see also:

• neurology
• Mental state - delirium vs dementia vs psychosis
• cognition
• Behavioural and Psychological Symptoms of Dementia (BPSD)

• dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging.
• affected areas of cognition may be memory, attention, language, and problem solving.

• various types of brain injury, occurring as a single event resulting in long term cognitive deficit:
  • trauma
  • hypoxic events (eg. near drowning)
  • stroke (CVA)
  • prolonged seizures
  • acute hydrocephalus
  • meningitis
  • encephalitis
• substance abuse which may result in long term fixed cognitive deficits despite cessation of substance abuse:
  • alcoholic dementia
  • Wernicke's encephalopathy
  • Korsakoff's psychosis
  • other recreational substance abuse

• Alzheimer's dementia (AD)
  • usually slow progression but may have a rapid progressive onset
  • most often, it is diagnosed in people over 65 years of age, although the less-prevalent early-onset Alzheimer's can occur much earlier.
    • people with Down's syndrome are at higher risk of developing early onset AD and often have amyloid plaques by age 40
  • predicted to affect 1 in 85 people globally by 2050
• Lewy Body dementia (LBD)
  • a type of dementia closely allied to both Alzheimers and Parkinson's Diseases. It is characterized anatomically by the presence of Lewy bodies, clumps of alpha-synuclein and ubiquitin protein in neurons
  • often has a rapid or acute onset, with especially rapid decline in the first few months.
  • fluctuating cognition with great variations in attention and alertness from day to day and hour to hour
  • recurrent visual hallucinations in 75% pts
  • motor features of Parkinson's
  • often have frequent falls &/or postural hypotension/syncope
  • rapid eye movement sleep behavior disorder
  • one of the most clinically critical and distinctive features is hypersensitivity to neuroleptic and antiemetic medications that affect dopaminergic and cholinergic systems as they may become catatonic, lose cognitive function and/or develop life-threatening muscle rigidity (neuroleptic malignant syndrome (NMS))
• vascular or multi-infarct dementia
  • often small infarcts go unrecognised at the time of infarctions
  • may be due to antiphospholipid syndrome, CADASIL, MELAS, homocystinuria, moyamoya and Binswanger's disease
• frontotemporal lobar degeneration (FTLD) dementia
  • the 2nd most common cause of dementia in those under 65yrs age, and the 4th most common cause in those over 65 yrs of age (when vascular and Lewy Body dementia become more common)
  • ~40% are genetic, and most have tau or ubiquitin inclusions on histology
  • 3 clinical subtypes:
    • behavioural-variant frontotemporal dementia
      • apathy or disinhibition
      • complex planning problems
      • frontal reflexes such as palmomental reflex sign
    • semantic dementia
      • fluent aphasia, anomia, impaired comprehension of word meaning, and visual associative agnosia (inability to match semantically-related pictures or objects)
      • presumably the type affecting actor Bruce Willis
    • progressive nonfluent aphasia
      • progressive difficulties with speech production - hesitant, effortful speech, return of childhood stutter
• repetitive brain trauma
  • eg. boxers (dementia pugilistica)
• Parkinson's disease with dementia
  • dementia onset is more than 1 year after the onset of Parkinson's (if dementia begins within 12 months of onset of Parkinson's then it is most likely to be Lewy Body Dementia)
• normal pressure hydrocephalus
  • wide based gait
• syphilis
• HIV / AIDS
• Lyme disease
• vitamin deficiency - eg. B12, folate or niacin and perhaps vitamin C
• low blood pressure
  • adults with hypotension in the UK Biobank were about three times more likely to develop Alzheimer's while those with high blood pressure had 1.6x risk and those with AF had 1.5x risk¹⁾
• adolescent behaviours such as alcohol or drug use
  • adolescent alcohol intoxication gives ~5x risk of young onset dementia (YOD) in men (median age onset 54yrs), this increases to 20x risk if combined with 2 other risk factors such as depression, antipsychotic use, substance abuse, FH father with dementia, stroke, high systolic BP, or being in lower 1/3rd percentiles for cognition or height. These 9 factors accounted for 68% of all cases of young onset dementia in the 0.5 million men followed up, 1 in 1000 of whom developed YOD. ²⁾

• Huntington's disease
• fragile X carriers
  • Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder associated with problems with movement (intentional tremor, Parkinsonism), memory, dysautonomia and peripheral neuropathy. This is clinically different to Fragile X syndrome.
• familial Alzheimer's disease
• other Alzheimer's disease
  • 80% heritability
  • two new genetic variants and 95 new gene interactions (epistasis) that may modulate the effects of variants in Alzheimer’s discovered by CSIRO in 2023
  • H63D variant of HFE gene which is linked to haemochromatosis, doubles risk of dementia in men ³⁾
  • variants of the aquaporin‑4 (AQP4) gene, which helps regulate the glymphatic system of the brain which clears toxins from the brain, particularly while you sleep
    • those carrying certain AQP4 variants showed faster grey matter loss when they reported shorter sleep⁴⁾
• SCA17 (dominant inheritance)
• adrenoleukodystrophy (X-linked)
• Gaucher's disease type 3
• metachromatic leukodystrophy
• Niemann-Pick disease type C
• pantothenate kinase-associated neurodegeneration
• Tay-Sachs disease
• Wilson's disease

• BMAA toxin from blue green algae
  • high levels of the BMAA toxin produced by blue green algae has been shown to produce brain tangles and amyloid deposits in vervets and this was partly reduced by supplementing their diet with L-serine ⁵⁾
    • Chammoro villagers from the Pacific island of Guam developed a dementia syndrome from eating flour made from the seeds of cycads, the roots of which were exposed to blue green algae and the BMAA toxin
    • might be wise to avoid exposure to BMAA and avoid swimming or drinking water from rivers and lakes with this, and perhaps reduce consumption of seafoods which are exposed to it such as mussels, prawns and crabs which feed on the algae, but don't take L-serine supplements until they are proven safe
• aberrant S-nitrosylation reactions (due to PM2.5, nitrates, etc) contribute to some forms of cancer, autism, Alzheimer's disease, Parkinson's disease and other conditions
  • S-nitrosylation of protein CRTC1, impairs its ability to regulate genes that are critical for forming and maintaining connections between brain cells, an essential process for learning and long-term memory⁶⁾
• chronic gingivitis appears to have a role
• low dietary magnesium intake
  • there appears to be a protective effect of higher dietary magnesium (550mg/day compared to “normal” intake of 300mg/d) on reducing brain aging, reduction in brain size and dementia ⁷⁾
• fish oil supplementation does not seem to be a benefit for preventing AD⁸⁾
• caffeine intake does seem to reduce onset of dementia
• loneliness under age 80yrs appears to increase risk of dementia 3-fold according to a 2022 study of 2,300 participants in the population-based Framingham Study, and lonely participants without dementia had signs of cognitive problems, including poorer executive function, lower total cerebral volume and greater brain white-matter injury.

• ?disease amplifying role of Chlamydia pneumoniae long term infection in retina⁹⁾
• Behçet's disease
• multiple sclerosis
• sarcoidosis
• Sjögren's syndrome
• systemic lupus erythematosus

• Alzheimer's dementia (AD)
• Lewy Body dementia (LBD)
• frontotemporal lobar degeneration (FTLD) dementia
• Creutzfeldt-Jakob disease typically causes a dementia which worsens over weeks to months
• progressive multifocal leukoencephalopathy (PML)
• NB. encephalopathy or delirium may develop relatively slowly and resemble dementia