Dementia and Alzheimer's Disease Flashcards
Why has dementia been “rebranded” as Major Neurocognitive Disorder in the DSM-5?
One reason is to reduce stigma, another is that dementia is widely accepted for older adults but is not very appropriate for younger adults who have cognitive problems.
What is the criteria for dementia?
A. Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition) based on:
1. Concern of the individual, a knowledgeable informant, or the clinician that there has been a significant decline in cognitive function; and
2. Substantial impairment in cognitive performance, preferably documented by standardised neuropsychological testing or, in its absence, another quantified clinical assessment.
B. The cognitive deficits interfere with independence in everyday activities (i.e., at a minimum, requiring assistance with complex instrumental activities of daily living such as paying bills or managing medications).
C. The cognitive deficits do not occur exclusively in the context of a delirium.
D. The cognitive deficits are not better explained by another mental disorder.
At least 50 different disorders can cause the deficits seen in MNDs including Huntingdon’s disease, Parkinson’s disease, syphilis, meningitis, AIDs, intracranial tumours and abscesses, dietary deficiencies, anoxia, inhalation/ingestion of toxic substances such as mercury, and so on.
What is Parkinson’s Disease characterised by?
PD is the second most common neurodegenerative disorder after Alzheimer’s Disease. It is found more often in men than in women, affects between 0.5-1% of people between 65-69, and 1-3% of people over 80 (Toulouse & Sullivan, 2008). Parkinson’s is characterised by motor symptoms such as resting tremors or rigid movements. The cause is loss of dopamine neurones in the substantia nigra, resulting in the inability to move in a controlled and fluid manner. Psychological symptoms manifest as depression, anxiety, apathy, cognitive problems, and even hallucinations and delusions (Chaudhuri et al. 2011). Over time, 25-40% of patients with PD will show signs of cognitive impairment.
What is Huntingdon’s disease characterised by?
A rare, relentless degenerative disorder affecting 1 in every 10,000 people. The illness begins in midlife, and is characterised by a chronic, progressive chorea. Subtle cognitive problems often predate the onset of motor symptoms by many years. These are no doubt due to progressive loss of brain tissue occurring as much as a decade before formal onset of the illness. Patients eventually develop dementia, and die usually within 10 to 20 years of onset. It is caused by a single dominant gene on chromosome 4 (the Huntingtin gene). There are no known effective treatments.
What is the defining characteristic of AD? Why can’t this be diagnosed? What is used instead?
Diagnosis is made after a thorough clinical assessment, but can only be confirmed after death with an autopsy. In a living patient, diagnosis is given by ruling out other potential causes of dementia by medical and family history, physical examination, and laboratory tests.
It is characterised by multiple cognitive deficits, not just memory problems. Deterioration is slow but progressive. In the earliest stages, AD involves minor cognitive impairment, such as difficulty in recalling recent events, make more errors at work, or take longer to complete routine tasks. In later stages, dementia becomes more evident, resulting in inability to function. Due to impaired memory, many patients have “empty” speech in which grammar and syntax remain intact, but vague and seemingly pointless expressions replace meaningful conversational exchange.
What is the progression of damage in the AD brain? What can this cause?
The temporal lobes are first to be damaged, meaning that the hippocampus is one of the first structures to be impaired (which is why memory loss is one of the early symptoms). Atrophy in the temporal lobes also explains delusions (Lyketsos et al. 2000). Persecutory delusions are dominant, but delusional jealousy is sometimes seen as well. Here, the person persistently accuses their partner of spouse (often of advanced age and physically debilitated) of being sexually unfaithful. One study of physically aggressive patients with AD found that 80% of them were delusional.
How can symptoms of AD be alleviated before death?
With treatment, including medication and the maintenance of a calm, reassuring, and unprovocative social environment, many people with AD show some alleviation of symptoms. However, the deterioration continues its downward course over a period of months or years. Eventually, patients become oblivious to their surroundings, bedridden, and reduced to a vegetative state. As resistance to disease is lowered, death usually results from pneumonia or some other respiratory or cardiac problem. The median time to death is 5.7 years from onset (Jalbert et al. 2008).
What are the risk factors for AD.
The rate of AD is estimated to double every 5 years after the age of 40 (Hendrie, 1998).
Outline and evaluate the causal factors for EOAD.
Three mutations have been implicated EOAD (Ballard et al., 2011). One involves the Amyloid Precursor Protein (APP) gene, on C21. APP gene mutations are associated with onset of AD between 55-60 years of age. The fact that a gene on chromosome 21 is interesting, as those with Down syndrome who survive beyond age 40 develop an Alzheimer’s-like dementia and show similar neuropathological changes.
Other cases of even earlier onset appear to be associated with mutations of presenilin 1 on chromosome 14 (PS1) and of presenilin 2 (PS2) on chromosome 1. These are associated with an onset of AD between 30 and 50 years of age (Cruts et al., 1998). These genes are autosomal dominant genes and will nearly always cause disease in anyone who carries them. However, these variants are extremely rare, and the three together account for no more than 5% of cases of AD.
Outline and evaluate the causal factors for LOAD.
The APOE (apolipoprotein) gene on chromosome 19 plays an important role in LOAD. This gene codes for a blood protein that helps carry cholesterol in the bloodstream. Three alleles of this gene have been implicated, and everyone inherits two of them, one from each parent. The APOE-E4 allele significantly enhances risk for late-onset disease. A person may inherit, zero, one, or two of these alleles, and their risk will increase correspondingly. Having two copies results in a sevenfold increase in a person’s chance of developing AD. The alleles differ in how efficient they are in clearing amyloid, APOE-E2 is most efficient (and so offers protection against AD) and APOE-E4 is least efficient. APOE-E3 is “neutral” (Karran et al. 2011). APOE-E4 (detected by a blood test) is overrepresented in all types of Alzheimer’s disease (Inc. early onset and late onset). ~65% of patients have at least one copy. However, many people who inherit the riskiest APOE pattern do not succumb to the disorder (only 55% by age 80, Myers et al. 1996). In addition, substantial numbers of MZ twins are discordant for AD (Bergen et al. 1993).
What is the theory as to why there is discordance in MZ twin rates.
Current reasoning is the interaction with other genetic factors and with environmental factors. Diet may be an important mediating variable (due to differences in prevalence across different parts of the world). Being overweight, having Type 2 diabetes, or not being physically active have also been implicated as risk factors. The associates with diabetes is particularly interesting because researchers have found that insulin levels are abnormally low in some of the brain areas that are most affected by AD.
Exposure to non-steroidal anti-inflammatory drugs such as ibuprofen may be protective and lead to a lower risk of AD.
People with more cognitive reserve (a concept combining education, occupation, and mental engagement) also seem to be at reduced risk.
Outline the causes and effects of amyloid plaques.
In AD individuals, neurones secrete beta amyloid much more quickly than it can be broken down and cleared away. Beta amyloid accumulates into plaques which are thought to interfere with synaptic functioning. This sets off a cascade of events that leads to the death of brain cells. Beta amyloid cells also appear to be neurotoxic, and amyloid plaques trigger local chronic inflammation in the brain and release cytokines that further exacerbate this process. APOE-E4 is associated with more rapid build-up of amyloid. In animal studies, stress appears to make this problem worse. Insulin may also play a role in regulating amyloid. Amyloid deposits can be present as many as 10 years before clinical signs of AD first appear. Amyloid plaques may block synaptic communication and cause immune system response. Unknown if cause of alzheimer’s or effect.
Outline the causes and effects of neurofibrillary tangles.
Neurofibrillary tangles are webs of abnormal tau (a protein) filaments within a nerve cell. In normal, healthy brains, tau acts like scaffolding, supporting microtubules in neurones and allowing them to conduct impulses. In AD, the tau is misshapen and tangled due to hyperphosphorilation, causing the neurone tube to collapse. The build-up of tau protein is believed to be accelerated by an increasing burden of amyloid in the brain (Shim and Morris, 2011), though it can occur independently.
Outline the causes and effects of cerebral atrophy.
Although there is widespread destruction of neurones in AD (particularly in the hippocampus), evidence suggests that among the earliest and most severely affected structures are a cluster of cell bodies located in the basal forebrain and involved in the release of acetylcholine (Schliebs & Arendt, 2006). The reduction in brain ACh activity in patients with AD is correlated with the extent of neuronal damage that they have sustained. ACh is incredibly important in memory, and the loss of its production cells makes a bad situation worse. Its depletion contributes greatly to the cognitive and behavioural that are characteristic of AD.
How can symptoms of AD be prvented?
r
