Common Major and Mild Neurocognitive Disorders: Alzheimer Disease, Frontotemporal, Lewy Body, and Vascular Types

2018 ◽  
pp. 203-242
Author(s):  
Ana Hategan ◽  
James A. Bourgeois ◽  
Tracy Cheng ◽  
Julie Young
2017 ◽  
Author(s):  
David Knopman

There are a relatively small number of disorders that account for the majority of dementia in the elderly that is not Alzheimer disease (AD): cerebrovascular disease, Lewy body disease (α-synucleinopathies), and the frontotemporal lobar degenerations. Cerebrovascular disease and Lewy body disease account for most non-AD dementia among persons in the eighth decade of life and beyond. These two frequently co-occur with AD but can occur in their pure forms rarely (in the case of dementia associated with cerebrovascular disease) or more commonly (in the case of Lewy body disease). There is no one cognitive or behavioral syndrome associated with cerebrovascular disease; however, attempts to isolate a common theme suggest that cognitive slowing is typical of cerebrovascular contributions to cognitive impairment. Cerebrovascular pathology relevant to cognitive impairment accumulates subclinically more commonly than it causes acute, strokelike declines in cognition. Dementia with Lewy bodies is a multidimensional disorder that includes a nonamnestic dementia, Parkinson disease or at least some parkinsonian features, a disorder of sleep and wakefulness, autonomic disturbances, and depression. The disorders of sleep prominently include rapid eye movement sleep behavior disorder, excessive daytime sleepiness, visual hallucinations, and marked fluctuations in level of alertness. The frontotemporal lobar degenerations are nearly as common as causes of dementia in persons under age 65 as is AD. The group of disorders includes two cognitive syndromes (primary progressive aphasia and behavior variant frontotemporal dementia) and two neuropathologic subtypes (tauopathy and TDP43 proteinopathy) and is associated with three major autosomal dominant genetic mutations (in MAPT, GRN, and C9ORF72). Key words: dementia with Lewy bodies, frontotemporal lobar degenerations, vascular cognitive impairment


2004 ◽  
Vol 128 (1) ◽  
pp. 32-38 ◽  
Author(s):  
Catherina Fu ◽  
Dennis J. Chute ◽  
Emad S. Farag ◽  
Justine Garakian ◽  
Jeffrey L. Cummings ◽  
...  

Abstract Context.—There is a paucity of accurate postmortem data pertinent to comorbid medical conditions in patients with dementia, including Alzheimer disease. Objectives.—The purposes of this study were (a) to examine general autopsy findings in patients with a dementia syndrome and (b) to establish patterns of central nervous system comorbidity in these patients. Design.—Review of autopsy reports and selected case material from 202 demented patients who had “brain-only” autopsies during a 17-year period (1984–2000) and from 52 demented patients who had general autopsies during a 6-year period (1995–2000). Setting.—Large academic medical center performing approximately 200 autopsies per year. Results.—Among the 52 patients who underwent complete autopsy, the most common cause of death was bronchopneumonia, which was found in 24 cases (46.1%). Other respiratory problems included emphysema, found in 19 (36.5%) of 52 patients, and pulmonary thromboembolism, found in 9 (17.3%) of 52 patients. In 6 cases, pulmonary thromboembolism was the proximate cause of death. Twenty-one (40.3%) of the 52 patients had evidence of a myocardial infarct (varying ages) and 38 (73.1%) had atherosclerotic cardiovascular disease, 27 of a moderate to severe degree. Four clinically unsuspected malignancies were found: 1 each of glioblastoma multiforme, diffusely infiltrative central nervous system lymphoma, pancreatic adenocarcinoma, and adenocarcinoma of the lung. One patient with frontotemporal dementia and amyotrophic lateral sclerosis died of severe meningoencephalitis/ventriculitis, probably secondary to seeding of the central nervous system by an infected cardiac valve. Of the 202 demented patients who underwent brain-only autopsies, the following types of dementia were found: 129 (63.8%) cases showed changes of severe Alzheimer disease, 21 (10.4%) showed combined neuropathologic abnormalities (Alzheimer disease plus another type of lesion, such as significant ischemic infarcts or diffuse Lewy body disease), 12 (5.9%) cases of relatively pure ischemic vascular dementia, 13 (6.4%) cases of diffuse Lewy body disease, and 8 (4.0%) cases of frontotemporal dementia. The remaining 19 (9.4%) patients showed miscellaneous neuropathologic diagnoses, including normal pressure hydrocephalus and progressive supranuclear palsy. Among the demented patients, 92 (45.5%) had cerebral atherosclerosis, which was moderate to severe in 65 patients (32.2%). Conclusions.—Some of the conditions found at autopsy, had they been known antemortem, would likely have affected clinical management of the patients. Autopsy findings may be used as a quality-of-care measure in patients who have been hospitalized in chronic care facilities for a neurodegenerative disorder.


2020 ◽  
Vol 79 (4) ◽  
pp. 407-418
Author(s):  
Jorge A Trejo-Lopez ◽  
Zachary A Sorrentino ◽  
Cara J Riffe ◽  
Stefan Prokop ◽  
Dennis W Dickson ◽  
...  

Abstract Human neurodegenerative diseases can be characterized as disorders of protein aggregation. As a key player in cellular autophagy and the ubiquitin proteasome system, p62 may represent an effective immunohistochemical target, as well as mechanistic operator, across neurodegenerative proteinopathies. In this study, 2 novel mouse-derived monoclonal antibodies 5G3 and 2A5 raised against residues 360–380 of human p62/sequestosome-1 were characterized via immunohistochemical application upon human tissues derived from cases of C9orf72-expansion spectrum diseases, Alzheimer disease, progressive supranuclear palsy, Lewy body disease, and multiple system atrophy. 5G3 and 2A5 reliably highlighted neuronal dipeptide repeat, tau, and α-synuclein inclusions in a distribution similar to a polyclonal antibody to p62, phospho-tau antibodies 7F2 and AT8, and phospho-α-synuclein antibody 81A. However, antibodies 5G3 and 2A5 consistently stained less neuropil structures, such as tau neuropil threads and Lewy neurites, while 2A5 marked fewer glial inclusions in progressive supranuclear palsy. Both 5G3 and 2A5 revealed incidental astrocytic tau immunoreactivity in cases of Alzheimer disease and Lewy body disease with resolution superior to 7F2. Through their unique ability to highlight specific types of pathological deposits in neurodegenerative brain tissue, these novel monoclonal p62 antibodies may provide utility in both research and diagnostic efforts.


Neurology ◽  
2018 ◽  
Vol 91 (3) ◽  
pp. e268-e279 ◽  
Author(s):  
Koji Kasanuki ◽  
Keith A. Josephs ◽  
Tanis J. Ferman ◽  
Melissa E. Murray ◽  
Shunsuke Koga ◽  
...  

ObjectiveTo describe clinical and pathologic characteristics of diffuse Lewy body disease (DLBD) manifesting as corticobasal syndrome (CBS).MethodsIn 523 autopsy-confirmed cases of DLBD, we identified 11 patients diagnosed with CBS. For comparison, we studied 22 DLBD brains with antemortem presentation of dementia with Lewy bodies (DLB). Given previous studies suggesting the importance of pathology in peri-Rolandic cortices in CBS, we used digital pathology to count Lewy bodies and to quantify intracytoplasmic and neuritic α-synuclein and phospho-tau burden in the motor cortex.ResultsDLBD patients with antemortem features of CBS were significantly younger at disease onset and less likely to have REM sleep behavior disorder than DLBD cases who met clinical criteria for DLB during life. Patients with DLBD manifesting as CBS had more Lewy bodies in the motor cortex than DLBD manifesting as clinically probable DLB. Three cases had concomitant progressive supranuclear palsy and 4 cases had concomitant Alzheimer disease as probable correlates of CBS.ConclusionThe neuropathology underlying CBS is heterogeneous, including corticobasal degeneration, Alzheimer disease, and progressive supranuclear palsy. This study suggests that atypical variants of Lewy body disease with severe peri-Rolandic Lewy-related pathology can present clinically as CBS. Patients with DLBD who present as CBS tend to have an earlier age at onset and are less likely to have clinical features of DLB, such as dream enactment behavior during sleep, visual hallucinations, and levodopa-responsive parkinsonism. Future studies with biofluid or molecular imaging biomarkers for α-synuclein will permit better recognition of this uncommon pathologic substrate of CBS.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 747-747
Author(s):  
Regula Robnett ◽  
Thomas Meuser

Abstract Lucidity is the typical cognitive state of adults. However, conditions such as Alzheimer Disease and major neurocognitive disorders can rob people of their usual clarity. Episodes of “paradoxical lucidity” (PL) happen when there is a spontaneous return of lucidity in people who are assumed to have lost the capacity to engage and communicate. These often take place near the end of life. Anecdotal stories depicting PL have been shared for centuries, but the etiology and mechanisms of PL rarely have been examined scientifically. The purpose of this mixed-methods project was to “gather the stories,” of witnessed episodes of PL, to describe them, including potential triggers and contextual supports. Sixty witnesses of episodes have shared their experiences. Two-thirds those displaying PL were female. Most had died within six months of the episode. Episodes generally lasted under an hour (range: “moments” up to 5+ hours). Illustrative descriptions about PL emerged: 1) A trusted person or professional, perhaps unknowingly, saying or doing the right thing could trigger an episode; 2) PL frequently took place in a sacred environment involving ritual spiritual practices (e.g., saying the rosary and singing hymns); 3) meaningful music was often a trigger; and 4) PL sometimes involved the return of one’s professional or familial/friend role. Familiar sounds (e.g., music, voices) were the most common sensory antecedents. A deeper understanding of PL events could potentially drive interventions to promote these valued episodes. The possibility that end-stage neurocognitive impairments could be reversible, even for a short period, is thought-provoking and inspiring.


1998 ◽  
Vol 57 (10) ◽  
pp. 955-960 ◽  
Author(s):  
Daniel F. Brown ◽  
Richard C. Risser ◽  
Eileen H. Bigio ◽  
Patrick Tripp ◽  
Ashley Stiegler ◽  
...  

1995 ◽  
Vol 9 (4) ◽  
pp. 218-222 ◽  
Author(s):  
C. Strong ◽  
B. H. Anderton ◽  
R. H. Perry ◽  
E. K. Perry ◽  
P. G. Ince ◽  
...  

2006 ◽  
Vol 14 (7S_Part_9) ◽  
pp. P520-P520
Author(s):  
Jonathan Vöglein ◽  
Katrina L. Paumier ◽  
Nigel J. Cairns ◽  
Erin E. Franklin ◽  
Richard J. Perrin ◽  
...  

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