Episode 23: Alzheimer’s Disease: Diagnosis, Research and Care

00:00:02: Welcome to another episode of Ph.Divinem Beyond The Love!

00:00:24: Today we'll explore the fascinating war on Alzheimer's disease, its symptoms, genetics, biomarkers and new therapies.

00:00:32: Let us begin!

00:00:41: Alzheimer's Disease affects millions people worldwide as a huge impact not only on patients but also in families, caregivers or healthcare systems.

00:00:52: In recent years scientific research has made a huge progress in understanding how the disease develops, how it can be diagnosed earlier and how new therapies may slow its

00:01:04: progression.

00:01:05: Today we discuss first clinical aspects of Alzheimer's disease

00:01:09: then will explore genetic factors involved with the disease

00:01:15: And finally we'll focus on diagnosis biomarkers Currently being studied in specialized centers, such as our institute.

00:01:26: The Institute of the Science and Neurology of Bologna.

00:01:36: Hello everybody!

00:01:37: We are Erika

00:01:39: Andrea Giannicole

00:01:41: All PhD students from the University

00:01:43: of Bologne

00:01:44: And we work at Valaria Hospital... ...the main neurological center in Bolognia.

00:01:49: Now let's get started with a first question What people hear about Alzheimer's?

00:01:56: They immediately think about memory loss.

00:01:59: But medically speaking, what kind of disease is it?

00:02:03: Good question!

00:02:05: Alzheimer's disease is a progressive neurodegenerative disorder.

00:02:09: We can say that this means that neurons in the brain gradually became damaged and die over time.

00:02:15: It also is one common cause for dementia especially among older adults.

00:02:22: Dementia refers to a group of symptoms affecting memory reasoning, language and daily function.

00:02:30: And what are usually the first signs of this disease?

00:02:35: Well, the earlier symptoms is generally short-term memory loss.

00:02:40: Patients may forget for example recent conversations or repeat same questions several times so misplaced objects very frequently.

00:02:50: At first these symptoms might seem armless because Occasionally, forgetfulness is common during hashing.

00:02:57: However in Alzheimer's disease the memory problems progressively interfere with everyday life.

00:03:02: But

00:03:08: Giannicole just tell me doesn't Alzheimer's affect only memory?

00:03:10: No I don't!

00:03:10: As this diseases progresses many other cognitive functions become impaired.

00:03:15: Patients may develop language difficulties orientation problem and reduce original abilities.

00:03:22: Simple daily activities such as cooking, driving or managing money can become difficult.

00:03:28: Behavioral and emotional changes are also common.

00:03:33: Moreover patients may be anxious depressed apathetic irritable confused.

00:03:41: What happens biologically inside the brain?

00:03:44: Well

00:03:45: that's a very interesting point.

00:03:47: There are these two abnormal proteins, which accumulate in the brain.

00:03:52: Beta amyloid and tau.

00:03:53: Now beta-amyloid forms plaques between neurons while tau forms tangles inside the neurons.

00:04:01: And this abnormalities disrupt communication between brain cells and eventually lead to neuronal death.

00:04:08: Indeed one of first brain regions affected is the hippocampus Which is essential for memory formation.

00:04:16: How do doctors begin evaluating a patient with suspected Alzheimer's disease?

00:04:22: According to our diagnostic pathway and according the protocols used in other specialized dementia centers, diagnosis starts with complete clinical assessment.

00:04:35: Doctors like me collect patients' medical history then also interview family members because you know relatives often notice cognitive changes before their patients does.

00:04:46: Neurological examinations and cognitive screening tests are then performed to evaluate memory, language orientation and attention.

00:04:56: I was wondering when comes to Alzheimer's disease which cognitive test is commonly used?

00:05:01: Well one of the most common use tools is the minimental state examination.

00:05:09: it also the easiest one but specialized centers may more extensive neuropsychological evaluations to distinguish between normal ageing, mycodity impairment and dementia.

00:05:23: These tests are considered essential according to Italian regional national international guidelines

00:05:30: And Zanicola.

00:05:31: what about blood test?

00:05:33: Are they also part of the diagnostic process?

00:05:36: Yes for course.

00:05:37: Before diagnosis of Alzheimer's disease doctors must exclude other possible causes of cognitive decline.

00:05:44: Routine blood tests help identify thyroid disorders, vitamin deficiencies, infections, metabolic disease or other medical conditions that may mimic dementia symptoms.

00:05:55: In fact what role does brain imaging play?

00:06:01: We can say it nowadays.

00:06:03: brain imaging is extremely important.

00:06:06: MRI scans are recommended because they help identify brain atrophy and exclude other neurological conditions such as strokes, tumors or other cycles.

00:06:15: It can also reveal the shrinkage of the hippocampus which is very common in Alzheimer's disease.

00:06:22: So it is correct to say that Alzheimer's progress in stages?

00:06:26: Yes we can divide a disease into three main stages.

00:06:31: In the early stage symptoms are mild and patients often still independent.

00:06:37: In the middle stage, confusion or memory problems become more severe And assistance with daily activities may be necessary.

00:06:45: in the late stages, patients lose much of their independence and often require full-time care.

00:06:59: Okay we've seen how doctors evaluate symptoms and conflict decline

00:07:04: but

00:07:04: Why do some people develop Alzheimer's disease while others don't?

00:07:09: Is genetics involved?

00:07:11: and how important is genetics in Alzheimer's Disease?

00:07:16: It's really important.

00:07:18: Genetics plays a major role, although not all forms of Alzheimer's are inherited the same way.

00:07:26: Scientists distinguish between familial Alzheimer's diseases.

00:07:32: Andrea, can you explain better?

00:07:34: what do you mean for familial Alzheimer's disease?

00:07:37: Familial Alzheimer is a rare inherited form of the disease that often appears before age over sixty-five.

00:07:45: It is linked to pathogenic variants in genes such as APP, PSEN one and PSEN two.

00:07:53: These variants increase production beta amyloid leading to earlier diseases onset.

00:07:58: And so,

00:08:01: what happens if doctors suspect genetic form of Alzheimer's?

00:08:07: In specialized centers like ours in Bologna selected patients may undergo molecular genetic analysis but Andrea can tell more about that.

00:08:15: Advanced techniques such as next generation sequencing and mutagen panels can identify pathogenic variants associated with hereditary dimensions.

00:08:26: Genetic counseling is extremely important before and after testing because these results may have psychological implications.

00:08:36: Okay, so this was for the genetic form but what about more common sporadic forms?

00:08:41: Sporadic Alzheimer's are much more complex right?

00:08:45: Yes!

00:08:46: The strongest known genetic risk factor is the APOE Epsilon IV variant.

00:08:52: People carrying this variant have a higher risk of developing Alzheimer's disease, but it does not guarantee that they will become ill.

00:09:01: Environmental and lifestyle factors are also very

00:09:04: important.

00:09:05: Andrea can you tell me which lifestyle factors influence the risk of Alzheimer's diseases?

00:09:12: Cardiovascular health is extremely important.

00:09:15: Hypertension, diabetes, obesity, smoking lack physical activity and poor sleep are associated with increased dementia risk.

00:09:25: On the other hand, exercise has nutrition social interaction and cognitive stimulation may help protect brain function.

00:09:35: But our researcher discovering new genetic mechanisms involved in Alzheimer's

00:09:40: right?

00:09:41: Yes of course.

00:09:42: modern research is increasingly focused on inflammation an immune system activating the brain.

00:09:49: The Bologna EX laboratories are also involved in studying molecular biomarkers and inflammatory pathways associated with neurodegenerative diseases.

00:09:58: This research may eventually lead to more personalized therapies.

00:10:04: But could genetics help predict Alzheimer's disease before symptoms appear?

00:10:10: Possibly yes.

00:10:11: Scientists hope that combining genetic biomarker and imaging techniques could identify high risk individuals many years before symptoms emerge.

00:10:22: However, testical concerns remain important because prediction without a definitive cure can create anxiety and difficult decisions.

00:10:32: Up to now we have discussed symptoms and genetics but how do doctors actually confirm the diagnosis of Alzheimer's disease today?

00:10:39: And what role does biomarkers play?

00:10:43: So Erika tell us What exactly is a biomarker?

00:10:47: Well, thank you for your question.

00:10:48: This is a really important point to be made.

00:10:51: Let's say that biomarker is the measurable biological indicator of disease.

00:10:57: In Alzheimer disease biomarkers are very important because they help identify pathological brain changes long before severe symptoms appear.

00:11:07: We're talking about ears even decades and this one of biggest revolutions in modern neurology.

00:11:14: After first clinical evaluation at MRI What happens if doctors still suspect Alzheimer's disease?

00:11:21: Well, according to Italian and Emilia Romagna guidelines.

00:11:26: If Alzheimer's Disease is strongly suspected specialists may request advanced biomarker testing.

00:11:34: I'm talking about two main approaches which are Cerebral Spinal Fluid Analysis

00:11:41: And how does Cerebro spinal fluid analysis work?

00:11:45: Well doctors like you We collect cerebrospinal fluid through a lumbar puncture, also called spinal tap.

00:11:53: And then in the laboratories they will measure levels of betamyloid total tau and phosphorylated tau proteins.

00:12:01: In Alzheimer's disease beta-myloid levels are typically reduced while tau proteins are increased.

00:12:08: And for example, in our institute these analyses are performed using advanced biochemical techniques and ultrasensitive technologies like Simoa and Clio technology.

00:12:21: What imaging techniques are used when a thymus is suspected?

00:12:26: Nowadays pet scans are extremely important but we have to make a distinction.

00:12:31: FDG PET evaluates brain metabolism, while amyloid PET can directly visualize amylloids plaques inside the brain.

00:12:39: MRI state is also routinely used to assess structural brain changes especially pocampolotrophic.

00:12:47: And Erika our blood biomarkers became part of the diagnostic process too?

00:12:51: Yes and this one of the most promising developments in current research.

00:12:57: researchers are able now detect molecules such as phosphorylated tau, neurofilament line chain and GFAP in blood samples.

00:13:06: So blood biomarkers could become excellent screening tools because they are cheaper less invasive and easier to perform than PET scans or lumbar punctures.

00:13:24: Giannicola why is early diagnosis considered so important?

00:13:29: Well um... Early diagnosis allows doctors to monitor patients more effectively and the game treatment strategies area.

00:13:37: It also gives patients and families time to plan future care, lifestyle adaptations.

00:13:44: Most importantly many experimental therapies appear to work better during early phases of disease rather than later.

00:13:52: Recently there has been a lot discussion about new treatments based on monoclonal antibodies.

00:13:59: Are these drugs available in Italy?

00:14:02: Yes they are.

00:14:04: In recent years, new immunoclonal antibodies therapies targeting beta amyloid have been developed for patients in the early stages of Alzheimer's disease.

00:14:14: The two most well-known drugs are lecanemap and donanemap but unlike traditional Alzheimer's medication which mainly helped manage symptoms these therapies aim to slow the biological progression.

00:14:32: How are these drugs administered, Giannicola?

00:14:35: Both treatments are administered through intravenous infusion in specialized centers like ours.

00:14:40: Patients also require strict monitoring because this drug can cause side effects called peria which stands for Hamilloid-related imaging abnormalities Which could be very terrible.

00:14:54: These complications may include brain swelling or small brain hemorrhages so patients need regular MRI scans to treat them.

00:15:02: And which patients can receive these therapies?

00:15:05: Well, that's a good point.

00:15:08: Current recommendations suggest that these treatments are mainly intended for patients with myocontin permit or very early Alzheimer's disease and who are confirmed of course to be amyloid-positive through biomarkers such as

00:15:22: PET scans or cerebrospinal

00:15:24: fluid analysis.

00:15:26: This means the biomarker is essential not only for diagnosis but also for deciding whether patients may benefit from these therapies.

00:15:35: So what is the situation in Italy right now?

00:15:40: Well, in Italy this situation is still evolving.

00:15:43: The Italian medicine surgeon CIFAR Is currently evaluating reimbursement criteria and organizational aspects For use of these drugs.

00:15:51: within the National Health Service Specialized neurological centers are preparing dedicated diagnostic and monitoring pathways for eligible patients.

00:16:01: Wow, it sounds good!

00:16:03: Do these drugs completely stop Alzheimer's disease?

00:16:07: No unfortunately they're not cure but let say that clinical studies suggest the monoclonal antibodies may slow cognitive decline especially in herd diseases stages But did not reverse existing brain damage.

00:16:22: However, many experts consider them an important step

00:16:25: toward

00:16:26: because for the first time treatments are targeting one of the biological mechanisms underlying Alzheimer's disease itself.

00:16:35: There also clinical trials on these more fun antibodies in Italy.

00:16:40: Andrea can you say a little bit about that?

00:16:49: Yes absolutely!

00:16:50: Italy is actively involved with international Alzheimer's research and several Ilks Institute participating in clinical trials on anti-amyloid monoclonal antibodies.

00:17:02: Also our institute is involved with research activities related to biomarkers, neurodegenerative diseases and evaluation of monoclonal antibody therapies for Alzheimer's disease.

00:17:13: Researchers from the Institute have also contributed to important scientific studies on drugs such as lecanimum and dunanimum.

00:17:23: Andrea let me just ask you one last question.

00:17:26: So clinical trials are not only testing treatments but also improving diagnosis, right?

00:17:33: Yes exactly.

00:17:34: Today clinical trials combine advanced imaging techniques blood biomarkers genetic analysis and artificial intelligence to better understand Alzheimer's disease.

00:17:45: this means that research centers such as our years are contributing but also to the creation of more accurate and personalized diagnostic pathways for future patients.

00:18:01: In conclusion, today we explored Alzheimer's disease from clinical genetic and diagnostic perspectives.

00:18:10: We also saw specialized centers such as ours in Bologna apply advanced diagnostic pathways involving neuropsychological tests imaging genetics biomarkers.

00:18:23: Also, Alzheimer's disease still has no definitive cure.

00:18:27: Research is progressing rapidly and diagnostic tools are becoming more accurate every year.

00:18:33: Early diagnosis of pneumonoclonal antibody therapies could significantly improve the management or diseases in future.

00:18:41: And with that we wrap up todays episode!

00:18:45: Thank you for joining us on this journey.

00:18:47: Stay tuned for more episodes of PHDVNM Beyond The Lab Until next

00:18:52: time.

00:18:53: Bye!