Neurology

• Minimally Conscious State: https://www.neurology.org/doi/10.1212/WNL.58.3.349

• Sagging Eye Syndrome: lateral rectus & superior rectus band ligament 10.1001/jamaophthalmol.2013.783 https://www.doi.org/10.1001/jamaophthalmol.2013.783

The boundaries between these variants are increasingly recognized as graded rather than categorical, with overlapping features and mixed phenotypes common. Additionally, most AD patients exhibit co-pathologies such as cerebrovascular lesions, Lewy body pathology, or TDP-43 proteinopathy, which influence clinical presentation and disease progression.

Based on neurofibrillary tangles (NFT), tau distribution. Amyloid beta is usually diffuse.

Acceleration of tau spread (stage I ~ 16 years, stage IV ~ 5 years).

Without dementia: 1–2, clinically proven AD: 3–5

Primary sources of acetylcholine for cortex, hippocampus, and amygdala.

Nucleus Basalis of Meynert subdivisions:

Neuritic plaques are senile (Aβ) plaques associated with neuronal injury. Distinguished from diffuse plaques by presence of dystrophic neurites (swollen, contain phoshorylated tau immunoreactivity). Both Aβ and tau pathology.

Density of neuritic plaques in neocortex only!!!

• A: Amyloid ᷩβ (Thal)
• B: Braak stage
• C: CERAD (Concortium to Establish a Registry for Alzheimer's disease)

  A Score (Thal Phase)	C Score (CERAD)	B0–B1	B2 (Braak III–IV)	B3 (Braak V–VI)
  A0	C0	Not	Not	Not
  A1	C0 or C1	Low	Low	Low
  A1	C2 or C3	Low	Intermediate	Intermediate
  A2	Any C	Low	Intermediate	Intermediate
  A3	C0 or C1	Low	Intermediate	Intermediate
  A3	C2 or C3	Low	Intermediate	High

"Intermediate" or "High" AD neuropathologic change is considered a sufficient neuropathologic explanation for dementia. In a validation cohort of 562 individuals, 91% of those with Braak V–VI and frequent CERAD neuritic plaques had moderate or severe dementia, while just over half of those with intermediate-level pathology (Braak III–IV, moderate CERAD) had at least mild dementia.

Key Distinctions from Thal Phases: While both assess Aβ pathology, they measure fundamentally different things:

• Thal phases assess the anatomic spread of all Aβ plaques (diffuse and dense-core) across brain regions.
• CERAD assesses the density of specifically neuritic plaques in the neocortex — the plaque subtype most closely linked to neuronal damage and clinical symptoms.

This is why both are included in the ABC system — a brain could have widespread diffuse Aβ deposits (high Thal phase) but few neuritic plaques (low CERAD), or vice versa, and these scenarios carry different clinical implications.

In the NIA-AA validation cohort (n = 562), the ABC system performs robustly in the general elderly population:

• High AD neuropathologic change (B3/C3: Braak V-VI and frequent CERAD neuritic plaques): 91 % had moderate or severe dementia.
• Intermediate AD neuropathologic change (B2/C2: Braak III-IV, moderate CERAD): just over half had at least mild dementia.

Importantly, among the individual ABC components, Braak NFT stage (B) and CERAD neuritic plaque score (C) independently predict cognitive impairment, whereas Thal amyloid phase (A) does not significantly add to cognitive prediction beyond B and C scores — suggesting that diffuse Aβ deposits captured by Thal staging are relatively neutral with respect to cognition.

Several factors distinguish cognitively resilient individuals from those who develop dementia despite equivalent ADNC:

• Lower tau burden relative to Aβ. In the Dutch 100-plus Study, 5 centenarians maintained high cognition despite AD-level Aβ loads; they had significantly less tau pathology than cognitively impaired centenarians with comparable Aβ. This supports the view that Aβ alone is insufficient — it is the downstream tau propagation that drives clinical decline.
• Cognitive reserve factors — higher education, occupational complexity, and greater premorbid IQ — are consistently associated with better-than-expected cognitive performance relative to neuropathologic burden. Greater baseline cortical thickness (brain reserve) also predicts cognitive resilience to tau pathology.
• Fewer non-Alzheimer's disease neuropathologic changes comorbidities. Among oldest-old individuals with intermediate/high ADNC, those who remained cognitively normal had significantly fewer co-occurring neurodegenerative pathologies (LATE-NC, LBD, hippocampal sclerosis). A high number of non-ADNC pathologies carried an OR of 4.46 for dementia.

These findings suggest that in the oldest-old, ADNC alone is neither necessary nor sufficient for dementia — the clinical outcome depends on the total neuropathologic burden, the specific combination of co-pathologies, and individual resilience factors. This has direct relevance for anti-amyloid therapies: targeting Aβ alone may have limited benefit in the very elderly, where non-ADNC pathologies contribute substantially to cognitive decline and where a significant proportion of individuals tolerate high ADNC without clinical consequences.

https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18124

• Priming
• Procedurální paměť
• Asociativní učení a operantní podmiňování
• Neasociativní učení: habituace a sensitizace

• Semantická
• Epizodická

Neurobiologická podstata:

• Kódování
• Uložení
• Konsolidace
• Vybavení
• Prefrontální kortex (H.M.)
• Konstruktivní proces

• Okruhy vs. centra
• Vzdálený efekt (subkortikální afázie atd.)
• doi 10.1177/1073858413494269

  Default mode network	mediální frontální kůra, zadní cingulum, precuneus, gyrus angularis
  Dorsal attention network	intraparietální sulcus, frontal eye field
  Ventral attention network (salience)	přední insula, přední cingulum
  Fronto-parietal control network (central executive)	dorsolaterální prefrontální kortex, intraparietální sulcus

Sporadic disease (sCJD):

Heidenhain variant (HvCJD): occipital cortex, most commonly MM1, can also occur with MM2C, and rarely MV1.

Doi 10.1111/cen.70049:

1. Confirm hyponatremia (serum Na+ < 135 mEq/l and serum osmolarity < 275 mOsm/kg).
2. Assess ECF Volume Status (Clinically or via CVP, BUN/Cr, Hct): Hypovolemia? Euvolemia?
3. Measure urine and blood uric acid and creatinine and calculate fractional excretion of uric acid (FEurate).
4. Correct hyponatremia (saline infusion or fluid restriction). Recheck FEurate.
5. FEurate remains > 10 % => confirms cerebral salt wasting or renal salt wasting => Increased FEPO4 as supportive marker, BNP variable.
6. FEurate normalizes => confirms SIADH => normal FEPO4 as supportive marker, BNP variable.