apr 7

Contrast between poor memory and exceptional memory.
Importance of forgetting: Highlights forgetting serves important purposes, contrary to the common belief that exceptional memory is solely advantageous.

Focus on Alzheimer's disease while also touching on other related topics.
Mention of slides and additional material available for deeper exploration of memory issues.
Reminder: neurofeedback will be discussed in the last class, with potential coverage of alexithymia and preparation for the final exam.

Dementia: An outdated term that previously referred to any mental illness, meaning to be “outside of one's mind.”
Modern definitions restrict its use, as seen in the DSM (Diagnostic and Statistical Manual), which has moved towards terms like neurocognitive disorders.
Documentation of dementia-like conditions dates back to ancient Egypt, with significant discussions by notable philosophers and physicians.
Philippe Pinel: Recognized as the father of modern psychiatry; categorized mental disorders including early definitions of dementia.
Terms used historically include: - Idiocy: no longer in use. - Melancholia: with subsequent division into mania with or without delirium. - Emphasis on the change in classification of conditions, now encompassing hundreds of diagnoses. - Early notions linked dementia with mental illness as an inevitable terminal phase—this belief has since evolved.
Amo Creplin established distinction between early and late dementia.
Jean Etienne Esquirol: Introduced the concept of senile dementia related to aging, emphasizing progressive neurodegenerative conditions.

Alzheimer's Disease: Approximately 60% of all dementia cases.
Vascular Dementia: Results from repeated strokes; difficult to diagnose due to variable causes.
Dementia with Lewy Bodies: Characterized by protein clumping, pervasive throughout the brain. It can predict cognitive decline based on Lewy body count.
Parkinson's Disease Dementia: Present in 30-40% of Parkinson's cases; shows cortical Lewy bodies less significantly than Lewy body dementia.
Frontotemporal Dementia: Involves atrophy of the frontal and possibly parietal and temporal lobes; often leads to inhibitory problems and distressing behaviors.
Korsakoff Syndrome: A severe and often overlooked condition, linked to alcoholism and Vitamin B1 deficiency; profoundly impacts memory.
Other causes: HIV, Multiple Sclerosis, and Creutzfeldt-Jakob disease (prion-related illness).

History: Began with Alois Alzheimer’s research on Auguste Deterre, leading to defining markers: Amyloid Plaques and Neurofibrillary Tangles.
Early definitions of Alzheimer's related mostly to presenile forms (before age 70), but research in the 1960s greatly expanded understanding, particularly with advanced imaging methods (e.g., electron microscopy).
The DSM’s terminology changes: replaced dementia with major neurocognitive disorder in the 2013 edition, reflecting more precise definitions
Global Dementia Problem: Growing prevalence projected at 100 million people worldwide by 2050; marked gender differences in risk.
Risk Factors: Include smoking, obesity, diabetes.
Definition of Alzheimer’s Disease: A progressive neurodegenerative disorder resulting in dementia and ultimately death.

Initial Symptoms: Selective memory declines, particularly in recent and prospective memory.
Types of Memory Affected: - Prospective Memory: The ability to remember planned future actions (e.g., turning off the oven). - Episodic Memory: Decline in the ability to recall recent events more than distant ones. - Semantic Memory: Generally preserved until later stages. - Implicit Memory: Remains relatively intact even as explicit memory deteriorates.

Difficulty diagnosing Alzheimer’s without post-mortem examination of neurofibrillary tangles and amyloid plaques; living diagnosis is typically termed probable Alzheimer’s disease.
Mild Cognitive Impairment (MCI): Around 50% progress to Alzheimer's, yet diagnosis remains uncertain.
Pathological Indicators:
- Neurofibrillary tangles (tau protein) lead to synapse collapse. - Amyloid plaques (extracellular) consist of beta-amyloid and dying cells.

Clinicians must distinguish Alzheimer's from other types of dementia (e.g., vascular, Lewy bodies, frontotemporal).
Consideration of treatable causes for memory issues, such as hypothyroidism or vitamin B12 deficiency, especially in older patients with memory complaints.

Pathological markers mentioned (e.g., structural changes, amyloid, tau, synapse loss) develop significantly before clinical symptoms arise; diagnosis often happens late in the course of the disease.
The Amyloid Cascade Hypothesis posits that amyloid plaque accumulation drives the disease’s progression, but evidence from high plaque normals challenges this.
Alternative hypotheses include the Inflammation Hypothesis (excessive microglial activity around plaques causing more damage), Pathological Spread Hypothesis (similar to prion diseases).

Acetylcholinesterase inhibitors (e.g., donepezil) help moderately but mainly in early stages.
NMDA receptor antagonists (e.g., memantine) used in moderate to severe cases.
Aducanumab: A newer controversial amyloid-targeting drug aimed at clearing plaques.
Antidepressants: SSRIs sometimes prescribed for co-occurring depression but lack sufficient clinical trial support for specific use in Alzheimer's populations.
Often prescribed atypical antipsychotics to manage agitation and psychosis in Alzheimer's patients despite potential over-prescription.

Highlight of exceptional cases, the story of Luria’s patient ‘S’, a mnemonist, with eidetic memory, led to various struggles due to overwhelming memory recall and distraction.
Discussion of H.M. (Henry Molaison): Foundation in memory research, most famous case of anterograde and retrograde amnesia following bilateral medial temporal lobe excision.
Importance of lesser-known cases like MB with dramatic memory loss but little follow-up, reflecting potential biases in clinical research toward more notable cases.

Result of severe Vitamin B1 deficiency, commonly due to alcohol misuse, leading to profound memory loss.
Individuals typically require thiamine replenishment; however, many face irreversible damage due to delayed treatment.
Documentation of Korsakoff syndrome as a consequence of nutritional neglect in health circles; parallels to historical occurrences, such as in POW camps during WWII.