Demention and Alzheimer's

Dementia

Umbrella term describing a set of symptoms associated with cognitive impairment severe enough to affect social or occupational functioning. Loss of intellectual abilities, including;

• Judgement

• Orientation

• Function at work, home, community

• Attention

• Memory

• Language

• Motor and spatial skills

Alzheimer’s

Cause: Not known exactly, but believed to be due to buildup of amyloid plaques in brain, disrupting cell communication and causing neurodegenerative factors

Most common subset of dementia in people aged over 65

Vascular Dementia

Cause: Reduced blood flow to brain due to stroke, high BP, diabetes and other vascular conditions - reduces O2 supplies and causes neuronal damage

Symptoms: Cognitive impairment, motor and physical symptoms, mood and behaviour changes, etc. Can vary depending on location and severity of brain damage.

Step-wise decline. Can occur alongside other types of dementia e.g. Alzheimers - early diagnosis and treatment important for progression and improvement of QoLF.

Lewy Body Dementia (LBD)

Cause: Buildup of abnormal proteins (Lewy Bodies), specifically α-synuclein, in the brain, particularly in nerve cells

Symptoms: Fluctuation of cognitive function, visual hallucinations, problems with attention and planning, memory problems, mood changes

Lewy Bodies can also be associated with Parkinson’s disease

Frontotemporal Dementia (FTD)

Cause: Damage to frontal and temporal lobes

Symptoms: Behavioural changes, language difficulties, physical symptoms

Typically affects people between 45 and 65

Categories of Dementia

• Neurodegenerative (originally called irreversible)

• Non-neurodegenerative (potentially reversible)

Pts w dementia can and often do have multiple diseases which can be neurodegenerative (e.g. dementia w Lewy Bodies) or non-neurodegenerative (e.g. cerebrovascular disease) and contribute to impairment tgt

Most dementia in elderly pts caused by neurodegeneration

Diagnosing Dementia

Initial evaluation and diagnosis should include one of the four through GP review:

1. thorough clinical history; memory deficit test might include asking when it came on, if anything precipitated it (death of pets might cause it bc loss of communication and companionship that couldve helped slowed progression of dementia)

2. neurological exam, w an emphasis on mental status assessment - does the pt have capacity?

3. selective labs to screen for metabolic/physiological abnormalities (basic chemistries, thyroid, B12, Vit D - deficiencies can cause forgetfulness)

4. structural brain screen, MRI more than CT whenever possible bc better to look at structure as it highlights soft tissue, except in vascular dementia bc it can detect acute vascular changes. In some, serological studies e.g. antibodies, RBC, sedimentation rate, HIV-ab and heavy metal screen are warranted

Early Stage Dementia

Problems are mild and almost noticeable, often mistaken for aging.

BvFTD: Behavioural variant FTD. Commonly associated w personality changes, apathy and progressive decline in socially appropriate behaviour, judgement, self-control and empathy

PNFA: Progressive non-fluent aphasia, decline in language

Middle Stage Dementia

Changes in people are now obvious to people around them

• Daily life and relationships can be affected

• Mostly unable to do everyday tasks

• Frustration, anger, mood swings, conflicts

• Suspicion or uncooperativeness

Late Stage Dementia

Extensive damage to the brain

• Affects almost all aspects of life

• Physical changes severe

• Dependant on someone else for all activities as mobility decreases

• Ability to talk or willingness reduces

• Health worsens on multiple fronts

Seven Clinical Stages of Alzheimer’s (Global Deterioration Scale)

1. Appears cognitively normal, but pathological changes are happening in brain

2. Prodromal stage: mild memory loss, but can be mistaken for forgetfulness

3. Progression into mild cognitive impairment (MCI). Individuals may get lost or finding correct wording

4. Moderate dementia: poor short-term memory, individuals might forget some of their personal history

5. Cognition continues to decline and pt needs help in daily lives, can be confused and forget many personal details

6. Severe dementia, requires constant supervision and care. Patients cannot recognise friends, family + changes in personality

7. Individuals are nearing death - motor symptoms, communicating difficulties, incontinent, require assistance in feeding

Clock Drawing Test

Screening test

Mini-ACE (Mini-Addenbrooke’s Cognitive Examination)

Screening test socred out of 30. Cut-off scores are 25 and 21, with lower scores suggesting dementia. Questions testing memory, attention, fluency, etc.

Barriers to Dementia Diagnosis

• Misidentification of early stages as normal ages

• Social skills often maintained early in disease

• Denial by pt or family - they may feel scared

• Social stigma around diagnosis

• Lack of definitive screening and diagnostic testing

Dementia vs Alzheimer’s

Alzheimer’s Overview

• Most common cause of dementia in adult life, associated w selective damage of brain regions & neural circuits for memory cognition

• Pathogenesis is complex, involves molecular, cellular and physiological pathologies

• Neurons in neocortex, hippocampus (fear), amygdala, basal forebrain cholinergic system most affected

Amyloid Plaque Formation

• Alzheimer’s pts show plaques composed of amyloid-beta (A-beta) peptides

• A-beta peptides come from Beta Amyloid Precursor Proteins (APPs)

• APP is a glycoprotein that is normally a cell-surface signalling molecules

• APP is cleaved in the endosomal compartment of the endoplasmic reticulum or golgi complex by beta, α and γ secretases (endoproteolytic cleavage)

Presenilins

• PS1 and PS2

• Proteins with eight transmembrane domains

• Cleave APP, if mutated it can lead to the production

Neurofibrillary pathology

Abnormal changes seen in the brain that are often associated with diseases like Alzheimer's. In simple terms, it's about the build-up of tiny protein filaments (called neurofibrillary tangles) inside brain cells. These tangles can disrupt the brain's ability to communicate properly and are linked to memory problems and other cognitive issues.