Atypical Forms Of Alzheimer's Disease Research Articles

Potential Cardiologic Protective Effects of Acetylcholinesterase Inhibitors in Patients With Mild to Moderate Dementia

In patients with mild to moderate dementia, acetylcholinesterase inhibitors (AChE-I) are used to improve cognitive functions, but bradycardia, conduction abnormalities, and hypotension are possible side effects because of the peripheral muscarinic M2 receptor stimulation. This study aimed to evaluate the main cardiologic clinical outcomes in patients with dementia who are on AChE-I. In this retrospective, monocentric, observational cohort study, 2 groups were considered: (1) patients with dementia because of the typical and atypical forms of Alzheimer disease treated with AChE-I and (2) cognitively unimpaired, matched control group. The primary end point was a composite of cardiovascular death, nonfatal acute myocardial infarction, myocardial revascularization, occurrence of stroke and/or transient ischemic attacks, and hospitalization for heart failure occurring during a mean of 3.1years of follow-up. The secondary end points were each individual component of the primary end point, total mortality, noncardiovascular death, and incidence of pacemaker implant. Each group included 221 patients who were homogeneous in terms of age, gender, and main cardiovascular risk factors. Major adverse cardiovascular events occurred in 24 patients with dementia (2.1 per 100 patient-years) compared with 56 in control group (5.0 per 100 patient-years), p=0.036. Even if not significant, the difference was mainly driven by myocardial revascularization (3.2% vs 6.8%) and hospitalization for heart failure (4.5% vs 14.5%). As expected, noncardiovascular mortality was significantly higher in the treatment group (13.6% vs 2.7% p=0.006). No significant difference between the groups was observed in terms of other secondary outcomes. In conclusion, in patients with dementia, the use of AChE-I may be protective for cardiovascular outcomes, especially in reducing heart failure hospitalization and myocardial revascularization.

Chapter 25 - The temporal lobe in typical and atypical Alzheimer disease

Alzheimer disease (AD) is defined neuropathologically by abnormal extra-cellular β-amyloid plaques combined with intraneuronal tau aggregation. Patients sharing the same neuropathological features but presenting different clinical manifestations and evolutions have led to the notion of AD spectrum. This spectrum encompasses typical and atypical forms of AD. For all of them, specific parts of the temporal lobes, as well as their structural and functional connections with other brain regions, are affected. In typical amnestic late-onset Alzheimer's disease (>65 years old; LOAD), tau pathology gradually spreads to the brain from the medial temporal lobe (MTL). MTL is an inhomogeneous structure consisting of several subregions densely connected to each other and to other cortical and subcortical brain regions. These regions play a crucial role in the storage of information in episodic memory. In less common early-onset AD (<65 years old; EOAD), a large proportion of patients presents atypical clinical manifestations, in which memory impairment is not inaugural and predominant. Instead, these patients have predominant and/or isolated deficits in language, visuospatial, motor, or executive/behavioral functions. In atypical variants, brain damage is mainly centered on the posterior regions, with relative sparing of the MTL. However, the temporal lobe also appears to be variably and specifically damaged in some subtypes of EOAD. For example, the left superior temporal gyrus is the core of brain damage in the language variant, as well as the ventral regions of the temporal lobe play an important role in the clinic of the visual variant.

BRIDGING THE GAP BETWEEN NEUROLOGY AND PSYCHIATRY-ATYPICAL PRESENTATION OF COMMON NEURODEGENERATIVE DISORDERS: Session 418

It is increasingly recognized that there is significant heterogeneity in phenotype and clinical trajectories both in Alzheimer's as well as in Parkinson's disease. Up to 25% of Alzheimer's disease (AD) cases do not show the typical neuropathology. Recently subtypes and atypical non-amnestic AD presentations have been formalized in the International Working Group (IWG) clinical diagnosis criteria. Clinical diagnosis of atypical AD has significantly been improved by the availability of biomarkers, including cerebrospinal fluid levels of Aβ42, total tau (t-tau) and phosphorylated tau181 (p-tau), MRI volumetric estimation of hippocampal and medial temporal atrophy, and amyloid brain PET imaging. We will review the typical and atypical forms of AD from these varied perspectives to help improve diagnostic confidence among clinicians. Special attention will be given to language variant of Alzheimer's disease. A predominant deficit in the language domain is a key feature of primary progressive aphasia but language impairment is commonly present in Alzheimer's disease. International diagnostic criteria for PPA and its three variants (agrammatic, logopenic, semantic) were published relatively recently in 2011. Since then, studies have investigated the validity of these criteria in classifying patients which includes clinical symptoms, neurocognitive presentations, distinct MRI signatures, and neuropathological differences. In this session, we will review the subtypes of PPA using the above parameters to assist clinicians in diagnosis of these conditions. Special attention will be given of logopenic PPA a syndrome frequently seen in atypical Alzheimer's disease. Another common neurodegenerative disorder, Parkinson's disease (PD) conceptualized as predominantly movement disorder presents with myriad of atypical features predominantly psychiatric in nature. Psychosis is one of the most debilitating symptoms of PD, as it is an independent risk factor for nursing home placements, increased caregiver distress and mortality. Visual hallucinations are the most common psychotic manifestation in PD. Auditory, olfactory, tactile and gustatory hallucinations are infrequently found and usually coexist with visual ones. Delusions occur in about 5% of Parkinson's disease patients. Cognitive correlates of hallucinations and delusions appear to be different in PD. They may have distinct pathogenic mechanisms and possibly anatomical substrates. Global cognitive deficits including attention, frontal executive dysfunction, visuospatial abnormalities, language and verbal memory were associated with the presence of hallucinations in Parkinson's disease, but did not correlate with the presence of delusions. APOE and glucocerebrosidase gene (GBA) mutations and polymorphisms found to be associated with a distinct cognitive profile of changes characterized by greater impairment in working memory/executive function and visuospatial abilities in PD patients. During this session new findings on pathognomonic, cognitive and genetic correlates of psychosis in PD will be presented.

Posterior Cortical Atrophy.

This article presents an overview of the clinical syndrome of posterior cortical atrophy (PCA), including its pathologic underpinnings, clinical presentation, investigation findings, diagnostic criteria, and management. PCA is usually an atypical form of Alzheimer disease with relatively young age at onset. New diagnostic criteria allow patients to be diagnosed on a syndromic basis as having a primary visual (pure) form or more complex (plus) form of PCA and, when possible, on a disease-specific basis using biomarkers or underlying pathology. Imaging techniques have demonstrated that some pathologic processes are concordant (atrophy, hypometabolism, tau deposition) with clinical symptoms and some are discordant (widespread amyloid deposition). International efforts are under way to establish the genetic underpinnings of this typically sporadic form of Alzheimer disease. In the absence of specific disease-modifying therapies, a number of practical suggestions can be offered to patients and their families to facilitate reading and activities of daily living, promote independence, and improve quality of life SUMMARY: While rare, PCA is an important diagnostic entity for neurologists, ophthalmologists, and optometrists to recognize to allow for early accurate diagnosis and appropriate patient management. PCA provides an important opportunity to investigate the causes of selective vulnerability in Alzheimer disease.

Amyloid PET in neurodegenerative diseases with dementia.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aβ1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18F-FDG PET and temporal atrophy on MRI). Recently specific recommendations have been created as a consensus statement on the appropriate use of the imaging biomarkers, including amyloid PET: early-onset cognitive impairment/dementia, atypical forms of AD, mild cognitive impairment with early age of onset, and to differentiate between AD and other neurodegenerative diseases that occur with dementia. Amyloid PET is also contributing to the development of new therapies for AD, as well as in research studies for the study of other neurodegenerative diseases that occur with dementia where the deposition of Aβ amyloid is involved in its pathogenesis. In this paper, we review some general concepts and study the use of amyloid PET in depth and its relationship with neurodegenerative diseases and other diagnostic techniques.

Amyloid PET in neurodegenerative diseases with dementia

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aβ1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18F-FDG PET and temporal atrophy on MRI). Recently specific recommendations have been created as a consensus statement on the appropriate use of the imaging biomarkers, including amyloid PET: early-onset cognitive impairment/dementia, atypical forms of AD, mild cognitive impairment with early age of onset, and to differentiate between AD and other neurodegenerative diseases that occur with dementia. Amyloid PET is also contributing to the development of new therapies for AD, as well as in research studies for the study of other neurodegenerative diseases that occur with dementia where the deposition of Aβ amyloid is involved in its pathogenesis. In this paper, we review some general concepts and study the use of amyloid PET in depth and its relationship with neurodegenerative diseases and other diagnostic techniques.

Olfactory and Imaging Features in Atypical Alzheimer's Disease.

ObjectivesCognition and speech disorders are the most common symptoms of dementia in neurodegenerative disease. Here, we present a detailed clinical evaluation of a case of logopenic variant of primary progressive aphasia (lv-PPA), an atypical form of Alzheimer disease (AD), including cognitive testing over time, brain imaging, electrophysiology, and tests of olfactory function.Case reportWe present the case of a 58-year-old man suffering from progressive language difficulties who was finally diagnosed with lv-PPA. Clinical data included neuropsychological examinations, electrophysiology tests, neuroimaging, biomarkers, olfactory tests, and olfactory functional magnetic resonance imaging (fMRI).Results and DiscussionThe patient suffered from language disorders, including stumbling speech and forgetting appropriate words and how to pronounce some words. This had started 2 years earlier, and he had begun to deteriorate in recent months. In addition to his speech disorder, scores on the Mini Mental State Examination and Montreal cognitive assessment indicated that his cognition was affected. Structural imaging revealed no obvious hippocampal atrophy (score of 1), and molecular imaging showed hypometabolism and amyloid deposits in the temporal parietal region. The patient also presented with olfactory impairment. Although his odour detection threshold was normal, his cognitive threshold for scent recognition was significantly increased. Olfactory fMRI showed that activation of the whole brain and primary olfactory cortex was rare.ConclusionThis case provides evidence suggesting that lv-PPA is an atypical form of AD, with symptoms including speech disorders and impaired cognition. This patient with lv-PPA presented with olfactory impairment.

Predicting Regional Pattern of Longitudinal β-Amyloid Accumulation by Baseline PET.

Knowledge about spatial and temporal patterns of β-amyloid (Aβ) accumulation is essential for understanding Alzheimer disease (AD) and for design of antiamyloid drug trials. Here, we tested whether the regional pattern of longitudinal Aβ accumulation can be predicted by baseline amyloid PET. Methods: Baseline and 2-y follow-up 18F-florbetapir PET data from 58 patients with incipient and manifest dementia due to AD were analyzed. With the determination of how fast amyloid deposits in a given region relative to the whole-brain gray matter, a pseudotemporal accumulation rate for each region was calculated. The actual accumulation rate of 18F-florbetapir was calculated from follow-up data. Results: Pseudotemporal measurements from baseline PET data explained 87% (P < 0.001) of the variance in longitudinal accumulation rate across 62 regions. The method accurately predicted the top 10 fast and slow accumulating regions. Conclusion: Pseudotemporal analysis of baseline PET images is capable of predicting the regional pattern of longitudinal Aβ accumulation in AD at a group level. This approach may be useful in exploring spatial patterns of Aβ accumulation in other amyloid-associated disorders such as Lewy body disease and atypical forms of AD. In addition, the method allows identification of brain regions with a high accumulation rate of Aβ, which are of particular interest for antiamyloid clinical trials.