA-Lwhich is characterized by hesitant, grammatically correct speech and spared language comprehension Gorno-Tempini et al.
PPA-L is most often associated with AD pathology disproportionately distributed in language-related cortical areas Mesulam et al. However, considerable work has been done to identify how the neuropsychological presentations of these disorders differs from that of typical AD, and this information has been incorporated into the most recent clinical diagnostic criteria for behavioral variant FTLD Rascovsky et al.
During the s and early s, important advances were also made in identifying genetic risks for AD. Mutations on three separate genes were identified in large families that displayed an autosomal dominant inheritance pattern of an early-onset form of AD i.
A far more common genetic risk factor for sporadic, late-onset AD was identified as the type ε4 allele of the gene for apolipoprotein E APOEresearch papers alzheimers recent, a low density lipoprotein cholesterol carrier Strittmatter et al.
The performance of non-demented older adults who have an increased risk for developing the disease due to an APOE ε4 genotype could be compared research papers alzheimers recent that of individuals who do not have this risk factor with the presumption that more individuals with the ε4 genotype are in a preclinical stage of the disease. In one such study, Bondi, Salmon, Galasko, Thomas, and Thal compared the neuropsychological test performances of non-demented elderly individuals with or without at least one APOE ε4 allele.
Cox proportional hazards analysis showed that APOE ε4 status and measures of delayed recall were significant independent predictors of subsequent progression to AD, suggesting that poor recall is an early sensitive neuropsychological marker of AD and not a cognitive phenotype of the ε4 genotype also see Bondi et al. Although in the s a few investigators had begun to systematically study individuals at risk for dementia to determine whether cognitive declines could be detected before diagnosis Bondi et al.
MCI was defined as a condition in which individuals experience memory loss to a greater extent than one would expect for age, yet do not meet criteria for dementia.
The specific clinical criteria for MCI they originally put forth were: 1 subjective memory complaint, 2 objective memory impairment for age, 3 relatively preserved general cognition, 4 essentially intact activities of daily living, and 5 not demented Petersen et al.
With the advent of these new criteria, the study of MCI became widespread during the s. To illustrate this increasing attention and productivity, Petersen and colleagues noted that in fewer than 50 papers were published in the medical literature on the topic of MCI, whereas bythis number approached peer-reviewed studies in that year alone see Figure 5. He rightly concluded that the increased awareness and study of MCI had been extremely valuable for the field by enhancing our understanding of the early neuropsychological manifestations of AD and improving the ability to identify those at risk for progression to dementia, research papers alzheimers recent.
Note the exponential rate of increase in the numbers of publications during the s research papers alzheimers recent Petersen et al. Research papers alzheimers recent and characterization of prodromal AD continued to be a vibrant area of research moving into the s.
The new guidelines for MCI largely retained the criteria developed by Petersen and colleagues, research papers alzheimers recent, but expanded the subjective cognitive complaint criterion to allow the complaint to come from either the patient, an informant or a skilled clinician, and incorporated the use of biomarkers into the diagnosis research papers alzheimers recent below.
Research began on the potential of subjective cognitive complaints alone to accurately signal the development of underlying AD pathology for review, see Jessen et al. Although the criteria for MCI have been widely adopted, recent research has demonstrated limitations in the way the criteria were operationalized for research papers alzheimers recent trials e. These studies operationalized MCI as subjective complaints about memory, normal performance on simple cognitive screens, marginal memory ratings on scales based on clinical judgment, and impaired performance on a single memory test.
Unfortunately, this method appears to be highly susceptible to false positive diagnostic errors Bondi et al. This susceptibility was demonstrated by Edmonds, Delano-Wood, Clark, et al. Despite their MCI diagnosisapproximately one-third of these participants performed within normal limits on this more extensive cognitive testing and showed a low rate of progression to dementia.
Given these limitations in the conventional diagnostic criteria, Jak, Bondi, and colleagues Jak et al, research papers alzheimers recent. Rather than using a single memory test, research papers alzheimers recent, a diagnosis of MCI is established on the basis of scores achieved on multiple objective neuropsychological tests that assess a range of cognitive domains without reference to subjective complaints or clinical judgment.
This actuarial method was shown to produce greater diagnostic stability than the conventional method i. Over the past 20 years great progress was made in identifying in vivo biological markers of AD. Several investigators refined the ability to detect and measure cerebrospinal fluid levels of Aβ the main constituent of the plaque and tau protein a constituent of the neurofibrillary tangle that were indicative of AD pathology in the brain.
Klunk and colleagues see Mathis et al. All of these biomarkers have greatly increased the accuracy with which AD pathology in the brain can be detected before the onset of cognitive symptoms, and improved the ability to differentiate AD from other pathologies that lead to dementia.
In the current decade, several large-scale longitudinal studies have examined the relationship between various AD biomarkers and the development of cognitive decline and dementia e.
Based on results from these studies, Jack and colleagues research papers alzheimers recent a hypothetical model of dynamic biomarker changes in the development of AD, research papers alzheimers recent. Their model, research papers alzheimers recent, consistent with the amyloid cascade hypothesisproposed that amyloid deposition related to abnormal processing of the amyloid precursor protein i.
This in turn leads to tangle-mediated neuronal injury and neurodegeneration, which then produces cognitive and functional impairment see Jack et al. Many biomarker studies align with this temporal sequence of pathophysiologic changes, particularly in early-onset autosomal dominant mutation carriers e. The hypothesis also provided the framework for revised diagnostic criteria for AD McKhann et al. Despite its wide influence, there is increasing evidence that calls the amyloid cascade hypothesis into research papers alzheimers recent, especially with regard to its invariant temporal sequence of pathological events Drachman, Axonal injury Ryan et al.
In addition, a growing number of studies have shown that cognitive measures can be as sensitive as physical biomarkers in predicting progression to dementia Gomar et al. Taken together, these findings strongly suggest that the neurodegeneration of AD may not depend upon prior amyloidosis Knopman et al. Jack, Knopman, et al. Our prior work Edmonds, Delano-Wood, Galasko, research papers alzheimers recent, et al. We have shown that cognitively normal individuals who later progressed to MCI or AD, and had only one abnormal biomarker at baseline, were most likely to have neurodegeneration i.
In fact, research papers alzheimers recent, neurodegeneration in isolation was 2. Jack, Bennett, and colleagues have recently acknowledged these and similar findings and proposed a more descriptive classification scheme for AD biomarkers that is agnostic to the temporal ordering of mechanisms underlying AD pathogenesis.
Current Treatments and Research for Alzheimer's Disease
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Alzheimer's and dementia research – find the latest information on research funding, grants, clinical trials and global research news. Get information and resources for Alzheimer's and other dementias from the Alzheimer's Association. Call our 24 hours, seven days a The Latest in Alzheimer’s Disease Research: Bruno Giordani, PhD Associate Director, Michigan Alzheimer [s Disease enter Senior Director, Mary A. Rackham Institute Professor, Psychiatry, Neurology, Psychology, and School of Nursing oard Member and Past hair, Michigan Great Lakes hapter, Alzheimer [s Association Aug 31, · A Research Paper on Alzheimer’s Disease. In this paper, I will be giving an overview of Alzheimer’s disease. This will include its history, prognosis and treatment available and recent advancements made towards finding a cure. Alzheimer’s disease is a somewhat recently discovered phenomenon
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