w3: MCI + Alzh Flashcards
Why Differentiate Between Depression and Dementia?
Importance:
Misdiagnosis can delay appropriate treatment.
Depression is often reversible; dementia generally is not.
Accurate diagnosis informs effective interventions and improves quality of life.
Overlap: Both can present with cognitive and emotional symptoms, making differentiation challenging.
Risks:
Depression increases the likelihood of developing dementia.
Older adults with untreated depression may experience accelerated cognitive decline.
Key Differences Between Depression and Dementia
Subjective Complaints:
Depression: Significant cognitive complaints, often out of proportion to objective findings.
Dementia: Less awareness of cognitive problems or minimisation of issues.
Severity of Cognitive Impairments:
Depression: Milder impairments; may stabilise or improve with treatment.
Dementia: Severe and progressively worsening deficits.
Memory Performance:
Depression: Improved recall with cues; difficulties stem from executive dysfunction.
Dementia: Poor recall even with cues; linked to hippocampal and cortical pathology.
Qualitative Patterns:
Depression: Generalised, non-specific deficits; subcortical profile (processing speed, verbal fluency).
Dementia: Domain-specific impairments; cortical profile (memory, visuospatial skills).
Effective Diagnostic Techniques
Clinical Assessment:
Focus on how each disorder contributes to emotional, behavioural, and cognitive functioning.
Educate medical team, patient, and family.
Screening for Depression:
Use psychometric instruments:
Beck Depression Inventory-II (BDI-II)
Hamilton Depression Rating Scale (HDRS)
Geriatric Depression Scale (GDS)
Neuropsychological Evaluation:
Use structured memory tasks (e.g., California Verbal Learning Test).
Repeated assessments to monitor progression:
Improvement or stability = Likely depression.
Continued decline = Suggestive of dementia.
Patterns in Cognitive Profiles
Depression:
Responds to treatment.
Effort-related deficits; struggles with delayed recall but improves with cues.
Subcortical deficits: slower processing, verbal fluency issues.
Dementia:
Structural brain changes and progressive decline.
Poor recall despite cues; recognition impaired.
Domain-specific impairments (e.g., memory in Alzheimer’s).
Considerations for Coexisting Conditions
History of depression increases the risk of persistent cognitive impairments.
Vascular disorders (e.g., stroke, hypertension) moderate the relationship between depression and dementia.
Depression can accelerate cognitive decline and the progression from Mild Cognitive Impairment (MCI) to dementia.
Differential Diagnosis Tips
Medication Review: Check for medications causing depression-like symptoms (e.g., beta-blockers, corticosteroids).
Cued Recall Tasks:
Depression: Better performance with cues.
Dementia: Limited benefit from cues.
Dual-Tasking and Praxis:
Depression: Performs better on dual-tasking.
Dementia: Struggles significantly.
Serial Position Effect:
Depression: U-shaped pattern (better recall of early and late list items).
Dementia: Recency advantage (better recall of late items only).
Key takeaways depression and dementia
Depression reflects effort-related deficits and stabilises with treatment.
Dementia reflects structural brain changes and shows progressive decline.
Late-life depression with cognitive impairment raises concerns for underlying dementia.
Screening, objective assessments, and monitoring are critical for effective differentiation.
Normal Aging: Key Facts
life expectancy, cognitive changes and practical implications
Life Expectancy:
Average: 76 years for men, 81 years for women in the US.
Fastest-growing age group: “Oldest old” (85+ years).
Cognitive Changes:
Preserved Abilities:
Implicit memory (skills/routines).
Vocabulary and general knowledge.
Declined Abilities:
Processing speed, working memory, executive control, memory (e.g., source/contextual recollection), and visuospatial abilities.
Practical Implications:
Regular neuropsychological testing is vital to distinguish normal aging from pathological decline.
Structured environments and compensatory strategies can aid cognitive functioning.
Theories of Normal Aging
dedifferentiation theory, processing-speed theory, scaffolding theory
Dedifferentiation Theory:
Decline in neural specificity; sensory and cognitive functions become more interrelated.
Implications:
Sensory impairments may cascade into broader cognitive challenges.
Neural reorganisation compensates for hippocampal and temporal lobe decline.
Processing-Speed Theory:
Cognitive decline driven by slower information processing.
Impacts:
Tasks requiring quick, complex operations.
Reduced synchronisation between cognitive stages.
Scaffolding Theory:
The brain compensates for structural decline by recruiting additional resources.
Mechanisms:
Strengthening or forming neural connections.
Involves the prefrontal cortex for compensatory processing.
Structural Brain Changes in Aging
Overview:
Volumetric shrinkage, white matter density decline, loss of dopaminergic receptors, and accumulation of neurofibrillary tangles and plaques.
Affected Brain Areas:
Hippocampus: Memory and navigation.
Prefrontal Cortex: Executive functions.
Cerebellum: Motor skills.
White Matter: Myelin degradation slows signal transmission, affecting multitasking and problem-solving.
Functional Changes:
Increased bilateral activation during tasks, compensating for structural decline.
Cognitive Changes in Normal Aging
Processing Speed:
Slower visual-motor tracking, sequencing, and set-shifting.
Earlier processed information may decay before integration.
Working Memory:
Reduced capacity to hold/manipulate temporary information.
Affects multi-step problem-solving and reasoning.
Executive Control:
Difficulty suppressing irrelevant stimuli and slower decision-making.
Memory:
Preserved: Gist retention.
Declined: Source memory and contextual recollection.
Language:
Word-finding difficulties (“tip of the tongue”).
Declined verbal fluency (semantic and lexical).
Visuospatial Abilities:
Challenges in visuoperception, visuoconstruction, and spatial orientation.
Mechanisms of Decline
normal ageing
Slowed Processing Speed:
Impacts task efficiency and accuracy.
Causes fragmented understanding due to information decay.
Reduced Inhibitory Control:
Difficulty filtering distractions, leading to attentional dysregulation.
Effortful vs. Automatic Processing:
Effortful processing declines, but automatic processing remains intact.
Practical Implications- of normal decline
Preservation of Abilities:
Use tasks reliant on gist memory or familiar stimuli.
Compensatory Strategies:
Minimise distractions; provide structured cues for effortful tasks.
Clinical Assessment:
Monitor changes regularly through neuropsychological testing to detect early pathological conditions.
Individual Factors in normal Cognitive Aging
Cognitive Reserve:
Dense neural networks and efficient synaptic connections enhance resilience.
Education and occupational complexity build cognitive reserve.
Physical Health:
Cardiovascular/metabolic health and sensory function impact cognition.
Interplay of Factors:
Education, health, and occupation interact to influence cognitive outcomes.
Dementia Definitions
Dementia is a syndrome due to disease of the brain, usually
chronic, characterized by a progressive, global deterioration in
intellect including memory, learning, orientation, language,
comprehension and judgment
Consequence: loss of independent living skills (both social and workrelated)
Mild Cognitive Impairments (MCI)
subjective and objective cognitive symptoms greater than expected
for an individual’s age and education level which do not interfere with
activities of daily life
MCI can be a transitional stage between “normal” aging and dementia
Current Clinical Diagnostic Criteria (NIA-AA, 2011)
MCI
Concern Regarding Cognitive Change:
Evident decline from prior functioning.
Concerns may come from:
The patient.
An informant (family, friend).
A clinician.
Impairment in One or More Cognitive Domains:
Cognitive performance below age/education expectations:
Memory: Difficulty learning/recalling information.
Attention: Trouble focusing or filtering distractions.
Language: Word-finding difficulties.
Executive Function: Issues with planning, decision-making.
Visuospatial Skills: Navigational challenges.
Preserved Functional Independence:
Independence in daily life maintained, with mild inefficiencies in complex tasks (e.g., paying bills).
Not Demented:
Cognitive changes do not impair social/occupational functioning significantly.
Requires evidence of intraindividual change through clinical history or repeated evaluations.
Subtypes of MCI
-
Amnesic MCI (a-MCI):
o Primary impairment in the memory domain.
o Often considered a precursor to Alzheimer’s Disease.
single domain: : impairments are evident in one memory domain
–> AD
multiple domain: impairments are evident in more than one domain (memory + other)
–> AD/VaD
-
Non-Amnesic MCI (na-MCI):
o Impairment in non-memory domains (e.g., attention, executive function, visuospatial skills).
o May be linked to other conditions such as vascular dementia or Parkinson’s Disease.
single domain: impairments are evident in one cognitive domain
multiple domain: impairmets evidenct in more than one cogntive domain
risk of = FTD, DLB, PDD
Clinical Importance MCI diagnosis
- Early Identification:
o MCI represents a critical window for intervention and monitoring, as it may progress to dementia, particularly Alzheimer’s Disease. - Assessment Challenges:
o Differentiating between normal aging, MCI, and early dementia requires careful clinical evaluation and neuropsychological testing. - Treatment Implications:
o Lifestyle modifications (e.g., diet, exercise), cognitive training, and management of comorbid conditions (e.g., hypertension, diabetes) can slow progression.
o Regular follow-ups to monitor changes in cognition and function are essential
Etiologies of MCI
causes
- degenerative: MCI as precursor to alzh- specifically a-MCI when episodic mem is impaired (learning & retaining info)
- vascular: cerebrovascular disease may incolve na-MCI- esp when executive functioning and visuospatial affected
- psychiatric: depression may have similar symptoms to MCI
- traumatic: head injury- lead to cognitive decline
other:
- medicine side effect
- metabolid factors- B12 vitamin deficiency
- neurological infections - syphilis or HIV
- chronic substance use
Prognosis MCI
Progression to Dementia:
Annual conversion rate: ~10–19% to Alzheimer’s Disease.
a-MCI: Fourfold higher risk of progression to AD.
Stability:
~41% of patients remain stable over several years.
Reversion to Normal Cognition:
~17% revert to normal cognitive functioning (often with reversible causes like metabolic issues).
factors influencing MCI prognosis
- Subtype of MCI:
o a-MCI:
Higher likelihood of progression to Alzheimer’s Disease due to its association with episodic memory deficits.
o na-MCI:
More favorable prognosis, with higher rates of stability and reversion to normal. - Underlying Etiology:
o Degenerative causes (e.g., AD): Higher risk of progression.
o Reversible causes (e.g., metabolic issues, medication side effects): Greater likelihood of improvement or resolution. - Rate of Cognitive Decline:
o Faster and more consistent longitudinal decline in cognition increases the likelihood of progression to dementia, particularly AD.
Clinical and Neuropsychological Assessment
Clinical Interview:
Gather subjective complaints from patient/informant.
Assess functional independence (ADLs and IADLs).
Screen for behavioural and emotional changes (e.g., depression, apathy).
Objective Neuropsychological Testing:
Evaluate all cognitive domains:
Memory: Episodic and working memory tasks.
Executive Functioning: Planning, inhibition.
Language: Naming, fluency.
Attention: Sustained/selective focus.
Visuospatial Skills: Navigation, perception.
Differentiation of Subtypes:
Episodic memory deficits: Likely a-MCI.
Executive/visuospatial deficits: Likely vascular-related na-MCI.
Functional Monitoring:
Observe inefficiencies in daily activities (e.g., errors in finances or driving).
Practical Implications of Assessment MCI
Recommendations for Patients:
Use memory aids and organisational tools.
Adopt healthy lifestyles (e.g., exercise, Mediterranean diet).
Stay socially and cognitively engaged (e.g., reading, puzzles).
Follow-Up:
Retest annually or as needed based on cognitive/functional changes.
Monitor progression through repeated neuropsychological evaluations.
Clinical Guidance:
Treat reversible causes (e.g., B12 deficiency, sleep apnea).
Discuss anti-dementia medications for eligible cases.
Key Neurodiagnostic Tools
PET Imaging (PIB):
Detects beta-amyloid plaques.
Elevated PIB retention indicates risk of progression to AD.
MRI:
Identifies brain volume loss and ventricular expansion.
a-MCI shows atrophy in medial/inferior temporal lobes.
APOE-ε4 Genotype:
Associated with greater risk and faster progression.
Clinical Pearls of MCI evaluation
- Significant Memory Deficits:
o Common but should be evaluated alongside other domains to identify subtype and potential etiology. - Mood and Psychological Factors:
o Assess depressive and anxious symptoms, as these may underlie or exacerbate memory complaints. - Collateral Reports:
o Ensure congruence between patient self-report and informant observations to validate findings. - Activity Monitoring:
o Functional decline in ADLs and IADLs is a strong indicator of progression. - Subtle Symptoms:
o Everyday forgetfulness (e.g., forgetting names or items) may not be clinically significant, but repetitive questioning or navigation issues are red flags.
Alzheimer’s Disease - current understanding
Alzheimer’s Disease (AD): A degenerative brain disorder characterised by progressive intellectual and behavioural deterioration.
Key Features:
Progressive memory impairment.
Prominent visuospatial and language deficits.
Preserved social skills in early stages.
Life span after diagnosis: ~10 years (can extend up to 20 years).
Impact:
Most common cause of dementia.
Global prevalence expected to double by 2030.
DSM-5 Alzheimers
DSM-5 Criteria:
Insidious onset and gradual progression of cognitive decline.
Evidence of memory and learning deficits, plus at least one other cognitive domain impairment.
No mixed etiology (e.g., absence of significant cerebrovascular or other disease).
NIA-AA Guidelines (2011):
Incorporates mild cognitive impairment (MCI) as part of the AD continuum.
Emphasises biomarkers (e.g., MRI, PET scans, cerebrospinal fluid analysis).
Recognises non-memory symptoms (e.g., language, visuospatial deficits).
Genetic testing for early-onset familial AD (e.g., APP, presenilin 1/2 mutations).
Pathology Alzheimers
plaques and tangles
hypothesis:
- plaque formation begins with abnormal misfolding of bta amyloid protein
- leads to neurofibillary tangles
- consequences: synaptic disruption and neurodegeneration.
Pathology Alzheimers
brain areas
early stanges:
- medial temporal lobe (hippocampus- episodic memory, endotherial cortex- disrupts comunication neurons and hippocampus)
mild-moderate stage:
- parietal cortex- visuospatial abilities and navigation (get lost in familiar places)
- lateral temporal love (semantic memory)
moderate-late:
- prefrontal cortex- executive functions, personality changes
- motor cortex (later)- impaired movement
late stage
- occipital lobe/ visual cortex - issues recognising faces and objects
advanced:
subcotical structures
- basal forebrain
- white matter tracs
- widespread cortical atrophy
Etiology of Alzheimer’s Disease
Primary Cause:
Accumulation of beta-amyloid plaques and neurofibrillary tangles (tau protein).
Pathological Process:
Starts 20–30 years before clinical symptoms.
Begins in the medial temporal lobes (hippocampus, entorhinal cortex).
Leads to synaptic disruption, neurodegeneration, and atrophy.
Risk Factors:
Non-Modifiable: Age, genetics (APOE-ε4 allele), family history.
Modifiable: Cardiovascular health, lifestyle factors (diet, exercise).
physiological and cognitive changes
- memory impairments
- language
- visuospatial abilities
- executive functons
- neuropsychiatric symptoms
Alzh: Memory mild stages
episodic and semantic memory first affected
alzh = progressive memory impairments
mild stages
- inconsistent but more-than-before forgetfulness
- forgetting names, phone numbers, recent conversations, misplacement of personal belongings
- missing appoitments- forgetting to remember - prospective memory
housekeeping, most activities of daily living are reasonably maintained.
clues and cues and multiple choices usually improve retrieval adn recognition.
alzh: memory moderate
moderate stage starts when imparmetns affect daily living
- forgetting becomes persistent, repetitive iterations of same statemetns.
- people cannot store info for more than a few minutes nor maintain a coherent stream of thought
- increased reliance on others
Alzh: memory severe
even most overlearned memories are lost or inaccessible, including recognition of close family or even personal idenity.
-> procedural and conditioning (implicit memory) affected last
Alzh + LTM
- lack of encoding due to hippocampal degeneration
- first explicit memory
- after implicit memory too
LTM and Alzh Assessment
Word lists: e.g. Rey Auditory Verbal Learning Test
15 common words are presented five times
After each presentation the person has to recall the words
After 20-30 minutes a delayed recall
After the delayed recall a recognition task is presented
Evaluation of:
Encoding – acquisition of information
Consolidation – storing information in long term memory
Retrieval – retrieving information from memory
normal adults: will improve with number of trials
alzh: will not significantly improve
working memory model (baddeley)
Importance of Model:
Connects cognitive decline in AD to specific brain regions and functions.
Demonstrates how working memory interacts with long-term memory, causing profound memory loss and functional impairment in AD patients.
Central Executive:
Role: Manages attention, integrates info, and coordinates tasks.
In AD: Impaired due to prefrontal cortex degeneration, leading to multitasking and decision-making difficulties.
Phonological Loop:
Role: Processes verbal and auditory info.
Articulatory Control System: Rehearses spoken info.
Phonological Store: Temporarily holds sound-based info.
In AD: Verbal memory declines (e.g., following conversations), linked to left temporal lobe damage.
Visuospatial Sketchpad:
Role: Handles visual and spatial info (e.g., mental images, spatial relationships).
In AD: Issues with navigation and face recognition, linked to parietal lobe degeneration.
Episodic Buffer:
Role: Integrates info from all components and connects to long-term memory.
In AD: Episodic memory (new/recent memories) declines due to hippocampal damage.
Long-Term Memory:
Role: Stores past experiences, knowledge, and skills.
In AD: Progressive loss of episodic and semantic memory (facts, knowledge
working memory alzh
early stages: relatively spared
moderate-severe: affected
Early Stage:
Affected: Episodic buffer, phonological loop.
Symptoms: Memory lapses, verbal communication issues.
Moderate Stage:
Affected: Visuospatial sketchpad, central executive.
Symptoms: Disorientation, inability to coordinate tasks.
Advanced Stage:
Affected: All components.
Symptoms: Severe memory loss, functional decline.
Working Memory Assessment Using Digit Span Test
Purpose: Measures working memory capacity, focusing on short-term retention and manipulation of information.
Tasks:
Digit Span Forward: Tests simple attention and the ability to repeat numbers in the same order they were presented.
Digit Span Backward: Evaluates working memory and executive functioning by requiring numbers to be repeated in reverse order.
Alzh and visuaspatial and perceptual functions
associated with pathology in visual association cortex.
occurs early but not clinically apparent until memory and attentional disturbances are fully established.
Difficulty navigating familiar places, dressing (apraxia), recognising objects/faces.
assessment: copy complex figure rey
clock drawring
Alzh + Language
aphasia
aphasia: aquired language disturbance
early: word finding difficulty, speech less spontaneous, speech becomes empty.
moderate: auditory comprehension deteriorated, anomic confrontations.
- basic language structure intact
severe: ppl become dysprosodic (atypical/ absent rhythm)
some develop reiterative speech (echolia: repeating others words, palilalia: releating their own words)
finally become mute
Apraxia in Alzh
: a family of cognitive motor disorders that entail the loss or
impairment of the ability to program motor systems to perform
purposeful skilled movements
ideational: failure to minic or perform gersture and demostrate the sequence of actions without using actual object.
ideomotor: inability to do on command or imitate an act that can be performed automatically. ie. brushing teeth
assessment: by giving comands
‘pretent to comb your gair’
‘pretent to bush your teeth’
-> rarely an early disabeling symptom
Alzh: Attention & Executive functions
attention is preserved in early stages
people eventually become distractable
executive functions are impaired in mild stages–> often lead to imparied dailty functioning
Alzh+ neuropsychiatric issues
core feature of alzh
occur early for some
once established, some evolve, some stay stable
Behavioral deterioration may be triggered suddenly by an acute
stressor, e.g. a change in environment
Changes range from apathy and social withdrawal to disinhibition,
agitation, eating disorders and psychosis
Alzh personality and social behaviour
Early stages
Personality and social behavior are broadly preserved
Subtle indifference or emotional detachment may be present
Many people with Alzheimer’s disease function well socially
Consequence: others underestimate or excuse cognitive impairments
alzh + Apathy (most common)
Definition
Lack of motivation relative to the person’s baseline state
Ranges from mild passivity and loss of interest to abulic immobilization
Can be misdiagnosed as depression
Strongly associated with anosognosia (deficit of self-awareness) and
executive dysfunctions
People with apathy and Alzheimer’s disease are more dependent with
regard to their activities of daily living than people with Alzheimer’s
disease without apathy
other neuropsych issues alzh
Delusions and hallucinations
Delusions are more common than hallucinations and usually are persecutory, involving
fears of personal harm, property theft and spousal infidelity
Hallucinations are usually visual
Predict more rapid functional and cognitive decline
Depression
Alzheimer’s disease and depression often coexist and symptoms overlap
Depression often precedes the development of Alzheimer’s disease
Aggression and agitation
Provoked by:
Confusion due to cognitive, memory, or language impairments
Delusions
Depression in a person too impaired to express distress in another manner
Sleep disturbance
alzh- summary
Core feature: impairments in memory
Learning new information
Other cognitive impairments in:
Language
Visuospatial and perceptual functions
Praxis
Attention and executive functions
Neuropsychiatric disturbances are often present
Most common: apathy
