Stahl Chapter 12 Flashcards
All Cause Dementia ( p. 487).
. cognitive/neuropsychiatric symptoms that interfere with ability to perform usual activities
. decline from previous levels of functioning
. not attributable to delirium or a major psychiatric disorder
. cognitive impairment diagnosed through neuropsychological testing or patient informant
. cognitive impairment involves two of the following:
. impaired ability to acquire/retain new information
. reasoning impairment
. visuospatial impairment
. changes in personality or behavior
Four causes of dementia; p. 488
. alzheimer’s disease
. vascular dementia
. lewy body dementias
. frontotemporal degeneration dementia
FOR DIFFERENTIAL DIAGNOSIS INFORMATION LOOK AT TABLE ON PAGE 488.
Parkinson’s Dementia; p. 493
. Hypothesized to be neuronal degeneration and atrophy occurring in the thalamus, caudate nucleus, and hippocampus.
. Lewy body pathology is also found in neocortical areas.
. Severity of dementia in PD correlates with severity of a-synuclein as well as amyloid and tau pathology in limbic regions.
Parkinson’s Disease Dementia versus Lewy Body Dementia; p. 494
. Motor symptoms precede dementia in PDD by at lease one year
. If dementia occurs at the same time or precedes the onset of parkinsonism the diagnosis is LBD.
Alzheimer’s Disease; p. 489
. Two of the major pathological hallmarks seen in AD brain at autopsy are plaques composed of amyloid beta and neurofibrillary tangles composed of hyperphosphorylated tau protein.
Mixed Dementia; p. 496
. Dementia with only one pathology is the exception
. Most common is AD plus non-AD plus vascular pathology
. Second most common is AD plus vascular pathology.
Apolipoprotein E
. APOE is a protein that transports the cholesterol needed by neurons for synapse development, dentrite formation, longer term potentiation, and axonal guidance.
.APOE 2- appears to offer some protection from AD
. APOE3- allele is the most common and conveys a risk that falls between APOe2 and APOE4
. APOE4- allele results in a threefold increase in the risk of developing AD with only one copy.
. With two copies of APOE4 this leads to a tenfold increased risk of developing AD.
. 15% of the general population has APOE4 and 44% of the AD population has APOE4
Three stages of AD; p. 500
a. Presymptomatic Stage 1- This is the asymptomatic stage where neurodegeneration is silently started as amyloid-beta increases in the brain. The amyloid-beta is detectable using PET scan and radioactive neuroimaging racers. Additionally, CSF levels of amyloid-beta are low in stage 1.
b. Predementia/MCI Stage 2- There is a progression from asymptomatic amyloidosis to presentation of clinical symptoms of mild cognitive impairment (MCI). Neurodegeneration can be detected by elevated tau protein levels in CSF, atrophy on MRI and/or presence of neurofilament light in CSF or plasma.
c. Dementia Stage 3- The individual meets the diagnostic criterial for all cause dementia coupled with insidious (gradual) onset showing declining cognition over time and difficulty with learning and recall or with language, visuospatial or executive functioning. Neuro findings include positive biomarker evidence of brain amyloid-beta or downstream neuronal degeneration.
Dementia medication treatments; p. 503
. treatments target neurotransmitters in different brain circuits that hypothetically regulate the different symptoms in dementia.
. treatment is of symptoms rather than disease-modifying
Medications; p. 504
. Memory network:
.Namenda (memantine) and AChE inhibitors: acetylcholine and glutamate can be targeted by acetylcholinesterase (AChE) inhibitors;
. memantine is an NMDA antagonist
. Psychosis network:
.The psychosis of dementia can be targeted at the serotonin and dopamine nodes. Pimavanserin (nuplazid) is a 5HT2a antagonist approved to treat psychosis in PD.
. Agitation network:
. NE, 5HT, DA and GLU can be targeted to decrease agitation. NMDA antagonist desctromethorphan together with bupropion as well as brexpiprazole (Rexulti) are studied for their use in agitation in dementia.
p 509-510
. The progressive loss of neocortical and hippocampal neurons in dementia and receptor targets of cholinergic treatment are lost. Yet the most effective treatement is to boost cholinergic function by ceasing destruction of ACh by inhibiting enzyme acetylcholinesterase.
Cholinesterase inhibitors works by stimulating postsynaptic cholinergic receptors by increasing Ach levels with acetylcholinesterase inhibition. In other words cholinesterase inhibitors block acetylcholinesterase thus increasing ACh concentration in the synaptic cleft. This results in increased cholinergic activation and is thought to restore lost function of degenerated cholinergic neurons (Stahl p. 509). Even though in AD there is progressive loss of neocortical and hippocampal neurons across the stages (1-3), it is still thought that treatment of intermediate-term cognitive and memory issues in AD can stop/slow down destruction of ACh via boosting cholinergic functioning; this occurs by inhibiting the enzyme acetylcholinesterase.
More medications
. Aricept (donepezil)- a reversible, long actting, selective inhibitor of AChE without inhibition of BuChE (GI side effects)
. Exelon (Rivastigmine)- reverses itself over hours; intermediate acting and selective for AChE in cortex and hippocampus.
Glutamate; p. 515; 516; 520
. Thought to be released in excess as AD develops.
. memantine- reduces abnormal activation of glutamate and improves cognition and slows decline.
. memantine is an uncompetitive open channel NMDA receptor antagonist
Delusions and Hallucinations
. seem to be regulated by neuronal network that connects glutamate, GABA, serotonin, and dopamine.
. to decrease these psychotic symptoms, can block input of serotonin at 5HT2a receptors with pimaverserin.
Agitation in Dementia
. hypothesis is that there is deficiency in thalamic filtering of sensory input due to loss of top-down cortical inhibition and
. this results in motor and emotional agitation.
