Neuro: Alzheimer’s disease: Free MSRA Podcast

🧠🎯 MSRA DEEP DIVE: Alzheimer’s Disease (High-Yield Revision)

In today's episode, we break down one of the highest-yield topics in Neurology for the MSRA: Alzheimer’s Disease. This is your full, structured revision guide — perfect for both your exam prep and clinical understanding. 🚀

🔑 High-Yield Revision Summary

📌 Definition
• Progressive neurodegenerative disorder
• Causes dementia through memory loss, cognitive decline, behavioural changes
• Most common cause of dementia globally
💡 Mnemonic: "A for Alzheimer’s = Atrophy & Amyloid"

📌 Causes
• Abnormal protein accumulation:

• Beta-amyloid plaques (extracellular)

• Tau neurofibrillary tangles (intracellular)
  • Genetics:

• APOE ε4 allele (late onset risk factor)

• Rare familial Alzheimer’s: autosomal dominant (early onset)
  • Multifactorial: genetic, environmental & lifestyle interactions

📌 Risk Factors
• Non-modifiable:

• Advancing age (biggest risk factor)

• Family history (↑3.5x risk with 1st-degree relative)

• APOE4 gene

• Caucasian ethnicity
  • Modifiable:

• Diabetes, hypertension, obesity (especially midlife)

• Physical inactivity (up to 50% risk reduction with high activity)

• Smoking, lower education, social isolation

📌 Pathophysiology
• Progressive neuronal loss in hippocampus & cortex
• Amyloid plaques + Tau tangles → neuronal dysfunction
• Acetylcholine depletion contributes to memory impairment
• Neuroinflammation & oxidative stress accelerate degeneration

📌 Differential Diagnosis
• Other dementias:

• Vascular dementia

• Lewy Body dementia

• Frontotemporal dementia
  • Non-dementia mimics:

• Depression (pseudodementia)

• Hypothyroidism

• B12 deficiency

• Medications

• Normal Pressure Hydrocephalus (NPH)

📌 Epidemiology (UK Data)
• ~520,000 affected with Alzheimer’s in the UK
• Dementia: 1 in 14 people over 65
• Alzheimer’s accounts for ~two-thirds of all dementia cases
• Numbers increasing with rising life expectancy

📌 Clinical Features
• Early:

• Short-term memory loss

• Disorientation

• Word-finding difficulty

• Mood changes
  • Progressive:

• Executive dysfunction

• Self-care impairment

• Communication breakdown

• Behavioural disturbances (agitation, aggression)

• Wandering

📌 Diagnosis• Primarily clinical based on hx + collateral hx• Cognitive testing: MMSE, Montreal Cognitive Assessment• Neuroimaging: MRI (rule out stroke/tumour), PET/SPECT for metabolism• Bloods to exclude mimics: FBC, U&Es, Ca2+, TFTs, B12/folate• Mild Cognitive Impairment (MCI)

📌 Management (UK NICE-based)• Pharmacological:

• Acetylcholinesterase inhibitors (AChEIs): donepezil, rivastigmine, galantamine

• NMDA antagonist: memantine for moderate-severe disease• Non-pharmacological:

• Cognitive stimulation therapy

• Memory aids, structured support

• CBT for depression/anxiety

• Behavioural therapies: aromatherapy, music, pet therapy, exercise
  • Supportive Care:

• Dementia

Episode Transcript

(00:00):
Welcome to the Deep dive. Today we're getting straight
into it. We're looking at a specific
condition, Alzheimer's disease. We've got a set of, well,
basically MSRI revision notes here and we're going to pull out
the high yield stuff. The goal is to give you a really
clear, structured understanding.Think of it as a sorting through
the key points for revision, or just, you know, getting properly

(00:20):
informed. Exactly.
We'll be covering it all based on these notes.
What it is, the causes? The risks?
What's happening in the brain? Differentials.
How common it is? Right symptoms, diagnosis,
management, prognosis, complications, the whole
picture, but broken down so it makes sense.
OK, let's start right at the beginning.
The definition. What do the notes say
Alzheimer's actually is? So fundamentally, the notes

(00:41):
define it as a progressive neurological disorder.
It affects the brain, leading tomemory loss, cognitive decline,
changes in behaviour too, and a really critical point they make
right away. It's the most common cause of
dementia. OK, right.
So that's key, isn't it? Alzheimer's leads to dementia,
but they're not identical. Precisely.
The notes are clear. Dementia is that broader term.

(01:04):
It's a chronic, progressive, irreversible decline in
cognitive function. Alzheimer's is the specific
disease causing that decline in most cases.
And which cognitive areas does it hit?
The notes must list. Those they do, it's, it's quite
wide-ranging memory, obviously language, abstract thinking,
motor skills, visuospatial skills.

(01:25):
So understanding space around you.
Also executive function like things like planning, problem
solving and personality, social behaviour, it really impacts
across the board. Wow.
And physically inside the brain.What's the script?
Well, there's progressive degeneration of the cerebral
cortex. That's the outer layer.
It leads to widespread atrophy, basically shrinkage.

(01:45):
And the notes highlight the key players, these abnormal protein
deposits. You got the amyloid plaques and
then neurofibrillary tangles which are made of Tau protein.
The plaques and tangles, you always hear about those.
Exactly, plus they mentioned reduced production of
acetylcholine. That's a neurotransmitter really
vital for memory and learning. So these protein buildups are
actually damaging the cells or stopping them working properly.

(02:07):
That's the idea, yeah. They disrupt how neurons
function and communicate. And something quite stark, the
notes point out, this neurodegeneration, this damage
might actually be starting, you know, a decade or even more
before symptoms become obvious. A whole decade?
Wow. Yeah.
And over time, it leads to that irreversible global brain
function impairment and reduced intellectual ability.

(02:29):
OK, so we know what it is and roughly what's going wrong
physically. But why?
What about the aetiology? The causes?
The notes really stress that it's complex.
There isn't one single 'cause wecan point to.
It's seen as this complicated interplay.
Genetics, environmental factors,lifestyle choices, they all seem
to feed into it. But the core mechanism, the

(02:50):
notes, bring it back to that abnormal protein accumulation we
just talked about, the beta amyloid forming plaques outside
the neurons and the Tau protein clumping into tangles inside
them. These are really central to the
disease process described. And genetics plays a role beyond
just, say, having it run the family specific genes.
Yes, definitely. The notes mentioned specific
gene mutations can increase susceptibility, and of course

(03:12):
family history itself is a big factor.
Having a first degree relative, a parent or sibling with
Alzheimer's significantly bumps up the risk.
Right, Let's talk more about that risk.
Who are the notes saying is morelikely to develop Alzheimer's?
They break it down quite neatly into non modifiable factors, the
ones you can't change and modifiable ones which you
potentially can influence. So non modifiable.

(03:33):
Top of the list is advancing age.
It's the biggest single risk factor.
Caucasian ethnicities also mentioned family history.
Like we said, the notes actuallyput a number on it 3.5 fold
increased risk if a first degreerelative is affected.
And then there's a specific genevariant, apolipoprotein E4 or
APO E4 that's flagged as an important genetic risk factor,

(03:55):
particularly for the late onset sporadic type, which is the most
common form. OK, age and genes, things we
can't control. What about the modifiable side?
What levers can potentially be pulled?
Yeah, this is where it gets quite hopeful.
Potentially, the notes suggest these modifiable factors might
contribute to as many as 1/3 of cases.
So things like cardiovascular risk factors are big here.

(04:16):
Like blood pressure, diabetes. Exactly.
Diabetes, hypertension, obesity,especially obesity and midlife,
the notes say that increases risk by about 60%.
And then lifestyle habits, smoking, physical activity
levels, diet, and interestingly,how mentally and social active
you are. Physical activity makes a
difference. A big difference, apparently.

(04:38):
The notes quote a potential 50% risk reduction with high
physical activity. That's quite something.
And the idea is that keeping your brain busy, cognitive
stimulation, social interaction,intellectual pursuits, even
higher education, it seems to build up what they call
cognitive reserve. Like a buffer?
Sort of, yeah. More capacity to cope with the
underlying brain changes before symptoms show.

(04:58):
Though it's worth noting the notes do mention the link
between smoking and Alzheimer's risk is presented as somewhat
unclear in the material they reviewed.
It really shows how connected everything is.
Heart health. Lifestyle Brain health.
OK, let's go back to the brain itself, the pathophysiology.
How do those risk factors translate into the actual

(05:19):
damage? So the core process described as
this progressive loss and, well,degeneration of brain neurons,
it happens particularly in areasvital for memory and thinking,
like the hippocampus and the cortex.
And this neuron loss is intrinsically linked to those
abnormal proteins forming deposits, the beta amyloid
plaques building up between the cells and the Tau tangles

(05:40):
forming inside them. So it's the plaques and tangles
causing the damage, or a result of it, or both?
It's complex, likely both contributing in a cycle.
These deposits, along with inflammation and oxidative
stress, which is like cellular damage from unstable molecules.
They basically disrupt how braincells work and talk to each
other. Leading to the symptoms we
eventually see. Exactly that disruption is what

(06:00):
primarily effects memory, cognition and behaviour,
according to the notes. They also list inflammation,
oxidative stress and impaired neurotransmitter signalling,
like with acetylcholine, as key contributing factors to the
overall dysfunction. OK, now if someone comes in with
memory issues, confusion, it's not automatically Alzheimer's.
How do you tell it apart from other things?

(06:22):
What's in the differential diagnosis section?
This is really crucial because the notes highlight that telling
early Alzheimer's apart from just, you know, normal
age-related memory slips can be tricky initially.
So they list other types of dementia.
You have to consider things likevascular dementia often linked
to strokes or blood vessel problems, Lewy body dementia

(06:43):
which often has Parkinson's likefeatures and visual
hallucinations, front or temporal dementia which tends to
hit personality and language earlier, and dementia associated
with Parkinson's disease itself.They can look similar sometimes.
But aren't there also conditionsthat aren't dementia at all that
can look like it? Yes, absolutely.
And this is perhaps even more critical because some might be

(07:03):
treatable notes call these the mimics.
Depression is a big one. Could cause what looks like
dementia, sometimes called pseudo dementia.
Also thyroid problems, vitamin deficiencies, particularly B12,
side effects from certain medications can cause confusion,
normal pressure, hydrocephalus or MPH, and hypothyroidism,
again specifically mentioned that's.
Quite a list of things to rule out.

(07:24):
It is, and the notes emphasise the diagnosis isn't simple.
It involves a really thorough clinical evaluation, detailed
cognitive tests, brain scans like MRI or PET, and lab tests,
all designed to piece the puzzletogether and differentiate
Alzheimer's from other dementiasand these important mimics.
And how common is it? What do the epidemiology notes
say, particularly for the UK? Well, it's framed as a major

(07:47):
public health issue. Unsurprisingly is much more
common in older people. The risk climb steeply with age.
The UK figures cited are around 520,000 people affected
specifically by Alzheimer's and thinking more broadly about
dementia. The notes say about one in 14
people over 65 in the UK has some form of dementia.
And Alzheimer's is the biggest chunk of that.

(08:08):
Yeah, roughly 2/3 of all dementia cases are thought to be
Alzheimer's. It affects both men and women.
And, you know, as people are living longer, the overall
number of cases is expected to keep riding.
The notes also make a distinction between sporadic
Alzheimer's. That's the common type occurs
worldwide. Complex causes and familial

(08:29):
Alzheimer's that one's rare, caused by specific inherited
gene mutations, usually starts much earlier in life and follows
an autosomal dominant pattern. OK.
So we know it's common. What does it actually look like
in a person? What are the typical clinical
features described in these notes?
Right, the symptoms, the classicearly sign is usually
progressive memory loss, especially for recent stuff, for

(08:51):
getting conversations, appointments, that kind of
thing. Then you start seeing difficulty
with problem solving, planning things out, confusion, maybe
getting lost in familiar surroundings, disorientation.
Language problems too. Yes definitely.
Difficulty finding the right words, following conversations,
mood and behaviour changes are common.
Maybe becoming withdrawn, irritable, anxious or depressed.

(09:13):
Losing interest in hobbies or social activities.
As things progress difficulties emerge with basic self-care.
Bathing, dressing, eating, communication becomes more
challenging. Decision making gets harder.
Managing day-to-day life becomesa struggle.
The notes also add things like personality changes, sometimes
agitation or a tendency to wander.
The key thing is it's progressive.

(09:33):
These symptoms get worse over time, leading to really
significant impairment. So with that picture in mind,
how is the diagnosis actually confirmed according to these
notes? The notes state it's primarily A
clinical diagnosis. It's based on identifying those
characteristic patterns of cognitive decline, short term
memory, language, visual spatialskills, praxis which is carrying

(09:55):
out learned movements and crucially, it's a gradual
decline over months or years. Something really highlighted is
vital is getting a collateral history.
That means talking to family members or close friends.
They often notice the changes first or can give crucial
context. The diagnosis process often
kicks off because a relative raises concerns.
So it's not just testing the patient in isolation.

(10:16):
No, definitely not. That wider perspective is key.
The notes then outline specific criteria for probable
Alzheimer's disease. You need dementia confirmed
clinically or with tests. Problems in at least two
cognitive areas. A slow insidious start over
month years with worsening. No disturbance of consciousness
and no other systemic or brain disorder that fully explains it.

(10:39):
Possible Alzheimer's might be diagnosed if the onset or course
is a bit unusual or if there seem to be other causes mixed in
and they also cover mild cognitive impairment or MCI due
to Alzheimer's. This is like a pre dementia
stage. There's concern about cognitive
change. Some objective evidence of
impairment, but the person is still functionally independent.
They don't meet the full dementia criteria yet.

(11:00):
They mentioned newer terms like mild neurocognitive disorder
from DSM 5/2. What about tests?
What investigations back this up?
OK investigations typically usedin the UK.
According to the notes, a full medical history and physical
exam are standard. Cognitive assessments like the
MMSE mini Mental State exam are used for screening, but the
notes stress MSE is a screen. It's not diagnostic by itself.

(11:23):
More detailed neuropsychologicaltesting might be done.
And brain scans. Yes, brain imaging MRI is often
used first, mainly to rule out other things like strokes,
tumours or look for signs of vascular changes.
Peat or speck scans can show specific patterns of brain
metabolism reduction typical of Alzheimer's, but they aren't
always essential for the diagnosis.

(11:43):
And finally, lab tests are crucial to exclude those mimics.
These like a full blood count, electrolytes and kidney
function, U and ES, calcium, thyroid function tests, checking
B12 and foliate levels, hematinix, and maybe an ESR for
inflammation. A chest X-ray or urine test
might be done if an infection suspected as that can worsen
confusion. OK, diagnosis made.

(12:04):
What about management? The notes say no cure, so what's
the focus? You're right, that's the clear
message. No cure currently, so management
is all about supportive care, trying to optimise cognitive
function as much as possible, manage symptoms and maintain
quality of life for both the person and their family.
It's described as a multi pronged approach.
There's medication, there are non pharmacological

(12:27):
interventions, crucially supportservices for everyone involved
and links with specialist dementia services and community
support. Let's talk about the medications
first. What's used?
The notes list the main approveddrugs.
Firstly, the acetylcholinesterase inhibitors,
often called AC inhibitors. Examples are done PSL,
revastigmine, galantamine. They boost levels of
acetylcholine. The other main one is mementime.

(12:49):
It works differently on NMDA receptors.
The notes suggest these drugs can provide some clinical
benefit, help with symptoms for maybe six months up to a couple
of years. Do they mention side effects?
Yes, common ones listed are GI upset like nausea or diarrhoea.
A rash can occur with a revastigmine patch and memantine
can cause drowsiness or dizziness.

(13:10):
In terms of guidance, ATE inhibitors are usually
recommended. First line memantine tends to be
from moderate to severe stages, or if someone can't tolerate the
ECE inhibitors. It can also be added on top of
an AC inhibitor in moderate to severe cases.
Starting memantine without trying an AC inhibitor first
usually needs specialist input. And beyond medication, the non

(13:32):
pharmacological side. Hugely important according to
the notes. Things like structured group
cognitive stimulation programmesare recommended, especially for
mild to moderate dementia. Memory aids and strategies can
help. CBT might be useful if there's
coexisting depression or anxiety.
For managing challenging behaviours or anxiety and
agitation. The focus is often on non drug
approaches first. Things like aromatherapy, music

(13:54):
therapy, pet therapy, exercise are mentioned.
Getting volunteers involved, keeping people engaged.
And thinking longer term palliative care must be crucial.
Absolutely vital. The notes stressed the need for
comprehensive support as the disease progresses, including
good access to palliative care. They touch on difficult aspects
like nutrition, encouraging oralintake but specifically stating

(14:15):
PEG feeding. Tube feeding isn't recommended
in severe dementia. Decisions about withholding
nutrition need to follow legal and ethical frameworks.
Managing fevers, deciding about antibiotics palliatively.
These are individual decisions focused on comfort and
resuscitation decisions. Very complex, accounted by
advanced directives, family views, frameworks like the

(14:36):
Mental Capacity Act and Resuscitation Council guidance
all needs careful discussion andclear documentation.
What's the general outlook then?The prognosis according to these
notes. It's described as variable,
depends on things like age and onset, general health, how
quickly the disease progresses for that individual.
But it's consistently described as chronic and progressive.
It leads to a gradual decline. The notes give an average life

(14:57):
expectancy after diagnosis of around 48 years, but they do add
that some people live much longer, potentially up to 20
years. So it's quite a range.
So it varies a lot person to person.
It does. Treatment, response, the quality
of care and support. These things influence outcomes
too, but ultimately the note state it leads to significant
impairment, loss of independence, and the need for

(15:18):
full time care eventually. And finally, what about
complications? What problems can crop up along
the way? As the disease gets more
advanced, various complications are common.
Increased vulnerability to infections is a big one.
Pneumonia UTI's are frequently mentioned, often due to reduce
mobility or difficulty with hygiene.
Falls and injuries are another major concern due to problems

(15:39):
with balance, coordination, maybe judgement.
Malnutrition and dehydration canhappen if eating and drinking
become difficult. Medication mismanagement is a
risk too. Behavioural issues like
agitation or aggression can be very challenging and the
difficulties with basic activities of daily living,
bathing, dressing, eating becomemore pronounced.

(16:00):
And the notes explicitly mentionthe significant burden on
caregivers, the psychological distress they can experience.
So managing complications is about prevention where possible,
monitoring closely and addressing symptoms promptly to
keep the person safe and comfortable while also
supporting the carers. Wow.
OK, we've covered a huge amount.They're digging right into these
MSRA notes. From the basic definition, the

(16:22):
brain changes right through to complications and prognosis.
It's clearly a condition with a massive impact.
It really is. I think understanding that core
pathology, you know, the plaquesand tangles, the neuron loss and
how that creates such a wide range of symptoms is really
fundamental. And remembering those mimics the
importance of ruling out treatable causes.
That's such high yield stuff foranyone revising or working in

(16:45):
healthcare. Yeah.
And I think what also comes through strongly from the notes
is the journey. It's not just about the person
diagnosed, but their whole family, their caregivers.
That emphasis on broad support beyond just the medical
treatment really hits home. It does.
And maybe a final thought for you listening, building on that,
think about that challenge. We touched on that often grey

(17:07):
area between what might be considered normal ageing and the
very earliest subtle signs of Alzheimer's.
It really raises questions aboutawareness, about when to seek
advice, when to push for investigation.
Something worth mulling over now.
If you are revising and found this useful and you're looking
for more high yield resources structured like this, do check
out pastthemsra.com. And there's also free m-sra.com

(17:29):
for more resources. Thanks so much for joining us
for this deep dive into the notes on Alzheimer's disease.
We really hope breaking it down this way has been helpful for
your understanding.