Memory Impairments: Type, Causes, and Molecular Players-Memory Dysfunction Across Neurologic Insults.

ingentiumby ingentium

In Discovery Literature.

Publication date: May 18, 2026

Viral infections of the central nervous system produce memory impairment through mechanisms that extend beyond acute neuronal injury. Herpes simplex virus type 1, human immunodeficiency virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, influenza, SARS-CoV-2, West Nile virus, and Zika virus each enter or engage the brain through distinct routes, yet converge on four shared molecular pathways that selectively damage hippocampal circuits: mitochondria-associated membrane (MAM) dysfunction, chronic neuroinflammation, blood-brain barrier (BBB) disruption, and impaired CREB-BDNF signaling. These pathways specifically compromise the dentate gyrus, CA3, and CA1 subfields, producing predictable deficits in pattern separation, associative retrieval, and temporal memory binding. Antiretroviral and antiviral therapies suppress viral replication but fail to reverse organelle-level dysfunction, leaving most hippocampal injury unaddressed. Emerging plasma biomarkers, p-tau217, neurofilament light chain, and GFAP, combined with hippocampal subfield MRI, now enable mechanistic stratification before irreversible circuit loss occurs. This review proposes, as a unifying hypothesis, that virus-associated memory impairment represents a convergent hippocampal syndrome driven by shared downstream pathways, and that combination therapies targeting these pathways simultaneously offer greater therapeutic promise than pathogen-specific approaches alone. The evidentiary basis for this framework varies across pathogens and conditions; direct mechanistic evidence, mechanistic analogy, and preclinical data are distinguished throughout.

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Concepts Keywords
Cytomegalovirus Animals
Influenza Hippocampus
Mri Humans
Organelle Memory Disorders
Predictable memory impairment
neurodegenerative diseases
other stimuli
viruses

Semantics

Type Source Name
disease MESH Viral infections
disease MESH injury
disease MESH Herpes simplex
disease MESH varicella
disease MESH zoster
disease MESH influenza
disease MESH neuroinflammation
pathway KEGG Viral replication
disease MESH syndrome
disease MESH dys
disease MESH neurodegenerative diseases
pathway REACTOME Neurodegenerative Diseases
disease MESH dis
disease MESH amyloid plaques
disease MESH stroke
disease MESH ischemia
disease MESH post traumatic stress disorder
disease MESH dissociation
disease MESH tic
pathway REACTOME Metabolism
disease MESH included
drug DRUGBANK Hyaluronic acid
drug DRUGBANK Thiamine
disease MESH dementia
disease MESH death
pathway KEGG Tight junction
disease MESH Vascular Dementia
disease MESH infarct
drug DRUGBANK Sulodexide
disease MESH demyelination
disease MESH Lewy Body Dementia
disease MESH LBD
disease MESH PDD
disease MESH memory deficits
disease MESH visual hallucinations
disease MESH REM sleep behavior disorder
disease MESH mitochondrial dysfunction
disease MESH PARK2
drug DRUGBANK Dopamine
disease MESH Progressive Supranuclear Palsy
disease MESH Multiple System Atrophy
disease MESH Normal Pressure Hydrocephalus
disease MESH Corticobasal Syndrome
disease MESH PSP
drug DRUGBANK Coenzyme M
disease MESH cognitive impairment
drug DRUGBANK Methylergometrine
drug DRUGBANK Cannabidiol
disease MESH CBD
disease MESH FTLD
disease MESH Spinocerebellar Ataxias
disease MESH Friedreich’s Ataxia
disease MESH FRDA
drug DRUGBANK Iron
drug DRUGBANK Omaveloxolone
disease MESH Frontotemporal Dementia
disease MESH primary progressive aphasia
drug DRUGBANK Thiocolchicoside
disease MESH atrophy
disease MESH CJD
disease MESH prion diseases
disease MESH sporadic CJD
drug DRUGBANK Trestolone
disease MESH Korsakoff Syndrome
disease MESH thiamine deficiency
drug DRUGBANK Ethanol
disease MESH retrograde amnesia
disease MESH Chronic Traumatic Encephalopathy
disease MESH CTE
disease MESH head trauma
disease MESH encephalitis
drug DRUGBANK Phenylpropanolamine
disease MESH PPA
drug DRUGBANK Isoxaflutole
disease MESH cerebrovascular disorders
disease MESH Alzheimer’s Disease
disease MESH Parkinson’s Disease
disease MESH Lateral Sclerosis
disease MESH Huntington’s Disease
disease MESH Amyotrophic Lateral Sclerosis
pathway KEGG Amyotrophic lateral sclerosis
disease MESH vascular injury
drug DRUGBANK Angiotensin II
disease MESH multiple sclerosis
disease MESH NOD
disease MESH severe acute respiratory syndrome
disease MESH premature aging
disease MESH arteritis
disease MESH thrombosis
disease MESH hemorrhagic stroke
disease MESH inflammation
drug DRUGBANK Methionine
disease MESH cytokine storm
disease MESH brain fog
disease MESH long COVID
disease MESH infection
disease MESH microcephaly
disease MESH necrosis
pathway REACTOME CREB phosphorylation
disease MESH neurocognitive disorder
drug DRUGBANK Calcium
disease MESH HIV infection
pathway REACTOME HIV Infection
pathway REACTOME Complement cascade
pathway REACTOME Mitophagy
disease MESH SARS CoV 2 infection
drug DRUGBANK ATP
disease MESH astrogliosis
disease MESH NS5
pathway REACTOME Apoptosis
disease MESH ZIKV infection
disease MESH traumatic brain injury
disease MESH Cerebral Palsy
disease MESH Hypoxia
drug DRUGBANK Methyl isocyanate
pathway KEGG Oxidative phosphorylation
pathway REACTOME Fatty acids
drug DRUGBANK Arachidonic Acid
drug DRUGBANK Doconexent
drug DRUGBANK Histamine
drug DRUGBANK Cyclic Adenosine Monophosphate
pathway REACTOME Mitochondrial biogenesis
disease MESH encephalopathy
drug DRUGBANK Nadide
drug DRUGBANK Nicotinamide Mononucleotide
drug DRUGBANK Nicotinamide
drug DRUGBANK PDE4
disease MESH TAR
drug DRUGBANK Cholesterol
drug DRUGBANK 3 7 11 15-Tetramethyl-Hexadecan-1-Ol
disease MESH Arc
drug DRUGBANK Rolipram
drug DRUGBANK Metformin
drug DRUGBANK Ketamine
drug DRUGBANK Serine
drug DRUGBANK L-Threonine
drug DRUGBANK Tideglusib
pathway REACTOME DAP12 signaling
drug DRUGBANK Resveratrol
pathway REACTOME Translation
disease MESH pact
drug DRUGBANK Estradiol
drug DRUGBANK Human Serum Albumin
disease MESH Psychiatric Disorders
disease MESH Major Depressive Disorder
disease MESH cognitive symptoms
disease MESH Schizophrenia
disease MESH psychosis
drug DRUGBANK Minocycline
drug DRUGBANK Acetylcysteine
disease MESH PTSD
disease MESH Bipolar Disorder
disease MESH Brain injury
disease MESH diffuse axonal injury
pathway KEGG Ferroptosis
disease MESH sleep disordered breathing
disease MESH Brain Tumors
disease MESH edema
disease MESH seizure
disease MESH tumor
disease MESH AChE
disease MESH PDE
drug DRUGBANK Donepezil
drug DRUGBANK Rivastigmine
drug DRUGBANK Galantamine
drug DRUGBANK Masitinib
drug DRUGBANK Memantine
drug DRUGBANK Azeliragon
drug DRUGBANK Levodopa
drug DRUGBANK Nilotinib
pathway REACTOME Autophagy
drug DRUGBANK Lauric Acid
disease MESH Abl
drug DRUGBANK Exenatide
drug DRUGBANK Neflamapimod
drug DRUGBANK Tetrabenazine
drug DRUGBANK Deutetrabenazine
drug DRUGBANK Pridopidine
drug DRUGBANK Cilostazol
disease MESH mixed dementia
drug DRUGBANK Davunetide
drug DRUGBANK Rasagiline
drug DRUGBANK Riluzole
drug DRUGBANK Rifampicin
drug DRUGBANK Edaravone
drug DRUGBANK Verdiperstat
drug DRUGBANK Quinacrine
drug DRUGBANK Pentosan Polysulfate
drug DRUGBANK Dasatinib
drug DRUGBANK Tropicamide
disease MESH sarcoma
disease MESH hypertension
drug DRUGBANK L-Leucine
drug DRUGBANK Trihexyphenidyl
drug DRUGBANK Profenamine
disease MESH PTEN
drug DRUGBANK Hydrogen peroxide
disease MESH Chai
pathway KEGG Alzheimer disease
disease MESH alpha synucleinopathies
disease MESH Park
disease MESH Cerebral Infarction
drug DRUGBANK Uric Acid
disease MESH Burn
pathway KEGG Parkinson disease
pathway KEGG Huntington disease
disease MESH Vasculitis
disease MESH Cytomegalovirus infection
disease MESH West Nile virus infection
disease MESH mood disorders
disease MESH Metabolic Diseases
disease MESH Mania
drug DRUGBANK Carboxyamidotriazole
disease MESH Glioblastoma

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