Adult Cognitive DiseaseThe research corpus Monographs
635 articles

Concepts

The connective tissue of the corpus — every idea the theses and the vault hold in common. 635 are linked from at least one page and indexed below; 0 orphan notes that nothing yet links to are pooled at the foot.

The load-bearing concepts most referenced

Concept51 refs

Autophagy
Concept43 refs

Cellular Senescence
Concept39 refs

Neuroinflammation
Concept27 refs

Oskar Fischer Founder
Concept27 refs

Reelin-ApoE receptor axis disruption
Concept23 refs

Autophagic Collapse
Concept23 refs

cognitive resilience
Concept23 refs

Lysosomal Acidification
Concept22 refs

Tau Pathology
Concept21 refs

Cholesterol Homeostasis
Concept21 refs

Mitochondrial Dysfunction
Concept21 refs

Perineuronal Nets

A 87

Abeta aggregation as necessary initiating event7 Abeta as molecular prime mover2 Abeta as physiological modulator of synaptic homeostasis3 Abeta as stress response marker4 Activated microglia imaging for treatment guidance3 Acyloxyacyl Hydrolase Neuroprotection5 AD as a double prion disorder5 AD as accelerated aging of Abeta management3 AD as accelerated normal aging3 AD as accumulation of insults exceeding homeostasis3 AD as addiction-like circuit pathology5 AD as autoimmune disorder6 AD as clinical syndrome not disease4 AD as multiple diseases3 AD as systemic disease not limited to brain3 AD caused by APP dysregulation not Abeta per se5 AD-diabetes shared mechanism3 Adrenergic Signaling15 Adult hippocampal neurogenesis restoration10 Adult Neurogenesis9 Age-dependent feedback loops in neurodegeneration6 Age-dependent threshold model3 Age-related immune dysfunction enables neurotropic viruses3 Aging accelerators and decelerators3 Aging as Mechanism3 Aging as root cause of AD4 Aging-epigenetic-genetic interaction3 AI Disease Model Discovery2 AI Neurotherapeutic Discovery6 AI-based early diagnosis4 Alpha-sheet toxicity in disease pathogenesis4 Aluminum as primary environmental cause3 Aluminum driving amyloid production7 Amyloid and tau as secondary byproducts3 Amyloid and tau as secondary phenomena3 Amyloid as age-related phenomenon4 Amyloid as antimicrobial defense6 Amyloid as compensatory mechanism4 Amyloid as defense mechanism against parasites3 Amyloid as downstream secondary3 Amyloid as innate immune defense gone awry3 Amyloid as secondary to synaptic dysfunction3 Amyloid clearance as important as deposition4 Amyloid Clinical Disconnect3 Amyloid Nucleation4 Amyloid plaques as fibrotic scar tissue from BBB repair4 Amyloid structural diversity and toxicity4 Amyloid-beta as innate immune defense4 Anti Ferroptotic Botanicals5 Anti-prion therapeutics as novel drug strategy7 Anti-TNF-alpha therapeutic strategy5 Antibody Target Specificity4 Antimicrobial Defense7 Antimicrobial hypothesis of amyloid8 Antioxidant defense failure4 ApoE isoform-heparin binding differences8 ApoE-centric unified model5 APOE4 Endolysosomal Dysfunction2 APOE4 Pathogen Interaction7 ApoE4 structural vulnerability6 APP and tau pathology linked through transport disruption4 APP as dependence receptor5 APP processing pathway3 Astrocyte network management hypothesis4 Astrocyte-centric AD hypothesis5 Astrocyte-centric AD mechanism5 Astrocyte-driven amyloid buildup4 Asymptomatic AD Phenotyping2 Atherosclerosis as AD driver3 Atherosclerotic obstruction4 ATN biomarker classification system4 ATP depletion as direct trigger of tau pathology3 ATP-chaperone-protein folding axis4 Autoimmune contribution via BBB compromise3 Autoimmune Neurodegeneration4 Autophagic Collapse23 Autophagic Flux12 Autophagy51 Autophagy Dysfunction7 Autophagy-amyloid coupling4 Autophagy-lysosomal failure5 Autophagy-metabolism crosstalk in AD3 Axon initial segment as key disease locus5 Axonal atheroma hypothesis3 Axonal Transport10 Axonal transport failure as unifying mechanism3 Ayurvedic medicine approach3

B 28

Bacterial exudate-driven neurodegeneration7 Barrier dysfunction pathology5 BBB as gatekeeper failure3 BBB breakdown cascade7 BBB degradation and pathogen invasion3 BBB-mediated vascular contribution3 BCG Immune Checkpoint Modulation7 Beta Alanine Neurotransmission4 Bimodal brain (inference vs training)4 BIN1 Autophagic Regulation8 Bioenergetic Collapse16 Bioenergetic defects as early events3 Bioenergetics11 Biogenic amines disrupt cellular translation fidelity3 Biological spintronic sensing3 Biomarker gap in neurology3 Blood-based biomarker discovery3 Blood-based biomarker panels for preclinical detection3 Blood-based lipid and protein module biomarkers5 Brain buoyancy hypothesis3 Brain DNA blueprint is altered in AD neurons5 Brain hemisphere synchronization3 Brain Immune Interface7 Brain Lipid Homeostasis Restoration5 Brain plasticity decline driving AD progression3 Brain structure-function relationships3 Brain-glucose-steal as mechanism of cognitive impairment4 Brain-heart health connection4

C 62

Ca2+-cAMP signaling convergence in neurodegeneration3 Calcium dyshomeostasis as upstream AD mechanism3 Calcium Homeostasis7 Calcium signaling disruption3 Calcium-mediated tauopathy3 Cannabinoid Neuroprotection1 Cannabis as primary environmental AD cause3 Causation pyramid model3 CD74 Microglial Signaling2 CDK3 Cell Cycle Toxicity5 Cellular Identity7 Cellular Senescence43 Cellular Vectors3 Cerebral Self-Management Process4 Childhood experience shaping AD vulnerability3 Cholesterol deficiency driving AD pathology14 Cholesterol Homeostasis21 Cholesterol Transport11 Cholinergic network failure in AD10 Cholinergic neuron vulnerability8 Cholinergic primacy in AD9 Chronic Excitatory Insufficiency16 Chronic intracellular infection model6 Chronic intracellular pathogen-driven neurodegeneration3 Chronic intranasal infection explaining slow AD progression3 Chronic mild hypothermia as AD cause3 Chronic neuroinflammation from infection3 Chronic neuroinflammation from periphery4 Chronobiologic neuroprotection via melatonin6 Circadian disruption as cause not consequence5 Circadian Immune Regulation8 Circadian regulation of glial function5 Clearance failure vs. overproduction3 Cognitive fitness as disease-modifying factor3 Cognitive reserve building7 Cognitive reserve hypothesis6 cognitive resilience23 Cognitive resilience as dynamic protective concept4 Community-based dementia support model3 Compensatory Homeostasis3 Computational AD Subtyping2 Computational disease subtyping3 Computational models of associative memory3 Continuum of senile cognitive decline6 Convergent risk factor pathways3 Convergent signaling through Wnt-PCP-RhoA-ROCK3 Convergent Synaptic Collapse11 Cortisol-driven secretase dysfunction7 Coverage Fraction5 Cranial bone compression causing brain atrophy5 CRISPR-like protein immunity model3 Critique of amyloid dogma3 Critique of mono-causal therapeutics3 Cross Disease Prion Mechanisms5 Cross-disease protein aggregation parallels3 CSF flow dynamics3 Culturally adapted dementia care3 Cumulative axonal defect accumulation4 Cumulative inflammation threshold for neurodegeneration9 Curcumin multi-target action3 Cytoskeletal disorder as core pathology5 Cytoskeletal Dynamics6

D 17

Dark Genome Variation8 Dehydration as AD risk factor3 Denervation supersensitivity4 Destructive emotions as root cause of all disease6 Dietary Fatty Acid APOE4 Rescue3 Dietary intervention as primary prevention4 Dietary neuroprotection3 Dietary neurotoxin exposure as modifiable risk factor5 Dietary Sodium Neurodegeneration6 Disease as behavioral feedback mechanism3 Disorientation vs memory loss distinction4 Dose-dependent mitochondrial dysfunction determines pathology type4 Double-hit mutation hypothesis5 Dual Pathogen AD Pathogenesis5 Dynamic and region-independent disease mechanisms6 Dynamic neural circuit failure model7 Dysregulated homeostatic units4

E 43

Early-life neuroinflammatory priming7 ECM remodeling in neurodegeneration3 Eight factors of dementia framework3 Electrochemical basis of cognitive decline3 Emotional transformation as therapeutic approach3 Endocrine-circadian-inflammation axis3 Endolysosomal Dysfunction8 Endosomal Lysosomal Network5 Endosomal Trafficking13 Energy failure as primary AD driver3 Energy failure as root cause3 Energy Metabolism6 Energy metabolism decline3 Energy metabolism failure drives neurodegeneration3 Entropy acceleration from maladaptive thinking3 Entropy as organizing principle8 Environmental and emotional risk factors3 Environmental and socioeconomic risk factors3 Environmental CxI inhibitors as AD etiological agents4 Environmental neurotoxicology3 Environmental Toxicology3 Environmental toxicology of neurodegeneration3 Environmental toxin contribution3 Environmental vs. genetic causation3 Epidemiological correlation argument3 Epigenetic and genetic interplay3 Epigenetic Regulation5 Epigenetic regulation of AD genes3 Epigenetic Repression5 Equilibrium at criticality5 ER Stress7 ESCRT III Membrane Scission6 Evolutionary biochemistry of disease3 Evolutionary framework for AD causation3 Evolutionary mismatch between genes and modern lifestyle8 Evolutionary mismatch hypothesis6 Evolutionary vulnerability of brain structures3 Excitatory Neurotransmission8 Exercise as cognitive catalyst6 Existing HIV RT inhibitors as potential AD therapeutics7 Expanded Prion Paradigm5 Exponential exposure-prevalence correlation3 Extracellular Matrix Pathology3

F 9

Factor classification and connectivity5 Familial vs sporadic AD7 Ferroptosis12 Ferroptosis as implicated pathway7 Ferroptosis in Neurodegeneration6 Ferroptosis Phase II Oligodendrocyte7 Five-factor quintet model of AD causation3 Folate-B12 therapeutic intervention3 Functional model of neuron-glia interaction3

G 27

GAG-driven AD pathogenesis3 Gene dosage of APP directly causes pathogenesis4 Gene Environment Interaction7 Genetic evidence as gold standard for causality6 Genetic shortcuts in FAD vs LOAD3 GI-tract microbiome neurotoxicity8 Glia-neuron interaction dysfunction3 Glial Biology2 Glial contribution to neurodegeneration3 Glial inflammatory response3 Glial-driven neuroinflammatory disease model3 Gliotransmitter dysregulation3 Glycobiology3 Glycolysis-fat oxidation metabolic switch9 Glymphatic Clearance6 Glymphatic clearance failure6 Glymphatic clearance failure amplifies pathology6 GlyNAC as novel nutritional therapeutic for AD3 Gravity and cerebral perfusion6 Gravity-dependent brain perfusion4 Gravity-dependent brain vulnerability4 GSH deficiency as root cause of multiple AD defects5 Gut Brain Axis6 Gut Microbiome Lipid AD Axis7 Gut-brain axis in AD3 Gut-brain axis in neuroinflammation3 Gut-brain axis via tryptamine production8

H 10

Head-down time and dementia3 Head-down time hypothesis3 Health disparities in AD3 Hippocampal hyperexcitability as pre-AD state3 Hippocampal neuron vulnerability3 Holistic multi-level therapeutic approach3 Homeostatic disruption model of AD2 Homeostatic Microglial Collapse12 Host Defense Peptides2 Human-germ interaction model6

I 35

Iatrogenic contribution via medications3 IDE-insulin-Abeta competition6 Immediate preventive interventions4 Immune Checkpoint Therapy7 Immune-pathogen interaction model6 Immunometabolic Checkpoints5 Immunometabolism7 Immunosenescence as central aging mechanism3 Inciting injury model4 Infection as co-factor in neurodegeneration3 Infection-triggered epigenetic cascade model3 Infectious etiology of AD2 Infectious etiology of late-onset AD6 Infectious etiology of LOAD3 Infectious origin of Alzheimer's disease3 Infectious-toxic-genetic synergy3 Inflamm-aging as disease driver6 Inflammaging integrates hallmarks of aging4 Information Theoretic Transcriptomics6 Innate immune function of amyloid proteins3 Innate immune-mediated plaque formation4 Innate Immunity19 Innate immunity failure in sporadic AD7 Innate immunity network dysregulation in AD3 Inside Out Plaque12 Integrated molecular-to-network perspective4 Integrative complementary therapy approach4 Integrative treatment across medical traditions4 Interconnected homeostatic disruption3 Interlinked pathological cascades3 Intracellular Amyloid9 Intraneuronal amyloid accumulation as primary event4 Iron Brain Paradox3 Iron Dyshomeostasis2 iron dyshomeostasis in AD1

K 2

Ketogenic diet as primary AD therapy4 Kinase Inhibitor Neuroprotection16

L 25

L-type CCB neuroprotective strategy5 LC Morphology What is Established4 Lifestyle and behavioral factors3 Lifestyle as causal anchor8 Lifestyle intervention for cognitive reversal3 Lifestyle intervention for neurodegeneration3 Lifestyle Microglial Modulation5 Lifestyle-based AD prevention4 Limbic brain as circavital clock locus4 Lipid Dysregulation3 Lipid homeostasis as AD driver3 Lipid Metabolism10 Lipid Peroxidation9 Lipid peroxidation cascade at synapse8 Lipid Transport8 Lipid-driven neurodegeneration3 Lipid-glycan crosstalk in AD4 Liver-brain metabolic axis3 Lock and Key memory reactivation4 Locus coeruleus as ground zero12 Long preclinical phase of AD pathology5 Longitudinal observational evidence4 Lysosomal Acidification23 Lysosomal Dysfunction18 Lysosomal Storage Disease3

M 61

Matrix Sulfation Node8 Mechanical risk factor for AD3 Meditation as neuroprotective intervention4 Membrane Biology3 Membrane Biophysics8 Membrane Lipid Dysregulation2 Membrane lipid pathology in AD3 Memory building framework4 Memory construction disease model3 Memory encoding-retrieval interference3 Meningeal T Cell Regulation6 Mercury as primary AD cause3 Metabolic dysfunction as AD driver3 Metabolic dysfunction in neurodegeneration3 Metabolic origin of amyloid and tau3 Metabolic-neurodegenerative disease axis3 Metabolic-neurodegenerative disease connection4 Metal-protein interaction in disease3 Microbial Pathogenesis5 Microbiome-immune-brain integration9 Microbleeds as initiating vascular event in AD3 Microglial cytokine storm9 Microglial dysfunction as early event3 Microglial Immunometabolism2 Microglial Lipid Regulation2 Microglial Protein Biomarkers7 Microglial senescence as AD trigger9 Micronutrient therapeutic potential4 Microtubule quantum information processing5 Mind-body causation in neurodegeneration3 Mind-body correspondence in disease formation6 Mind-body-soul integration for treatment6 miRNA as mechanistic link3 Mitochondrial Dysfunction21 Mitochondrial inheritance and AD3 Mitochondrial theory of aging4 Modifiability of AD risk6 Modifiable risk factor intervention4 Morphological analysis methodology7 Mosaic model of aging brain6 Moving brain hypothesis5 MTHFR as catalytic pre-existing factor6 Multi-cellular pathology6 Multi-factorial etiology of AD3 Multi-level heterogeneity of AD3 Multi-omics network approach to AD3 Multi-pathway AD pathophysiology review3 Multi-system medicine approach to AD3 Multi-target vs mono-target3 Multi-targeting the amyloid hypothesis3 Multidomain AD Intervention5 Multifactorial causal network3 Multifactorial convergence model3 Multifactorial etiology3 Multifactorial modulation of disease trajectory6 Multifactorial prevention through modifiable risk factors5 Multifactorial risk accumulation model3 Multipathology convergence theory3 Multiple chronic stressors3 Multiple converging factors in unified tauopathy framework3 Musical reminiscence as neurological intervention3

N 38

NAD+ depletion drives neurodegeneration3 Natural product polytherapy3 Navigable database of AD factors3 NbM as origin of sporadic AD5 Necrotic Cell Death4 Need to understand normal APP function5 Network-based combination therapy6 Network-based neurodegeneration3 Neural circuit breakdown model6 Neural Oscillations2 Neurodegeneration as aberrant development5 Neuroendocrine shift at menopause4 Neuroimmune Surveillance9 Neuroimmunology9 Neuroinflammation39 Neuroinflammation as primary driver connecting all AD subsystems3 Neuroinflammatory disequilibrium4 Neuronal activity as survival factor5 Neuronal Excitability1 Neuronal lysis forming extracellular plaques8 Neuronal maturation context in disease3 Neuronal network degradation as substrate of dementia5 Neuroplasticity-based cognitive enhancement3 Neurotransmitter disruption cascade3 Neurovascular dysfunction as initiating event9 Neurovascular injury-repair cycle driving disease progression7 Neurovascular unit as disease origin8 NF-kB-miRNA inflammatory cascade5 Non-dimensional quantum pathway3 Non-enzymatic AChE signaling5 Non-invasive thermal therapy3 Non-optimal aging rather than normal aging process3 Non-pharmacological cognitive enhancement3 Novel systems analysis approach3 Nuclear pathology as early AD mechanism6 Nutritional deficiency as AD cause5 Nutritional modulation of neuroinflammation3 Nutritional rebalancing over pharmacological intervention5

O 17

Olfactory Route Neuroinvasion5 Olfactory vector hypothesis8 Oligomer hypothesis of neurotoxicity3 Omics Driven Profiling2 Omnigenic AD architecture5 Onset vs Progression6 Oral Microbiome4 Oral-brain infection axis3 Oskar Fischer Founder27 Oxidative and nitrative stress as primary driver3 Oxidative Stress13 Oxidative stress and apoptosis pathways3 Oxidative stress as trigger3 Oxidative stress as unifying mechanism3 Oxygen as fundamental homeostatic mediator2 Oxygen deficiency as root cause5 Oxygenation-based therapeutic approach2

P 53

P. gingivalis as keystone pathogen4 PANTHOS15 Parasitic mite infestation as AD cause3 Pathogen Driven Neurodegeneration2 Pathogen-specific AD subtypes4 Pathological supersystem model3 Peptide Neurotherapeutics9 Perineuronal Nets21 Peripheral Immunocyte Regulation4 Peripheral Lipid Biomarkers3 PERK DLX1 Tau Axis5 Peroxidized ApoE as proximate cause9 Peroxynitrite-mediated neurodegeneration3 Personalized multifactorial etiology3 Phagocytic Clearance7 Pharmacological neuroprotection3 Phase Measurability6 Physics of organisms approach4 Plaque IgG Sequestration3 Plaque Origin What is Established14 Plaque-cognition dissociation4 Polymicrobial brain infection2 Polymicrobial causation of AD3 Polytherapeutic natural product approach3 Population-specific AD genetic signatures3 Post-translational modification as prion trigger3 Post-translational modification dysregulation6 Precision genomics approach3 Precision Medicine AD5 Precision medicine approach3 Precision medicine for AD3 Precision medicine protocol5 Preclinical Phase Activity5 Presymptomatic Lipidomic Signatures2 Prion infectivity distinct from insoluble protein accumulation5 Prion-like disease propagation9 Probabilistic multi-cause disease etiology3 Production-clearance equilibrium7 Programmed aging clock model of AD3 Proteasome Tau Feedback8 Protein biosynthesis interference as root cause4 Protein denaturation as disease driver3 Protein Misfolding3 Protein templating and seeding7 Proteoglycan role in amyloid formation3 Proteostasis11 Proteostasis Collapse1 Proteostasis disruption3 Psychological origins of neurodegeneration3 Psychology as primary disease trigger3 Psychosocial Risk Factors4 Psychosomatic cascade to neurodegeneration3 Psychosomatic model of Alzheimer's disease3

Q 2

Quality Control Collapse9 Quantum consciousness in neurons3

R 17

Reasoning-numerical cognitive separation4 Receptor-based therapeutic approach3 Receptor-mediated amyloid internalization5 Redox chemistry therapeutic approach3 Redox signaling as central mechanism3 Reelin-ApoE receptor axis disruption27 Region-selective neuronal vulnerability7 Repurposing antihypertensives for AD3 Resilience as key to understanding AD clinical expression3 Retrogenesis model4 Retrotransposon Activation5 Retroviral-like mechanisms drive disease propagation9 Revisiting failed drug trials3 Risk factor convergence3 RNA-based diagnostics and therapeutics5 ROS-calcium signaling axis3 Runaway synaptic modification hypothesis3

S 53

Selective Tau Disruption4 selective vulnerability of PV interneurons10 Self-DMN dysfunction hypothesis3 Sense-making failure and cellular conflict4 Sensory Loss Dementia Correlation4 Sex Differences in Tauopathy2 Sex Dimorphic AD Mechanisms3 Sex Specific MiRNA Signatures3 Sex-based hemoglobin differential3 Sex-specific AD vulnerability3 Sex-specific disease mechanisms5 Sigma-1 receptor-mediated neuroprotection3 Signal Insufficiency Model (SIM)5 Silica water as protective intervention4 Single Cell AD Signatures5 Sinus-brain barrier breach enabling neurodegeneration3 SIRT1 neuroprotection3 Sleep position and brain maintenance5 Sleep posture and brain maintenance3 Sleep timing and gravitational stretching5 Sleep-AD connection3 Small molecule polypharmacology3 Small ncRNA regulation of neurodegeneration5 Solar gravitational muscle constriction theory4 Somatic Mosaicism in AD7 Somatic mutations as novel therapeutic targets8 Somatic recombination creates pathogenic gene variants13 SORL1 Lysosomal Function6 SorLA Lipid ER Regulation6 Sphingolipid Signaling4 Spiritual and karmic etiology3 SSRI repurposing for neurodegeneration3 Staged anatomical progression7 Substance abuse and neurodegeneration3 Sundowner symptoms from evening muscle constriction4 SuperAgers demonstrate pathology-cognition dissociation4 Synapse loss as primary event3 Synaptic Competition4 Synaptic dysfunction as primary driver3 Synaptic impairment as primary pathomechanism3 Synaptic Pathology13 Synaptic Physiology2 Synaptic Plasticity12 Synaptic plasticity failure3 Synaptoblastic vs synaptoclastic balance8 Syndromic Complexity3 Systemic circulating factors governing neurodegeneration4 Systemic disease beyond CNS3 Systemic disease interaction model3 Systemic to Central Immune Signaling3 Systems approach to interconnected AD pathological hallmarks3 Systems Biology9 Systems thinking and feedback loops4

T 31

T14 feedforward toxicity cascade5 T14 Toxin Antagonism6 Tau as conditional prion6 Tau as primary causative factor over amyloid3 Tau Biomarkers6 Tau Pathology22 Tau prions drive disease more than Abeta prions5 Tau Propagation20 Tau Scaffolding Interactions5 Tauopathy primacy over amyloidopathy5 Tauopathy Sleep Disruption2 Temperature-dependent protein misfolding3 Terminal thoughts and genetic change3 Theoretical brain cognition framework4 Theory integration across domains6 Three-actor-group pathogenesis3 Threshold and set point model for neurodegeneration3 TNF-alpha as central AD mediator3 TOMM40 Import Gate19 Torsion field theory of AD3 Toxic Abeta species and PTMs3 Traditional medicine integration4 Trained Immunity6 Transcriptional Pause Release6 Transcriptomic Isoform Complexity5 Translational Regulation in Tauopathy5 Transsulfuration pathway dysfunction3 Transsynaptic tau propagation7 Trauma Induced Viral Reactivation3 TXNIP as therapeutic target3 Type 2 diabetes as AD risk factor3

U 2

Understanding Abeta function key to early identification3 Unified theory of AD etiology5

V 13

Vascular Amyloid Interaction5 Vascular and inflammatory contributions3 Vascular dysfunction as earliest detectable change3 Vascular insufficiency hypothesis3 Vascular-mechanical etiology3 Vascular-metabolic-infectious convergence3 Vascular-sleep interaction3 Vesicular Trafficking5 Vessel Associated Microglial Activation7 Viral infection triggers chronic brain inflammation7 Viral Pathogenesis3 Viral trigger hypothesis for neurodegeneration3 Vitamin E-miRNA-inflammation axis4

W 2

Wear and tear accumulation3 Wnt-GSK3-beta pathway integrating amyloid and tau pathology3

Z 1

Zeitgeber-driven neurodegeneration3