Differentials
Common
Mild cognitive impairment (MCI)
History
activities of daily living intact, functional activities preserved with minimal impairment particularly on complex instrumental activities of daily living[84]
Exam
Folstein MMSE score <24
1st investigation
- Folstein MMSE:
<24
Delirium
History
Exam
1st investigation
- FBC:
may be WBC >9 x 10⁹/L (>11 x 10³/microlitre) or <3 x 10⁹/L (<3 x 10³/microlitre
More - metabolic panel:
may be Na >145 mmol/L (145 mEq/L) or <135 mmol/L (135 mEq/L); K >5.5 mmol/L (5.5 mEq/L) or <3.5 mmol/L (3.5 mEq/L); HCO₃ >30 mmol/L (30 mEq/L) or <22 mmol/L (22 mEq/L); Cr >106 micromol/L (1.2 mg/dL); glucose <3.9 mmol/L (70 mg/dL), (after fasting)
More - chest x-ray:
in presence of pneumonia: consolidation demonstrated
More - urinalysis:
may be positive leukocyte esterase, nitrites
More
Other investigations
- urine culture:
may be bacterial or fungal growth
More - 4AT tool:
consists of 4 items (alertness; AMT4 [Abbreviated Mental Test - 4]; attention; acute change); scored from 0-12, ≥4 indicates possible delirium, 1-3 indicates possible cognitive impairment 4AT rapid clinical test for delirium Opens in new window
More
Depression
History
persistent dysphoric mood, anhedonia (loss of interest in usual activities), impaired recall with relative sparing of recognition memory, poor concentration, sleep and appetite disturbances, energy loss, psychomotor retardation, feelings of worthlessness and guilt, recurrent thoughts of death[65]
Exam
suicidal ideation, problems with attention, concentration, and recent memory
1st investigation
- Folstein MMSE:
problems with attention, concentration, recent memory
Other investigations
Alzheimer's dementia
Vascular dementia
History
Exam
may have hemiparesis, asymmetric deep tendon reflexes, unilateral extensor plantar response, visual field deficits, gait abnormalities, hypertension, dysrhythmias (e.g., atrial fibrillation), carotid bruits, congestive heart failure, diabetes, emotional incontinence (excessive mood lability); cognitive decline on screening test[68]
1st investigation
- CT/MRI head:
ischaemic infarction, hippocampal volume loss
More
Other investigations
Lewy body dementia
History
history of fluctuating cognitive performance, episodes of incoherent speech, variable attention (e.g., well-formed visual hallucinations unrelated to dopaminergic therapy), history of parkinsonism emerging simultaneously with cognitive impairment[85]
Exam
muscle rigidity, stooped posture, cog-wheeling, well-formed visual hallucinations, and cognitive fluctuations
1st investigation
- CT/MRI head:
hippocampal volume loss
More
Uncommon
Amnestic syndromes
Aphasia
History
acute onset (hours/days), history of transient ischaemic attack or stroke
Exam
inability to comprehend instructions, repeat words or phrases, or to read, sparse verbal output (lesion of dominant hemisphere), fluent verbal output with word substitutions/paraphasias and impaired comprehension (lesion in Wernicke's area), anomia (Alzheimer's disease or frontal lobe degenerative dementia)[89][90]
1st investigation
- CT head:
focal or diffuse areas of ischaemia
Other investigations
Frontotemporal dementia
History
disinhibition, impulsiveness, social inappropriateness, apathy, withdrawal
Exam
disinhibition, lack of executive function, passivity[98]
1st investigation
- none:
disease can often be recognised clinically before changes on routine imaging are apparent
Other investigations
- CT/MRI head:
visualisation of focal atrophy in frontal and temporal lobes
Parkinson's disease
History
shaking, stiffness, slowness or poverty of movement, anxiety, apathy, falls, hypersomnolence, bowel and bladder dysfunction[99]
Exam
tremor at rest, rigidity on passive movement, bradykinesia (slowness of movement), poverty of movement (hypokinesia), orthostatic hypotension, and postural instability[99]
1st investigation
- none:
diagnosis made based on clinical exam findings of resting tremor, bradykinesia, hypokinesia, rigidity
Other investigations
Huntington's disease
History
progressive involuntary movements, neuropsychiatric disturbances, cognitive impairments (e.g., executive function, immediate memory)[100]
Exam
involuntary movements, executive function deficits, deficits in visuospatial abilities, short-term and long-term memory deficits[100]
1st investigation
- serum genetic testing:
abnormal trinucleotide CAG repeat sequence
Other investigations
Brain tumours
Cushing's syndrome
History
sudden onset of central weight gain, oligomenorrhoea or amenorrhoea, spontaneous ecchymoses, florid complexion, difficulty climbing stairs or rising from a low chair, depression[102]
Exam
thickening of facial fat (moon faces), facial telangiectasias, enlarged dorsocervical fat pad (buffalo hump), hypertension, violaceous striae on the abdomen or proximal extremities, acne, mild hirsutism, central fat deposition[102]
1st investigation
Other investigations
Hypopituitarism
History
energy loss, muscle weakness, decreased sweating, anorexia, weight loss or weight gain, abdominal pain, reduction in amount of axillary and pubic hair in women, erectile dysfunction, oligomenorrhoea/amenorrhoea, breast atrophy, loss of libido, infertility, cold intolerance, dry skin, polyuria, polydipsia, nocturia[103]
Exam
may have increased central adiposity, dry skin, reduced muscle mass and strength, visual field defects, circulatory collapse if acute presentation[103]
1st investigation
- LH:
low
- FSH:
low
- oestrogen:
low
More - TSH:
low
- free T4 and T3:
low
- basal serum cortisol:
low
Other investigations
- testosterone:
low
- prolactin:
low
- cortisol and growth hormone reserve:
low
- FBC:
anaemia
- metabolic panel:
hyponatraemia, hyperkalaemia, hypoglycaemia
- insulin tolerance test:
reduced growth hormone response
More - urine specific gravity:
low in diabetes insipidus
- water deprivation test:
urine is more dilute after administration of desmopressin
More
Primary hyperparathyroidism
Acute intermittent porphyria
History
severe abdominal pain, muscular weakness, constipation, nausea, vomiting, psychiatric disturbances, dark urine, chest pain, back pain, exposure to barbiturates, oestrogens, sulphonamides, phenytoin, chloramphenicol, tetracyclines, antihistamines, emotional or physical stress, premenstrual, alcohol, smoking[105]
Exam
sensory neuropathy, peripheral motor neuropathy, absent reflexes, hypertension, coma[105]
Other investigations
Primary hypothyroidism
History
fatigue, cold intolerance, dry skin, hoarse voice, constipation, weight gain, depression, muscle weakness
Exam
dry skin, muscle weakness, bradycardia
1st investigation
- TSH:
high
- free T4:
low
- free T3:
low
Other investigations
Hyperthyroidism
History
weight loss, heat intolerance, restlessness, anxiety, diarrhoea, bulging eyes, hand tremor
Exam
exophthalmos, clammy skin, tachycardia, goitre, high blood pressure
1st investigation
- TSH:
low
- free T4:
high
- free T3:
high
Other investigations
Wilson's disease
History
family history of liver and neurological disease;[106] neurological and psychiatric presentation includes: tremor, involuntary movements, dystonia, bizarre behaviour, emotional lability, depression, personality changes, psychosis, dysarthria, drooling, seizures, migraine headaches, pseudobulbar palsy[107]
Exam
Kaiser-Fleischer rings, tremor, dystonia, rigidity, dysarthria, drooling[107]
Other investigations
- liver biopsy:
excessive copper deposition
Vitamin B12 deficiency
History
paraesthesias, memory loss, gait disturbances; presence of risk factors: age >65 years, history of gastrectomy or gastric bypass, vegan or strict vegetarian diet, chronic gastrointestinal illness, use of proton-pump inhibitors, H2 receptor antagonists, metformin, anticonvulsants
Exam
ataxia, peripheral neuropathy, decreased vibration sense, positive Romberg test, atrophic glossitis, angular cheilitis
1st investigation
- cobalamin level:
decreased
Other investigations
- red cell volume:
elevated
- homocysteine:
elevated
- methylmalonic acid:
elevated
Traumatic brain injury
History
history of head injury, headache, lethargy, loss of consciousness after head injury (subdural haematoma)
Exam
altered level of consciousness, slurred speech, hemiparesis (subdural haematoma)
1st investigation
- CT head:
subdural haematoma
Other investigations
Lyme disease
Tuberculosis
History
history of tuberculosis (TB) contact, cough, weight loss, and night sweats in addition to symptoms of meningitis
Exam
may be concomitant signs of TB pneumonia, pleural effusion, in addition to signs of meningitis
1st investigation
- chest x-ray:
consolidation, pulmonary infiltrates, mediastinal or hilar lymphadenopathy, upper zone fibrosis
More - sputum acid-fast bacilli smear and culture:
presence of acid-fast bacilli (Ziehl-Neelsen stain) in specimen
More - acid-fast bacilli smear and culture of extrapulmonary biopsy specimen:
positive
More - nucleic acid amplification tests (NAAT):
positive for M tuberculosis
More
]
Syphilis (late)
History
maculopapular rash, ataxia, personality changes, headaches, impaired memory[108]
Exam
1st investigation
- enzyme immunosorbent assay for anti-treponemal IgG/IgM:
positive
Other investigations
- Treponema pallidum particle agglutination assay (TPPA):
positive
- Treponema pallidum haemagglutination assay (TPHA):
positive
Systemic lupus erythematosus
Exam
1st investigation
- antinuclear antibodies:
positive
Other investigations
- anti-dsDNA antibodies:
positive
- anti-Sm and anti-RNP antibodies:
positive
- skin biopsy:
non-caseating granulomas
More
Sjogren's syndrome
Exam
1st investigation
- Schirmer's test:
reduced tear production
Other investigations
- slit lamp examination:
punctate keratopathy confirms keratoconjunctivitis sicca which indicates a long-standing dry eye
- anti-Ro/SSA and/or anti-La/SSB antibodies:
positive
- skin biopsy:
non-caseating granulomas
More
Sarcoidosis
Medication use
History
antihistamine use, anticholinergic use (e.g., irritable bowel syndrome); some evidence that androgen deprivation therapy may be associated with an increased risk of dementia, but this remains controversial and further investigation is required.[28]
Exam
may have chronic urticaria (requiring antihistamines)
1st investigation
- anticholinergic levels:
therapeutic range/high
- antihistamine levels:
therapeutic range/high
Other investigations
Toxin-induced
History
ingestion of alcohol, exposure to heavy metals (e.g., arsenic, lead, mercury, carbon monoxide, and cyanide)
Exam
tremor, hepatomegaly, gynaecomastia (in alcohol misuse), abdominal pain, mood disorder (in lead poisoning)
1st investigation
- urine heavy metal screen:
elevated levels of heavy metal
- gamma-glutamyltransferase (GGT):
elevated in alcohol misuse
Other investigations
Normal pressure hydrocephalus
History
headache, balance disturbances, urinary incontinence
Exam
unstable gait, slow movement, wide-based stance
1st investigation
- CT head:
hydrocephalus
- lumbar puncture:
normal, opening pressure 70 to 250 mm H₂O
More
Other investigations
Creutzfeldt-Jakob disease
History
rapidly progressive dementia, characterised by memory loss, personality changes, and hallucinations
Exam
visual impairment, speech impairment, development of akinetic mutism, myoclonus, ataxia, and seizures
1st investigation
- EEG:
characteristic triphasic spikes
Other investigations
- CSF analysis (lumbar puncture):
14-3-3 protein detected
- MRI brain:
high signal intensity in the caudate nucleus and putamen bilaterally on T2-weighted images
- MRI brain using diffusion-weighted imaging:
cortical and subcortical hyperintensities
More - brain biopsy:
dead neurons and abnormal prion proteins; brain tissues have many holes giving the brain a spongy appearance
More
Use of this content is subject to our disclaimer