IC-P-009: Different patterns of cortical atrophy in early- and late-onset Alzheimer's disease

We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer’s disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid–positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research.

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Diﬃculties in diagnosing atypical variants of Alzheimer’s disease

Russian neurological Journal ◽

10.30629/2658-7947-2021-26-5-16-23 ◽

2021 ◽

Vol 26 (5) ◽

pp. 16-23

Author(s):

A. A. Tappakhov ◽

T. Ya. Nikolaeva ◽

T. E. Popova ◽

N. A. Shnayder

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Picture ◽

Short Term Memory ◽

Late Onset ◽

Early Stage ◽

Primary Progressive Aphasia ◽

Cortical Atrophy ◽

Posterior Cortical Atrophy ◽

Short Term

Alzheimer’s disease (AD) is the most common cause of dementia in the population. Late onset AD has a classic clinical picture with short-term memory deficit, apraxia and agnosia. Patients with early-onset AD may have an atypical clinical picture which complicates diagnosis. Atypical AD variants include the logopenic variant of primary progressive aphasia, posterior cortical atrophy, behavioral, biparietal, and cortico-basal variants. These variants have pathomorphological signs similar to classical AD, but at an early stage they are characterized by focal atrophy which explains their clinical polymorphism. This article provides a review of the current literature on atypical types of AD and presents a clinical case of a 62-year-old patient in whom the disease debuted with prosopagnosia due to focal atrophy of the temporo-occipital regions of the non-dominant hemisphere.

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P1-146: Different patterns of cortical atrophy in early- and late-onset Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.423 ◽

2012 ◽

Vol 8 (4S_Part_4) ◽

pp. P157-P157

Author(s):

Christiane Möller ◽

Hugo Vrenken ◽

Lize Jiskoot ◽

Adriaan Versteeg ◽

Frederik Barkhof ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Late Onset ◽

Cortical Atrophy

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Association of Subcortical Structural Shapes With Tau, Amyloid, and Cortical Atrophy in Early-Onset and Late-Onset Alzheimer’s Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2020.563559 ◽

2020 ◽

Vol 12 ◽

Author(s):

Eun-Chong Lee ◽

Jae Myeong Kang ◽

Seongho Seo ◽

Ha-Eun Seo ◽

Sang-Yoon Lee ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Late Onset ◽

Cortical Atrophy

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Interfamilial and Intrafamilial Phenotypic Heterogeneity in Familial Alzheimer's Disease

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/089198879701000101 ◽

1997 ◽

Vol 10 (1) ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Robert F. Lopez-Alberola ◽

Warren W. Barker ◽

Dylan G. Harwood ◽

David A. Loewenstein ◽

Peter H. St. George-Hyslop ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Late Onset ◽

Phenotypic Expression ◽

Phenotypic Heterogeneity ◽

Cortical Atrophy ◽

Imaging Features ◽

Familial Alzheimer’S Disease ◽

Familial Alzheimer's Disease

The features of Alzheimer's disease (AD) are very heterogenous, and some component of the variability of AD is likely to be related to genetic factors. To investigate this question, we evaluated 19 clinical neuropsychiatric and brain imaging features in 32 familial Alzheimer's disease (FAD) kindred, primarily of late onset. Within families, patients displayed a high degree of phenotypic heterogeneity (PH), which occurred irrespective of gender, ethnicity, or apolipoprotein E genotype. Overall, an equivalent amount of PH was observed in both the between- (37%) and within-family (31%) groups. However, for onset age and rate of decline between families, there was greater PH than within families ( P = .002 and P = .01, respectively). A similar trend was found for severity of cortical atrophy ( P = .05). These observations suggest a weak genetic influence, and possibly strong nongenetic influences, on the degree of phenotypic heterogeneity in late-onset FAD. In early-onset AD kindred, a much smaller degree of phenotypic heterogeneity may be expected within families, because genetic influences in phenotypic expression tend to be more prominent in early-onset cases.

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Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer’s disease

10.1101/064295 ◽

2016 ◽

Author(s):

Xiuming Zhang ◽

Elizabeth C. Mormino ◽

Nanbo Sun ◽

Reisa A. Sperling ◽

Mert R. Sabuncu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Executive Function ◽

Bayesian Model ◽

Late Onset ◽

Temporal Cortex ◽

Cortical Atrophy ◽

Individual Level ◽

Dementia Patients ◽

With Memory

AbstractWe employed a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural magnetic resonance imaging (MRI) of late-onset Alzheimer’s disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus and amygdala), a subcortical atrophy factor (striatum, thalamus and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid-positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, while the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared to temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Code from this manuscript is publicly available at link_to_be_added.

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P3-009: Association study of late-onset Alzheimer's disease risk variants and risk for posterior cortical atrophy

Alzheimer s & Dementia ◽

10.1016/j.jalz.2013.05.1078 ◽

2013 ◽

Vol 9 ◽

pp. P553-P553

Author(s):

Minerva Carrasquillo ◽

Qurat ul Ain Khan ◽

Melissa Murray ◽

Siddharth Krishnan ◽

Thuy Nguyen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Association Study ◽

Disease Risk ◽

Late Onset ◽

Cortical Atrophy ◽

Posterior Cortical Atrophy ◽

Risk Variants

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P4-107: Genetic risk factors for posterior cortical atrophy may be distinct from late-onset Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.1810 ◽

2012 ◽

Vol 8 (4S_Part_18) ◽

pp. P669-P670 ◽

Cited By ~ 1

Author(s):

Jonathan Schott ◽

Sebastian Crutch ◽

James Uphill ◽

Natalie Ryan ◽

Tim Shakespeare ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Genetic Risk ◽

Late Onset ◽

Genetic Risk Factors ◽

Cortical Atrophy ◽

Posterior Cortical Atrophy

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Familial Patterns of Risk in Very Late-Onset Alzheimer's Disease

PsycEXTRA Dataset ◽

10.1037/e334202004-004 ◽

2003 ◽

Author(s):

J. M. Silverman ◽

C. J. Smith ◽

D. B. Marin ◽

R. C. Mohs ◽

C. B. Propper

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Late Onset ◽

Familial Patterns

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Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

Current Protein and Peptide Science ◽

10.2174/1389203721666200921152246 ◽

2020 ◽

Vol 21 (12) ◽

pp. 1164-1173

Author(s):

Siju Ellickal Narayanan ◽

Nikhila Sekhar ◽

Rajalakshmi Ganesan Rajamma ◽

Akash Marathakam ◽

Abdullah Al Mamun ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Precursor Protein ◽

Early Onset ◽

Late Onset ◽

Precursor Protein ◽

Brain Disorder ◽

Amyloid Aβ ◽

T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

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