Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in 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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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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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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Working Memory and Executive Function Decline across Normal Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

BioMed Research International ◽

10.1155/2015/748212 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 137

Author(s):

Anna-Mariya Kirova ◽

Rebecca B. Bays ◽

Sarita Lagalwar

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Working Memory ◽

Cognitive Impairment ◽

Executive Function ◽

Mild Cognitive Impairment ◽

Executive Dysfunction ◽

Normal Aging ◽

Future Research ◽

Neurological Differences

Alzheimer’s disease (AD) is a progressive neurodegenerative disease marked by deficits in episodic memory, working memory (WM), and executive function. Examples of executive dysfunction in AD include poor selective and divided attention, failed inhibition of interfering stimuli, and poor manipulation skills. Although episodic deficits during disease progression have been widely studied and are the benchmark of a probable AD diagnosis, more recent research has investigated WM and executive function decline during mild cognitive impairment (MCI), also referred to as the preclinical stage of AD. MCI is a critical period during which cognitive restructuring and neuroplasticity such as compensation still occur; therefore, cognitive therapies could have a beneficial effect on decreasing the likelihood of AD progression during MCI. Monitoring performance on working memory and executive function tasks to track cognitive function may signal progression from normal cognition to MCI to AD. The present review tracks WM decline through normal aging, MCI, and AD to highlight the behavioral and neurological differences that distinguish these three stages in an effort to guide future research on MCI diagnosis, cognitive therapy, and AD prevention.

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O4-01-05: Genetic variants in 14q chromosomal region are associated with memory in late-onset Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2009.05.517 ◽

2009 ◽

Vol 5 (4S_Part_5) ◽

pp. P150-P150

Author(s):

Sandra Barral ◽

Joseph H. Lee ◽

Rong Cheng ◽

Christiane Reitz ◽

Vincent Santana ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Genetic Variants ◽

Chromosomal Region ◽

Late Onset ◽

With Memory

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Association of butyrylcholinesterase K variant with cholinesterase-positive neuritic plaques in the temporal cortex in late-onset Alzheimer's disease

Human Genetics ◽

10.1007/s004390000277 ◽

2000 ◽

Vol 106 (4) ◽

pp. 447-452 ◽

Cited By ~ 38

Author(s):

Donald J. Lehmann ◽

Zsuzsanna Nagy ◽

Suzanne Litchfield ◽

Mario Cortina Borja ◽

A. David Smith

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Late Onset ◽

Temporal Cortex ◽

Neuritic Plaques ◽

K Variant

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

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.041 ◽

2012 ◽

Vol 8 (4S_Part_1) ◽

pp. P14-P14

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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Alzheimer’s Disease-Related Metabolic Pattern in Diverse Forms of Neurodegenerative Diseases

Diagnostics ◽

10.3390/diagnostics11112023 ◽

2021 ◽

Vol 11 (11) ◽

pp. 2023

Author(s):

Angus Lau ◽

Iman Beheshti ◽

Mandana Modirrousta ◽

Tiffany A. Kolesar ◽

Andrew L. Goertzen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Lewy Bodies ◽

Future Research ◽

Metabolic Pattern ◽

Dementia Patients ◽

Positron Emission ◽

Psychological Dysfunction ◽

Underlying Causes ◽

Neuroimaging Biomarkers

Dementia is broadly characterized by cognitive and psychological dysfunction that significantly impairs daily functioning. Dementia has many causes including Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). Detection and differential diagnosis in the early stages of dementia remains challenging. Fueled by AD Neuroimaging Initiatives (ADNI) (Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. As such, the investigators within ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report.), a number of neuroimaging biomarkers for AD have been proposed, yet it remains to be seen whether these markers are also sensitive to other types of dementia. We assessed AD-related metabolic patterns in 27 patients with diverse forms of dementia (five had probable/possible AD while others had atypical cases) and 20 non-demented individuals. All participants had positron emission tomography (PET) scans on file. We used a pre-trained machine learning-based AD designation (MAD) framework to investigate the AD-related metabolic pattern among the participants under study. The MAD algorithm showed a sensitivity of 0.67 and specificity of 0.90 for distinguishing dementia patients from non-dementia participants. A total of 18/27 dementia patients and 2/20 non-dementia patients were identified as having AD-like patterns of metabolism. These results highlight that many underlying causes of dementia have similar hypometabolic pattern as AD and this similarity is an interesting avenue for future research.

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Choroidal Proteins Involved in Cerebrospinal Fluid Production may be Potential Drug Targets for Alzheimer's Disease Therapy

Perspectives in Medicinal Chemistry ◽

10.4137/pmc.s6509 ◽

2011 ◽

Vol 5 ◽

pp. PMC.S6509 ◽

Cited By ~ 5

Author(s):

Peter Wostyn ◽

Kurt Audenaert ◽

Peter Paul De Deyn

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Late Onset ◽

Future Research ◽

Caffeine Consumption ◽

Research Attention ◽

Fluid Production ◽

Β Amyloid

Alzheimer's disease is known to be the most common form of dementia in the elderly. It is clinically characterized by impairment of cognitive functions, as well as changes in personality, behavioral disturbances and an impaired ability to perform activities of daily living. To date, there are no effective ways to cure or reverse the disease. Genetic studies of early-onset familial Alzheimer's disease cases revealed causative mutations in the genes encoding β-amyloid precursor protein and the γ-secretase-complex components presenilin-1 and presenilin-2, supporting an important role of β-amyloid in the pathogenesis of Alzheimer's disease. Compromised function of the choroid plexus and defective cerebrospinal fluid production and turnover, with diminished clearance of β-amyloid, may play an important role in late-onset forms of Alzheimer's disease. If reduced cerebrospinal fluid turnover is a risk factor for Alzheimer's disease, then therapeutic strategies to improve cerebrospinal fluid flow are reasonable. However, the role of deficient cerebrospinal fluid dynamics in Alzheimer's disease and the relevance of choroidal proteins as potential therapeutic targets to enhance cerebrospinal fluid turnover have received relatively little research attention. In this paper, we discuss several choroidal proteins, such as Na+-K+ ATPase, carbonic anhydrase, and aquaporin 1, that may be targets for pharmacological up-regulation of cerebrospinal fluid formation. The search for potentially beneficial drugs useful to ameliorate Alzheimer's disease by facilitating cerebrospinal fluid production and turnover may be an important area for future research. However, the ultimate utility of such modulators in the management of Alzheimer's disease remains to be determined. Here, we hypothesize that caffeine, the most commonly used psychoactive drug in the world, may be an attractive therapeutic candidate for treatment of Alzheimer's disease since long-term caffeine consumption may augment cerebrospinal fluid production. Other potential mechanisms of cognitive protection by caffeine have been suggested by recent studies.

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