Neuroscience 210

Global deterioration of the intellectual function in the face of unimpaired consciousness

heterogeneous, more than memory involved, organized thinking, abstract thinking, insight, judgement

• - General medical history
• - General neurological history
• - Neurobehavioural history
• - Psychiatric history
• - Toxic, nutritional and drug history
• - Family history
• - Objective examination
• - physical
• - neurological
• -neuropsychological

• Bedside Tests: MMSE and MOCA
• - Level of consciousness, ie. alert, drowsy, stuporous, etc.
• - Orientation: time, place, person • Memory: remote, recent, immediate (3 object recall)
• - Attention and concentration (serial 7’s, digit span)
• - Knowledge, insight
• - Language: - fluency, comprehension, repetition, object naming, tests for apraxia, reading, writing

frontal release signs, indicative of disfunction in frontal lobe, symptoms reflect which parts of cortex involved

• 1. pout reflex--when lips are struck with a hammer a pout is observed
• 2. glabellar reflex--person can't inhibit blinking in response to stimulation (tapping between eyes)
• 3. grasp reflex--hand closes when palm stroked
• 4. palmo mental reflex--scratch on palm induces sudden contraction of chin

• Anterior--frontal or premotor
• - behavioural changes/loss of inhibition, antisocial behaviour, irresponsible
• - frontotemporal dementias, Huntingtons

• Posterior--parietal and temporal lobe
• - disturbance of cognitive function (memory and language) without changes in behaviour
• - AD

• AD--longest course, many years to go from acute to subacute to chronic condition
• Normal pressure hydrocephalus--months to years
• CJD--months,
• encephalitis--weeks

• 1. Degenerative--degeneration of nerve cells, leads to cognitive disfunction
• - e.g. AZ, lewy body, Tauopathies (frontotemporal), HD, PD, Wilsons (abnormal amounts of copper)
• 2. Cerebrovascular
• - vascular dementia, multi-infarct, CNS vasulitis
• 3. Structural
• - normal pressure hydrocephalus, brain tumor, head injury, subdural hematoma
• 4. Infections
• - CJD, neurosyphilis, HIV, Herpes simplex encephalitis
• 5. Toxic/metabolic
• - drug induced, alcoholism, toxins, heavy metals, deficiences, hypothyroidism
• 6. immune disorders and cancer
• - lupus
• 7. Depression

• irreversible, progressive brain disease that slowly destroys memory and thinking skills
• - originally thought to be for middle, younger people ,discovered later that it was associated with age

• 100 billion neurons
• 100 trillion connections between these neurons

neurons communicate with each and carry out metabolism, and repair themselves --AZ disrupts these

• most common cause of dementia
• 7-9% of people of 65 have it, 35% of people over 85
• 4.5 mil in US and Canada have it
• 40% of total health care costs associated with neurological diseases

AD affects the surrounding families as well

• Symptoms--
• - impairment of memory and attention, language, and communication
• - judgement, personality changes , depression, visuo-spatial disorientation

• Signs--
• - motor and gait disturbances, extrapyramidal signs (poverty of movement, bradykinesias), sphincters, seizures

• occurrence-
• - usually late 50s or later

• etitiology-
• -- familial forms--10% of cases, earlier onset, have susceptibility genes
• -- sporadic--unknown cause, majority of cases

• -cortical atrophy
• -synaptic and neuronal loss
• -Neurofibrillary tangle (NFTs) with paired helical filaments
• -abnormal microtubules associated proteins
• -tau proteins
• -neuritic plaques with amyloid core
• -amyloid angiopathy

-hallmarks of AD

• plaques
• - dense deposits of protein and cellular material that accumulates outside and around nerve cells
• - amyloid precurser protein are embedded in the membrane, and are important for neuronal growth, survival and repair.
• - enzymes (secretase) cut the APP, frees beta amyloid, which tend to stick together which form the plaques

• tangles
• --twisted fibres that build up insides the nerve cell

• - decreased Ach in the cortex and hippocampus
• - Ach lives in basal forebrain nuclei, there is a net loss of Ach in the brain

• Treatments
• - trials to see if just giving more Ach worked--didn't
• - trials using Ach agonists--also didn't work, side effects
• - now--drugs that inhibit break down of Ach, but not a great fix because neural structures are still breaking down

• Cholinergic drugs
• - cholinesterase inhibitors (Aricept, Exelon, Reminyl)

• Noncholinergic drugs
• - possible treatments--amyloaid vaccine, secretase inhibitors, antiamyloid agents
• - unproven treatments--estrogens, NSAIDs, vasodilators, propentofylline

• Cholinergic drugs
• - cholinesterase inhibitors (Aricept, Exelon, Reminyl)

• Noncholinergic drugs
• - possible treatments--amyloaid vaccine, secretase inhibitors, antiamyloid agents
• - unproven treatments--estrogens, NSAIDs, vasodilators, propentofylline

Imaging--PET scans, injection with a compound that can cross BBB and stick to amyloid

• - fluctuating cognition with pronounced variation in attention and alertness (e.g. can be good one day and not the next)
• - visual hallucinations
• - Parkinsonian features (difficulty with movements)
• - treatment with cholinesterase inhibitors, atypical antipsychotics

- loss of pigmented neurons in the Substantia nigra in PD and Dementia with lewy bodies

more behavioural changes, personality changes

• - more common in females and at a younger age than AD
• - focal frontal and temporal loba atrophy
• - disinhibition, apathy, perseveration, mental rigidity and affective symptoms
• - Tau pathology most frequently observed
• - Familial forms--gene on Chromosome 17
• - no curative treatment

• accounts for 10-15% of dementias
• occurs stroke by stroke with progressive loss of function
• clinical features of stroke profile--hyptertension, diabetes
• can occur with neurodegenerative dementia
• CT scan can show multiple areas of cerebral infarction

treatment of risk factors to lower risk