Alzheimer's and Dementia

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What is ageing?
The process of growing old
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In those that are healthy there is no?
Underlying disease, there's just a decline in cognitive ability due to ageing e.g. reduction inability to perform every day functions, make important decisions and live independently
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What are age related cases?
Dementia, wherein a disease causes progressive deterioration of the cognitive functions
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Park et al (2002)
Long term memory, problem solving, novel reasoning, behavioural speed decline over time; world knowledge is preserved
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Ritchie et al (2016)
Lothian Birth Cohort, longitudinal study from school years to old age, found deficits in visuospatial ability, processing speed and verbal memory
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Christensen (2009)
Canberra longitudinal study, cognitive speed and memory performance declined with age but crystallised abilities remained largely intact for those who survived for the long term follow up
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What was the evidence?
Poor health, fewer years of education, lower activity, the presence of the APOE E4 allele, and blood pressure predicts faster cognitive decline
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Hedden and Gabrieli (2004)
robust declines in the ability to form new episodic memories Semantic memory and short-term memory show remarkable preservation across most of the adult lifespan, with declines occurring only very late in life
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What is relatively unaffected by ageing?
Autobiographical memory, emotional memory and implicit memory are relatively unaffected by ageing
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What is the individual variation that contribute to cognitive function?
Genes, low birthweight, lower childhood intelligence, life-style factors – smoking, obesity, environmental toxins, cardiovascular disease – leads to increased cognitive ageing and increased risk of dementia
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Colcombe et al (2011)
aerobic exercise training increases brain volume, in both gray and white matter regions, (measured by fMRI) in ageing humans – cardiovascular fitness is associated with the sparing of the brain tissue in ageing humans
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What is the gross changes in the brain?
Decreased size - starts about the age of 30, the brain start to shrink, different areas decrease in different ways
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What is the minimal reduction?
Primary visual cortex, entorhinal cortex
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What is the large amount of reduction?
Caudate nucleus, lateral prefrontal cortex, cerebellar hemispheres, hippocampus, flattening of cortical surface - reduction in the surface area
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What are the neuroanatomical changes?
loss of neurons and changes in neuronal size. Altered dendritic processes – dendritic branches detract and hence there is a loss of connections
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What are the neurotransmitter changes?
REduction in the efficacy of neurotransmitter signalling, due to changes in the receptors, leads to an increase in depression and memory performance
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Bishop et al (2010)
suggested that this may be due to a disruption of myelinated fibres that connect neurons in different cortical regions
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Where is neuronal loss minimal?
Most cortical regions of the normal ageing brain, changes in the synaptic physiology of ageing neurons may contribute to altered connectivity and higher order integration
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What is suggested?
Degree of disconnection between brain areas that normally function together in young adults
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Bishop et al (2010)
young and old ppts, scanned them as they completed a task. In the young ppts, there’s a range of activity in different areas, suggesting a network connection; in the older ppts, there’s activity in one specific location, lack of connectivity in tasks
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O'Sullivan et al (2001)
Proposed the disconnection hypothesis
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What is the disconnection hypothesis?
decline in normal aging emerges from changes in functional integration between systems of brain areas in addition to dysfunction of specific gray matter areas
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What is Dementia?
It is not a specific disease
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It's an overall term that describes what?
A group of symptoms associated with a decline in memory or other thinking skills severe enough to reduce a person's ability to perform everyday activities
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How much do Alzheimer's disease account for cases?
60-80% of cases
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What is dementia?
A syndrome not a disease. It's a group of symptoms that affects mental cognitive tasks such as memory and reasoning. It is an umberella term
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How much of the population suffer from dementia
1% of the population
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What does it increase to?
18-85% population suffer dementia by age of 85
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Abbott, 2011
There are multiple different types of dementia with Alzheimer's being the most common
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What is the first classification of dementia?
Cortical Vs subcortical
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What is cortical dementia?
Primarily effects the cerebral cortex e.g. AD
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What is subcortical dementia?
Effects white matter, neuronal connections between cortical areas and gray matter structures below the cortex e.g. parkinson's disease
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What is progressive dementia?
ALL dementias that result from a disease process
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What is static dementia?
result from a brain injury, over-ingestion of neurotoxic substance (e.g. alcohol) or infection (e.g. herpes encephalitis
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What is reversible disease?
Static are often reversible: a true reversible dementia = patient must show dementia in absence of delerium
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What is delirium?
transient cognitive problem associated with an acute confusional state, sometimes confused with dementia, usually has a quick onset and can be treated by changing medications or drug dose
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What is the biological assessment for dementia?
Brain Imaging – CT, MRI, PET, can see changes in brain structure, glucose metabolism and activity  Neurochemical Assessment – amount of neurotransmitter, metabolites
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What is the psychological assessment?
Clinical Interviews  Psychological Tests – standard tests of different functions e.g. intellect, memory, learning, language and executive function
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Alois Alzheimer (1901)
Working with Kreaplin in Germany, described a case of a 51 year old woman (Auguste D) who had profound cognitive and behaviour impairments
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he took her post mortem brain and drew what abnormalities?
her brain and found unusual formations and this was the first suggestion that these symptoms were related to the brain
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Riedel et al (2016)
Higher incidence of Alzheimer's in females after 75 years
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Episodic memory
• Variety of cognitive processes that test episodic memory performance (e.g. free recall, recognition, paired-associate learning) in different modalities (e.g. auditory, visual, olfactory)
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What is episodic memory ?
• Ineffective consolidation or storage of new information, Autobiographical memory (times, places, emotions, contextual knowledge), Facts, data, or events we can recall at will
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What is the hippocampus important for?
Memory, pre-frontal cortex important for control of memory: retrieval, working memory
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Backman et al (2001)
looked at free recall and recognition of words, short term memory digit span, then looked to see how many were diagnosed with AD 3-6 years later
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Those with AD performed how?
More poorly both 3 and 6 years before diagnosis on both recall and recognition (No difference in STM). Shows selective impairment of episodic memory before the diagnosis of AD
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What is the idea consistent with?
The idea that early changes in the hippocampal complex play an important role in the memory deficit, and this occurs early
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What is language and semantic knowledge?
Object naming - words/pictures categorised, semantic memory, temporal, frontal and parietal association cortices
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What is the Cambridge semantic memory test?
6 categories: animals, birds, fruits, household items, tools, vehicles and category fluency, naming, word-to-picture matching, picture sorting, word sorting association test - object vs target object
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Martin (1983)
AD and controls, production (naming and fluency) and comprehension of single words and semantic knowledge (vocabulary and similarities subtests of the WAIS) tested. AD = naming and fluency abilities were correlated and impaired
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What does this suggest?
AD may lead to a specific disruption in semantic knowledge – characterised by a difficulty in differentiating between items within the same semantic category
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What are executive functions, working memory and attention?
• Retrieving memory from our long term store and using it • Mental manipulation of information, concept formation, problem solving, cue-directed behaviour
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What is the test used for EF?
Wisconsin card sorting task
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What is this?
 Question: what’s the rule? E.g. shape of the object, colour of the object, number, location etc.  Change the rule and it becomes harder to change your sorting
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Perry and Hodges (1999)
attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions
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Perry and Hodges (1999)
it appears that divided attention and aspects of selective attention, such as set-shifting and response selection, are particularly vulnerable while sustained attention is relatively persevered in the early stages
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Chiu et al (2004)
executive function problems are associated with getting lost behaviour in early AD, mental difficulties in choosing a turn
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Visuospatial abilities
Visual search tests (simple/conjoined feature search, how quickly you can identify a target with an increasing amount of distractors) • Deficits in AD patients correlate with disease severity?
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Sunderland et al (1989)
clock drawing task, a measure of visuospatial ability in AD, tested the usefulness of this measure, found high significant correlations between mean score of clock drawings (by 6 independent observers) and AD severity
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Johnson et al (2012)
Compared to huge dataset of age-matched control
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Structural MRI
Progressive hippocampal atrophy
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Functional MRI
Changes in activation during encoding, is there the same levels
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PET
glucose metabolism (hypo-metabolism) reduction in metabolism, reduce in the demands for glucose, meaning less activity
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Hedden and Gabrieli (2004)
hippocampal volume declines are less apparent during normal ageing. By contrast, pathological processes, such as those that accompany Alzheimer's disease, severely affect hippocampal regions
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What area is particularly damaged?
, entorhinal cortex, which serves as an important relay between the prefrontal cortex and the hippocampus, is disproportionately affected by pathology
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What are the differential patterns of age related changes in the prefrontal cortex?
hippocampus indicates a two-component model of cognitive ageing, with normal ageing primarily affecting prefrontal areas, and pathological ageing affecting medial temporal regions
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Schuff et al (2009)
MRI study, found hippocampal volume loss over 6 months and accelerated loss over 1 year, increased rates of hippocampal loss were associated with presence of the APOE allele E4 gene
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Thompson et al (2004)
longitudinal MRI study, mapped changes across time, maps of gray matter loss showed the loss spreading from temporal and limbic cortices into frontal and occipital brain regions, sparing sensorimotor cortices
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What are these deficits correlated with
progressively declining cognitive status
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Wang et al (2005)
functional connectivity between the right hippocampus and a set of regions was disrupted in AD:
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Such as what?
medial prefrontal cortex, ventral anterior cingulate cortex, right inferotemporal cortex, right cuneus extending into precuneus, left cuneus, right superior and middle temporal gyrus and posterior cingulate cortex
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This disrupted the what?
hippocampal connectivity to the MPFC, vACC and PCC provides support for decreased activity in “default mode network” – a large scale brain network of interacting brain regions, involved in memory
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AD is a disease that affectS?
millions of people and costs a lot of money in helping those with the disease
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What do drug treatments not do?
Work well and have bad side effects
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Hard to improve symptoms when there have already been changes in the brain so it is best to?
catch them early (perhaps link to Mild Cognitive Impairment, a slowly developing memory impairment, who are 3 times at risk of developing dementia – although some don’t and whose symptoms decline over time
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Oh et al. (2016)
• Neuroimaging allowed us to understand the changes that occur, also looked at amyloid deposition and trying to develop this as a biomarker to detect early signs and as a measure of treatment success
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In those that are healthy there is no?

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Underlying disease, there's just a decline in cognitive ability due to ageing e.g. reduction inability to perform every day functions, make important decisions and live independently

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What are age related cases?

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Park et al (2002)

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Ritchie et al (2016)

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