scholarly journals Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE): Clinical and Neuropathological Associations

2019 ◽  
Vol 79 (3) ◽  
pp. 305-313 ◽  
Author(s):  
Lilah M Besser ◽  
Merilee A Teylan ◽  
Peter T Nelson
Keyword(s):  
Hippocampal Sclerosis ◽  
Temporal Cortex ◽  
Lewy Body Disease ◽  
Inferior Temporal Cortex ◽  
Common Disease ◽  
Predominant Symptom ◽  
Age Related ◽  
Motor Problems ◽  
Potential Risk Factors ◽  
Immunohistochemical Studies

Abstract Recently, a consensus working group provided new terminology for a common disease entity, limbic predominant age-related TDP-43 encephalopathy (LATE), and its neuropathological substrate (LATE-NC). LATE-NC not only often co-occurs with Alzheimer disease neuropathological change (ADNC), but also may present in isolation. The present study aimed to investigate potential risk factors and neuropathological characteristics associated with LATE-NC. A sample of 616 autopsied participants (>75 years at death), with TDP-43 immunohistochemical studies performed, was obtained from the National Alzheimer’s Coordinating Center. Logistic regression analyses examined associations between demographic, clinical and neuropathological characteristics and LATE-NC (TDP-43 in amygdala, hippocampus, or entorhinal/inferior temporal cortex) (alpha = 0.05). Adjusted models indicated that ADNC, hippocampal sclerosis (HS), arteriolosclerosis, and limbic or amygdala-predominant Lewy body disease (LBD), but not other LBD subtypes, were associated with higher odds of LATE-NC, whereas congestive heart failure (CHF) and motor problems as first predominant symptom were associated with lower odds of LATE-NC. Our findings corroborate previous studies indicating associations between LATE-NC and ADNC, HS, and arteriolosclerosis. Novel findings suggest the association with LATE-NC is restricted to amygdala/limbic-predominant subtype of LBD, and a possible protective (or competing risk) association with CHF. This study may inform future hypothesis-driven research on LATE-NC, a common brain disease of aging.

scholarly journals Risk factors of hippocampal sclerosis in the oldest old

Neurology ◽  
2018 ◽  
Vol 91 (19) ◽  
pp. e1788-e1798 ◽  
Author(s):  
Thomas Trieu ◽  
Seyed Ahmad Sajjadi ◽  
Claudia H. Kawas ◽  
Peter T. Nelson ◽  
María M. Corrada
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Thyroid Disease ◽  
Hippocampal Sclerosis ◽  
Oldest Old ◽  
Lewy Body Disease ◽  
Thyroid Stimulating Hormone ◽  
Autoimmune Conditions ◽  
Potential Risk Factors ◽  
History Of

ObjectiveTo examine the risk factors and comorbidities of hippocampal sclerosis (HS) in the oldest-old.MethodsA total of 134 participants with dementia from The 90+ Study with longitudinal evaluations and autopsy were included in this investigation. Participants were divided into 2 groups, one with and one without HS pathology, and differences in clinical and pathologic characteristics were compared.ResultsPersons with HS tended to have a longer duration of dementia compared to participants without HS (mean 4.0 years vs 6.7 years, odds ratio [OR] 1.26; 95% confidence interval [CI] 1.11–1.42; p < 0.001). HS was more likely in participants with a history of autoimmune diseases (rheumatoid arthritis or thyroid disease, OR 3.15; 95% CI 1.30–7.62; p = 0.011), high thyroid-stimulating hormone (OR 4.94; 95% CI 1.40–17.46; p = 0.013), or high thyroid antibodies (OR 3.45; 95% CI 1.09–10.88; p = 0.035). Lewy body disease (LBD) pathology was also associated with an increased likelihood of HS (OR 5.70; 95% CI 1.22–26.4; p = 0.027).ConclusionWe identified autoimmune conditions (rheumatoid arthritis and thyroid disease) as potential risk factors for HS in our cohort. LBD was the only pathology that was associated with increased odds of HS and those harboring HS pathology had a longer duration of dementia. This suggests multiple pathways of HS pathology among the oldest-old.

scholarly journals Hippocampal Sclerosis in Older Patients: Practical Examples and Guidance With a Focus on Cerebral Age-Related TDP-43 With Sclerosis

2017 ◽  
Vol 141 (8) ◽  
pp. 1113-1126 ◽  
Author(s):  
Matthew D. Cykowski ◽  
Suzanne Z. Powell ◽  
Paul E. Schulz ◽  
Hidehiro Takei ◽  
Andreana L. Rivera ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Alzheimer Disease ◽  
Frontotemporal Lobar Degeneration ◽  
Late Onset ◽  
Hippocampal Sclerosis ◽  
Oldest Old ◽  
Significant Proportion ◽  
Lewy Body Disease ◽  
Older Population ◽  
Age Related

Context.— Autopsy studies of the older population (≥65 years of age), and particularly of the “oldest-old” (≥85 years of age), have identified a significant proportion (∼20%) of cognitively impaired patients in which hippocampal sclerosis is the major substrate of an amnestic syndrome. Hippocampal sclerosis may also be comorbid with frontotemporal lobar degeneration, Alzheimer disease, and Lewy body disease. Until recently, the terms hippocampal sclerosis of aging or hippocampal sclerosis dementia were applied in this context. Recent discoveries have prompted a conceptual expansion of hippocampal sclerosis of aging because (1) cellular inclusions of TAR DNA-binding protein 43 kDa (TDP-43) are frequent; (2) TDP-43 pathology may be found outside hippocampus; and (3) brain arteriolosclerosis is a common, possibly pathogenic, component. Objective.— To aid pathologists with recent recommendations for diagnoses of common neuropathologies in older persons, particularly hippocampal sclerosis, and highlight the recent shift in diagnostic terminology from HS-aging to cerebral age-related TDP-43 with sclerosis (CARTS). Data Sources.— Peer-reviewed literature and 5 autopsy examples that illustrate common age-related neuropathologies, including CARTS, and emphasize the importance of distinguishing CARTS from late-onset frontotemporal lobar degeneration with TDP-43 pathology and from advanced Alzheimer disease with TDP-43 pathology. Conclusions.— In advanced old age, the substrates of cognitive impairment are often multifactorial. This article demonstrates common and frequently comorbid neuropathologic substrates of cognitive impairment in the older population, including CARTS, to aid those practicing in this area of pathology.

scholarly journals Alzheimer's Disease Including Focal Presentations

2019 ◽  
Vol 39 (02) ◽  
pp. 213-226 ◽  
Author(s):  
Nicolas Villain ◽  
Bruno Dubois
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Chronic Traumatic Encephalopathy ◽  
Hippocampal Sclerosis ◽  
Clinical Status ◽  
Lewy Body Disease ◽  
Epidemiological Data ◽  
Cortical Atrophy ◽  
Age Related

AbstractAlzheimer's disease (AD) is the commonest neurodegenerative disease and the most frequent cause of dementia. It affects 30 million people worldwide. Current research criteria focus on biomarkers' status for amyloid and tau using positron emission tomography and cerebrospinal fluid analysis, independent of clinical status. Current epidemiological data, which mostly rely on biomarker-undetermined AD cases, have highlighted ApoE4 and age as the main risk factors. Rare autosomal dominant mutations also account for a small fraction of early-onset AD. The main clinical phenotype at presentation is the amnestic phenotype targeting episodic memory. This is followed by rarer phenotypes such as posterior cortical atrophy, logopenic variant of primary progressive aphasia, frontal variant AD, corticobasal syndrome, and other even rarer presentations mimicking language variants of frontotemporal dementia. Main differential diagnoses include hippocampal sclerosis with TDP-43, primary age-related tauopathy, argyrophilic grain disease, frontotemporal lobar degeneration, Lewy body disease, chronic traumatic encephalopathy as well as nondegenerative disorders such as cerebrovascular disease, chronic alcohol consumption, limbic encephalitis, medial temporal lobe epilepsy, and others. Co-occurrence of AD pathology with other neurodegenerative and vascular diseases is common and increases with age. This presents a challenge in current clinical practice due to a lack of reliable biomarkers for non-AD neurodegenerative diseases.

scholarly journals Comorbid neuropathological diagnoses in early vs late-onset Alzheimer’s disease

2020 ◽  
Author(s):  
Salvatore Spina ◽  
Renaud La Joie ◽  
Cathrine Petersen ◽  
Amber L. Nolan ◽  
Deion Cuevas ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Late Onset ◽  
Clinical Phenotype ◽  
Hippocampal Sclerosis ◽  
Lewy Body Disease ◽  
Pathological Diagnosis ◽  
Amyloid Angiopathy ◽  
Clinical Dementia Rating ◽  
Age Related ◽  
E4 Allele

AbstractCopathologies play an important role in the expression of the AD clinical phenotype and may influence treatment efficacy. Early-onset AD (EOAD), defined as manifesting before age 65, has been viewed as a relatively pure form of AD with a more homogenous neuropathological substrate. We sought to compare the frequency of common neuropathological diagnoses in a consecutive autopsy series of 96 patients with EOAD (median age of onset = 55 years, 44 females) and 48 with late-onset AD (LOAD) (median age of onset = 73 years, 14 females). The UCSF Neurodegenerative Disease Brain Bank database was reviewed to identify patients with a primary pathological diagnosis of AD. Prevalence and stage of Lewy body disease (LBD), limbic age-related TDP-43 encephalopathy (LATE), argyrophilic grain disease (AGD), hippocampal sclerosis (HS), cerebral amyloid angiopathy (CAA), vascular brain injury (VBI) and aging-related tau astrogliopathy (ARTAG) were compared between the two cohorts. We found at least one non-AD pathological diagnosis in 98% of patients with EOAD (versus 100% of LOAD), and the number of comorbid diagnoses per patient was lower in EOAD than in LOAD (median=2 versus 3, Mann-Whitney Z=3.00, p=0.002). LBD and CAA were common in both EOAD and LOAD (CAA: 86% versus 79%, Fisher exact p=0.33; LBD: 49% versus 42%, p=0.48, respectively), although amygdala-predominant LBD was more commonly found in EOAD than LOAD (22% versus 6%, p=0.02). In contrast, LATE (35% versus 8%, p<0.001), HS (15% versus 3%, p=0.02), AGD (58% versus 41%, p=0.052), and VBI (65% versus 39%, p=0.004) were more common in LOAD than EOAD, respectively. The number of copathologies predicted worse cognitive performance at the time of death on MMSE (1.4 points/pathology (95%CI [−2.5, −0.2]) and Clinical Dementia Rating – Sum of Boxes (1.15 point/pathology, 95%CI [0.45, 1.84]), across the EOAD and the LOAD cohorts. Prevalence of at least one ApoE e4 allele was similar across the two cohorts (52%) and was associated with a greater number of copathologies (+0.42, 95%CI [0.01, 0.82], p=0.04), independent of age of symptom onset. Our findings suggest that non-AD pathological diagnoses play an important role in the clinical phenotype of EOAD with potentially significant implications for clinical practice and clinical trials design.

scholarly journals Development of the P300 from childhood to adulthood: a multimodal EEG and MRI study

2018 ◽  
Author(s):  
Knut Overbye ◽  
Rene J. Huster ◽  
Kristine B. Walhovd ◽  
Anders M. Fjell ◽  
Christian K. Tamnes
Keyword(s):  
Surface Area ◽  
Temporal Cortex ◽  
Relevant Information ◽  
Inferior Temporal Cortex ◽  
Cross Sectional ◽  
Attentional Processes ◽  
Age Related ◽  
Brain Responses ◽  
Component Strength ◽  
Mri Study

ABSTRACTMaturation of attentional processes is central to cognitive development. The electrophysiological P300 is associated with rapid allocation of attention, and bridges stimulus and response processing. P300 is among the most studied and robust electrophysiological components, but how different subcomponents of the P300 develop from childhood to adulthood and relate to structural properties of the cerebral cortex is not well understood. We investigated age-related differences in both early visual and P300 components, and how individual differences in these components related to cortical structure in a cross-sectional sample of participants 8-19 years (n=86). Participants completed a three-stimulus visual oddball task while high-density EEG was recorded. Cortical surface area and thickness were estimated from T1-weighthed MRI. Group-level blind source separation of the EEG data identified two P300-like components, a fronto-central P300 and a parietal P300, as well as a component reflecting N1 and P2. Differences in activity across age were found for the parietal P300, N1 and P2, with the parietal P300 showing stronger activity for older participants, while N1 and P2 were stronger for younger participants. Stronger P300 components were positively associated with task performance, independently of age, while negative associations were found for P2 strength. Parietal P300 strength was age-independently associated with larger surface area in a region in left lateral inferior temporal cortex. We suggest that the age differences in component strength reflect development of attentional mechanisms, with increased brain responses to task-relevant stimuli representing an increasing ability to focus on relevant information and to respond accurately and efficiently.

Dementia in the Forensic Setting: Diagnoses Obtained Using a Condensed Protocol at the Office of Chief Medical Examiner, New York City

2021 ◽  
Author(s):  
David S Priemer ◽  
Rebecca D Folkerth
Keyword(s):  
New York ◽  
New York City ◽  
Cerebrovascular Disease ◽  
York City ◽  
Hippocampal Sclerosis ◽  
Lewy Body Disease ◽  
High Rate ◽  
Medical Examiner ◽  
Age Related ◽  
Jakob Disease

Abstract Individuals with dementia may come to forensic autopsy, partly because of non-natural deaths (e.g. fall-related), and/or concerns of abuse/neglect. At the New York City Office of Chief Medical Examiner (NYC OCME), brains from such cases are submitted for neurodegenerative disease (ND) work-up. Seventy-eight sequential cases were evaluated using a recently published condensed protocol for the NIA-AA guidelines for the neuropathologic assessment of Alzheimer disease (AD), a cost-cutting innovation in diagnostic neuropathology. ND was identified in 74 (94.9%) brains; the most common were AD (n = 41 [52.5%]), primary age-related tauopathy (n = 26 [33.3%]), and Lewy body disease ([LBD], n = 25 [32.1%]). Others included age-related tau astrogliopathy, hippocampal sclerosis of aging, progressive supranuclear palsy, multiple system atrophy, amyotrophic lateral sclerosis, argyrophilic grain disease, and Creutzfeldt-Jakob disease. 26.8% of AD cases involved a non-natural, dementia-related death, versus 40.0% for LBD. Finally, 70 (89.7%) cases had chronic cerebrovascular disease, 53 (67.9%) being moderate-to-severe. We present a diverse distribution of NDs notable for a high rate of diagnoses associated with falls (e.g. LBD), a potential difference from the hospital neuropathology experience. We also report a high burden of cerebrovascular disease in demented individuals seen at the NYC OCME. Finally, we demonstrate that the aforementioned condensed protocol is applicable for a variety of ND diagnoses.

scholarly journals Name Calling in the Temporal Lobe

2008 ◽  
Vol 8 (6) ◽  
pp. 156-158
Author(s):  
Warren T. Blume ◽  
Brent Hayman-Abello
Keyword(s):  
Temporal Lobe ◽  
Posterior Distribution ◽  
Hippocampal Sclerosis ◽  
Temporal Cortex ◽  
Cortical Reorganization ◽  
Inferior Temporal Cortex ◽  
Temporal Region ◽  
Lexical Information ◽  
Temporal Lobe Resection

Evidence for Cortical Reorganization of Language in Patients with Hippocampal Sclerosis. Hamberger MJ, Seidel WT, Goodman RR, Williams A, Perrine K, Devinsky O, McKhann GM 2nd. Brain 2007;130(Pt 11):2942–2950. Naming is mediated by perisylvian cortex in the left (language-dominant) hemisphere, and thus, left anterior temporal lobe resection for pharmacologically intractable temporal lobe epilepsy (TLE) carries risk for post-operative naming decline. Interestingly, this risk is lower in patients with hippocampal sclerosis (HS) relative to those without HS (non-HS). Although the hippocampus has traditionally been considered a critical structure for memory, without contribution to naming, this pattern might implicate direct hippocampal naming involvement. On the other hand, critical naming sites have been found in anterior, lateral temporal (i.e. extra-hippocampal) neocortex, the region typically removed with ‘standard’ TLE resection. We, therefore, speculated that the relative preservation of naming in post-operative HS patients might reflect cortical reorganization of language to areas outside this region. Using pre-resection electrical stimulation mapping, we compared the topography of auditory and visual naming sites in 12 patients with HS and 12 patients without structural brain pathology. Consistent with previous work, non-HS patients exhibited post-operative naming decline, whereas HS patients did not. As hypothesized, HS patients had proportionally fewer overall naming sites in anterior temporal cortex, the region typically removed with standard anterior temporal resection, whereas non-HS patients exhibited a more even distribution of naming sites in anterior and posterior temporal regions ( P = 0.03). Although both groups exhibited the previously reported pattern of auditory naming sites anterior to visual naming sites, auditory naming sites had a significantly more posterior distribution in HS patients ( P = 0.02). Additionally, non-HS patients exhibited a greater proportion of visual naming sites above the superior temporal sulcus, whereas visual naming sites in HS patients were scattered across superior and inferior temporal cortex. Results suggest that preserved naming ability in HS patients following anterior temporal resection might be attributable, at least in part, to intrahemispheric reorganization of language in response to the likely, early development of sclerosis in the medial temporal region. Furthermore, their more posterior distribution of naming sites is consistent with the more anterior propagation of EEG discharges in TLE. These results hold theoretical implications regarding the role of the dominant hippocampus in determining the cortical representation of semantic and lexical information, and raise questions regarding the specific roles of medial and lateral temporal cortex in targeted word retrieval. The different patterns of naming areas identified in patients with and without HS may also carry clinical implications, potentially improving efficiency during the time-constrained process of stimulation mapping.

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