Pathomorphological markers
The diagnosis of Alzheimer's disease relies on strict morphological criteria that allow the condition to be distinguished from other atrophies. The main structural changes are the appearance of twisted neurofibrils and a sharp increase in the number of amyloid plaques in the brain tissue.
It is this pattern that allows the Alzheimer's process to be differentiated from Pick's disease. In Pick's pathology, amyloid plaques and twisted fibrils are absent. Instead, swollen pyramidal cells with special argyrophilic inclusions—Pick bodies—as well as local symmetrical atrophy of the upper cortical regions and glial proliferation are detected.
Differential diagnosis with dementia with Lewy bodies
In vivo diagnosis is often difficult because some diseases (e.g., dementia with Lewy bodies) combine features of both Alzheimer's and Parkinson's diseases. However, there are several important clinical differences:
- Mnesic disorders: in Alzheimer's disease, memory decline is significantly more pronounced and serves as the leading symptom.
- Frontal symptoms: attention deficits, reduced insight, and behavioral disorders in the Alzheimer's process are present to a lesser extent than in dementia with Lewy bodies.
- State dynamics: sharp fluctuations are atypical for most classical atrophies (including Alzheimer's disease). If a patient experiences periodic worsenings followed by a temporary recovery of cognitive function, this argues against a classical Alzheimer's course.
Differences from cerebrovascular diseases
It is critically important to distinguish primary atrophic processes from vascular dementias (e.g., in cerebral atherosclerosis). Unlike Alzheimer's disease, vascular lesions are characterized by:
- Asymmetry and focality: vascular disorders are distinguished by pronounced neurological focal signs (spastic paresis, aphasia, acalculia, agraphia).
- "Flickering" of symptoms: pathological manifestations are unstable and depend on changes in vascular tone and blood rheological properties.
- Meteorsensitivity: the patient's condition strongly depends on weather conditions and the geomagnetic situation.
- Insight into the disease: in vascular pathology, patients retain insight into their memory deficit for a long time, experience depression because of it, and attempt to compensate for amnesia by keeping detailed notes.
Association with extrapyramidal and other pathologies
Researchers hypothesize a genetic relationship between certain variants of Alzheimer's disease and Parkinson's disease. However, the latter has a different pathogenesis (degeneration of the substantia nigra — substantia nigra), manifests primarily with tremor, muscle rigidity, and hypokinesia, while dementia in Parkinson's occurs in only a small fraction (about 11%) of patients.
Huntington's chorea is also part of the differential series. Unlike late-onset Alzheimer's disease, it manifests on average at 43–44 years of age, is inherited in an autosomal dominant manner, and most often debuts with hyperkinesia, while dementia progresses gradually and automated actions remain preserved for a long time.
Features of the cognitive and behavioral profile (for comparison)
When assessing a patient's status, physicians pay attention to the specifics of cognitive deficit. If total amnesia comes to the forefront, this is an argument in favor of Alzheimer's disease. Other patterns point to alternative conditions:
- Behavioral stereotypies: if a patient constantly moves the bed away (fearful that the wall will fall) or stereotypically repeats a single phrase while crying, while maintaining clear speech and praxis, this is more characteristic of frontal atrophies (likely Pick's disease).
- Hallucinatory syndrome: the appearance of true visual hallucinations (e.g., micropsia in the form of "little people") against the background of insomnia more often indicates the onset of delirium or a vascular genesis.
Briefly: answers to topical questions
What are the main clinical manifestations and localization of pathogenesis in Parkinson's disease?
The main clinical manifestations of Parkinson's disease are extrapyramidal disorders, forming a characteristic triad, to which a fourth sign is later added. The pathogenesis of the disease is associated with the degeneration of melanin-containing neurons.
- Hypokinesia — slowness of movement.
- Rigidity — increase in muscle tone.
- Resting tremor — trembling of the limbs in a relaxed state.
- Postural instability — typically joins at a later stage.
The localization of the pathological process primarily affects the pars compacta of the substantia nigra (substantia nigra pars compacta), leading to a decrease in dopamine production in the nigrostriatal synapses.
What microscopic changes and cellular types are affected in Pick's disease?
In Pick's disease, microscopic changes are characterized by specific damage to neurons and glial tissue. Unlike Alzheimer's disease, twisted neurofibrils and a sharp increase in amyloid plaques are absent.
- Pyramidal cells — swell and contain argyrophilic spherical inclusions (Pick bodies).
- Glia — proliferation is observed.
- White matter of the brain — is frequently damaged, causing the boundary between white and gray matter to become blurred.
What neurotransmitter disorders (including cholinesterase deficiency) underlie the pathogenesis of Alzheimer's disease?
The pathogenesis of Alzheimer's disease is based on a deficiency of the neurotransmitter acetylcholine, rather than cholinesterase. The development of the disease is caused by the following disorders:
- Neuronal atrophy — cells of the cortex and subcortical structures are affected, including cholinergic neurons.
- Acetylcholine deficiency — a decrease in the concentration of this neurotransmitter occurs in the brain tissues.
To compensate for the acetylcholine deficit in pharmacotherapy, anticholinesterase agents (cholinesterase inhibitors) are used, which prevent its destruction.
Which medications (acetylcholinesterase inhibitors and memantine) are used for the pharmacotherapy of Alzheimer's disease?
For the pharmacotherapy of Alzheimer's disease, medications that compensate for acetylcholine deficiency and eliminate excitotoxicity are used.
- Selective cholinesterase inhibitors — the drugs of choice are ipidacrine, galantamine, rivastigmine, and donepezil.
- Non-selective cholinesterase inhibitors — pilocarpine and neostigmine methylsulfate (have pronounced peripheral side effects).
- Glutamate receptor blockers — memantine (exerts a nootropic effect by reducing toxicity from hyperactivation of glutamate receptors).
Acetylcholine precursors, such as choline alfoscerate, may also be used.
The difference between atrophy and atherosclerosis: "Atrophy (Alzheimer's) is symmetry and memory, whereas Atherosclerosis (Vascular) is asymmetry, focal lesions, and flickering."
Class and exam questions
What is the main pathomorphological difference between Alzheimer's disease and Pick's disease?
In Alzheimer's disease, twisted neurofibrils and amyloid plaques are detected in the brain. In Pick's disease, they are absent, but argyrophilic Pick bodies and local symmetrical cortical atrophy are present.
Can Alzheimer's disease be confused with dementia with Lewy bodies?
Yes, in vivo diagnosis is difficult. However, in dementia with Lewy bodies, mnesic disorders are less pronounced, whereas attention deficits, frontal symptoms, and severe fluctuations in condition predominate.
How to differentiate Alzheimer's dementia from vascular dementia based on neurological status?
Unlike atrophic processes, vascular disorders produce marked asymmetry and focality of symptoms (e.g., paresis, aphasia), and also depend on blood pressure and weather conditions.
What else to study on this topic
- Morphology of argyrophilic Pick bodies and their effect on pyramidal cells.
- Pathogenesis of the "flickering" of symptoms in cerebrovascular diseases.
- The role of the substantia nigra in the development of concomitant parkinsonism.
- Genetics of Huntington's chorea (pathology of chromosome 4) and the early development of cognitive deficit.
- Acute transient psychoses against the background of hemodynamic fluctuations.
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