Pathophysiology

Pathophysiology

P-II-32. Cognitive tests & neurodegenerative disorders (MCI)

認知機能検査と神経変性疾患（軽度認知障害）

Neurodegenerative Disorders

  • General term: acquired deterioration of cognitive functions with a degenerative or vascular cause
  • Categories:
    • Delirium (acute)
    • Major neurocognitive disorder (dementia)
    • Minor neurocognitive disorder = mild cognitive impairment (MCI)

Mild Cognitive Impairment (MCI)

  • Decline of ≥1 cognitive function vs earlier status
  • The state between normal age-related decline and dementia
  • Mild deterioration noticed by person/relatives (dates, birthdays, days)
  • Does NOT interfere with daily self-sufficiency (paying bills, medications) — but requires greater concentration
  • Not explained by delirium or other mental impairment
  • Diagnosis: tests (Addenbrooke, MMSE), lab tests, brain MRI/CT, functional brain imaging
  • No medication → cognitive training

Major Cognitive Impairment (Dementia)

  • Significant decline proven by standardized neuropsychological tests
  • Interferes with daily self-sufficiency → person needs help
  • Types:
    • Alzheimer’s: most common (age 65–74); hippocampus; (1) intracellular neurofibrillary tangles (hyperphosphorylated tau) + (2) amyloidosis (amyloid-β from APP); risk: age, sex, diabetes, smoking, high BP, inactivity; prevention: Mediterranean diet, exercise
    • Vascular dementia: usually stroke from atherosclerosis (ischemic/hemorrhagic); amyloid-β in vessel walls; multi-infarct (cortical/subcortical), strategic infarct, subcortical vascular encephalopathy
    • Lewy body dementia: α-synuclein⁺ Lewy bodies + Lewy neurites (± amyloid plaques/NFT); cortical + subcortical; parkinsonism
    • Frontotemporal dementia: proteinopathy of frontotemporal lobe; memory relatively intact, but planning/judgement/problem-solving decline; 40% familial; behavioral or language variants

Cognitive Tests

  • General status — Addenbrooke’s (ACE): scored by region — orientation (10), attention + cognitive flexibility (8), episodic & semantic memory (35), verbal fluency (14), aphasia tasks (28)
  • Memory: Rey-Osterrieth complex figure (copy + recall); Corsi (working memory, 9-square sequence); Rey auditory-verbal learning test
  • Executive: Trail Making Test A/B (flexibility, inhibition); Tower of Hanoi (planning); Wisconsin Card Sorting (set-shifting, frontal dysfunction)
  • Social cognition: recognition of emotional reactions from portraits

一問一答

▶What is mild cognitive impairment (MCI)?

A decline of one or more cognitive functions versus earlier status, representing the state between normal age-related decline and dementia.

▶What key feature distinguishes MCI from dementia?

MCI does NOT interfere with daily self-sufficiency (though it requires greater concentration), whereas dementia does.

▶How are neurodegenerative cognitive disorders categorized?

Delirium (acute), major neurocognitive disorder (dementia), and minor neurocognitive disorder (MCI).

▶What is the management of MCI?

No medication; cognitive training is used.

▶How is MCI diagnosed?

Cognitive tests (Addenbrooke, MMSE), lab tests, brain MRI/CT, and functional brain imaging, excluding delirium or other mental impairment.

▶What are the two characteristic pathological hallmarks of Alzheimer's disease?

Intracellular neurofibrillary tangles (hyperphosphorylated tau) and amyloidosis (amyloid-β derived from APP).

▶Which brain region is characteristically affected early in Alzheimer's disease?

The hippocampus.

▶What are risk factors for and preventive measures against Alzheimer's disease?

Risks: age, sex, diabetes, smoking, high BP, inactivity. Prevention: Mediterranean diet and exercise.

▶What causes vascular dementia?

Usually stroke from atherosclerosis (ischemic or hemorrhagic), with amyloid-β in vessel walls; types include multi-infarct, strategic infarct, and subcortical vascular encephalopathy.

▶What is the pathological hallmark of Lewy body dementia?

α-synuclein-positive Lewy bodies and Lewy neurites (± amyloid plaques/tangles), with parkinsonism.

▶What characterizes frontotemporal dementia?

Proteinopathy of the frontotemporal lobe with relatively intact memory but declining planning/judgement/problem-solving; ~40% familial; behavioral or language variants.

▶What is delirium in the context of cognitive disorders?

An acute (sudden-onset) form of cognitive impairment.

▶What does the Trail Making Test A/B assess?

Cognitive flexibility and inhibition (executive function).

▶What does the Wisconsin Card Sorting Test evaluate?

Set-shifting and frontal lobe dysfunction (executive function).

▶What does the Corsi block test measure?

Working memory (a 9-square spatial sequence task).

▶What does the Tower of Hanoi test assess?

Planning ability (an executive function).

▶What does the Addenbrooke's Cognitive Examination (ACE) assess?

General cognitive status by region: orientation, attention/cognitive flexibility, episodic & semantic memory, verbal fluency, and aphasia (language) tasks.

▶Which dementia is the most common, and at what age does it typically present?

Alzheimer's disease, typically at ages 65–74.

▶How is major neurocognitive disorder (dementia) confirmed?

By significant decline proven on standardized neuropsychological tests, with interference in daily self-sufficiency.

▶What protein abnormality underlies the neurofibrillary tangles of Alzheimer's disease?

Hyperphosphorylated tau protein accumulating intracellularly.