3: Demenz Flashcards
Major and Mild Neurocognitive Disorder
• Signif. cognitive decline in 1/+ cognitive domains (Complex Attention, Memory, Executive Function, Language, Perceptual-motor, Social Cognition)
• Delir / other psychiatric disorders should be excluded
Severity:
– Mild: Difficulties with instrumental activities of daily living (e.g., housework, managing money, taxes)
– Moderate: Difficulties with basic activities of daily living (e.g., eating, dressing)
– Severe: Fully dependent
Screening Instruments
• Mini Mental State Examination (MMSE)
• Montreal Cognitive Assessment (MoCA)
Neuropsychological Test Batteries for Dementia Assessment:
• CERADplus
+ Gold Standard
- Best suited for AD, less for other dementias
• CFD from Wiener Testsystem
+ Computer-based, parallel versions, RCIs
- Best suited for AD, less for other diseases
- long duration for whole assessement
• CAMDEX-DS-2
+ Dementia assessement
- no norms or cutoffs
Etiologies
• Frontotemporal Lobar Degeneration (5-10%)
• Traumatic brain injury
• Lewy Body Disease / Parkinson (10-20%)
• Vascular Impairments
• Huntington
• HIV
• Alzheimer (50-60%)
• Vascular Dementia (15-20%)
-> overlaps possible
Treatable Causes
– Hydrocephalus (too much CSF) (normal pressure hydrocephalus NPH) -> Shunt
– Spacial growth (brain tumor, chronic subdural hematoma) -> surgical removal
– Metabolic-toxic disorders (hepatic, renal, Dysthyreosis, vitamin deficiency, alcohol, substances)
– Inflammatory diseases (HIV)
– Functional cognitive disorders («Pseudodementia» / Depression)
Alzheimers
• Insidious, gradual onset over months to years, not sudden
• history of worsening of cognition
• initial, most prominent cognitive deficits in 1 of these categories: Amnestic, Language, Dysexecutive
• diagnosis of probable AD should not be applied when evidence of other variants of dementia
Clinical presentation:
– Orientation problems, esp. in unfamiliar environments
– memory disturbances (Storage) -> Word list learning very impaired
– cognitive and psychomotor slowing
– Disturbances in higher executive functioning
– Language often intact, sometimes anomia
– Apraxia (Störung der Ausführung willkürlicher zielgerichteter Bewegungen)
– Anosognosia (keine Einsicht)
– Course: subtle onset, gradual course
Down Syndrome - Alzheimers
– APP-Gen (Amyloid-precursor protein gene) is located on Chr. 21 -> triplicated
– > Very high risk to develop AD (almost 100%)
– Often very early (age of first symptoms often 40-45 years)
Assessment:
– Difficulties to report own symptoms
– Sensory and language difficulties
– Cooperation, motivation, concentration reduced
– Tasks: Floor effects (eh schon kognitiv beeinträchtigt -> braucht spezielle Tests), large variability
-> Special diagnostic instruments needed to assess dementia in DS
Vascular Neurocognitive Disorder:
• onset of cognitive deficits temporally related to 1/+ cerebrovascular events (CVE) like stroke
• decline in speed of information processing, complex attention or frontal-executive functioning in the absence of history of stroke/transient ischemic attack
- Early presence of a gait disturbance
- Early urinary frequency, urgency
- Personality and mood changes: abulia, depression, emotional incontinence
• Presence of significant neuroimaging (MRI or CT) evidence of cerebrovascular disease
- vessel infarct
- white matter lesions
- intracerebral hemorrhage
Clinical Presentation:
– Prominent cognitive and psychomotor slowing, reduced energy
– Depression
– Attention fluctuating
– Memory disturbances in recall
– Disturbances in basic and higher executive functioning
– Language intact, slowly
– No apraxia (Unfähigkeit, zielgerichtete Bewegungen sinnvoll und auszuführen)
– Insight often intact
– Course: Sudden onset, fluctuating course
– Often mixed etiology with Alzheimers Disease -> Mixed Dementia
Summary: Dementia
Alzheimers:
- subtle onset
- progressive, stable course
- Focus on memory loss
- Cortical functions impaired
Vascular Disease:
- sudden onset
- unsteady course
- Focus on slowing
- subcortical functions impaired
FLD:
- subtle onset
- progressive, unsteady course
- Focus on behavior/language
- Dysexecutive syndrome, Aphasia
Lewy-Body Dementia:
– Fluctuating cognition, pronounced variations in attention & alertness (reaction times)
– visual hallucinations, typically well formed and detailed
– REM sleep behavior disorder, which may precede cognitive decline
– 1/+ spontaneous cardinal features of parkinsonism
Clinical Presentation:
– Visuo-constructive dyspraxia
– Fluctuations and fluctuating attention
– Visual hallucinations
– No cognitive and psychomotor slowing, reduced energy
– Depression
– Memory disturbances in recall
– Possible disturbances in higher executive functioning
– Languge intact
– No apraxia
– Course: often subtle onset, fluctuating course
Dementia due to frontotemporal lobar degeneration (FTDL):
Behavioral variant:
• Early behavioral disinhibition
• Early apathy or inertia
• Early loss of sympathy or empathy
• Early perseverative, stereotyped or compulsive/ritualistic behavior
• Hyperorality and dietary changes
• Executive deficits with sparing of memory and visuospatial functions
Clinical Presentation:
– Social inappropriate behaviour
– Anosognosia
– Qualitative aspects of executive functions (perseverations, rule breaking)
– Reduced impulse control
– Impaired social cognition
– Distractable
– No prominent memory impairments
– Language intact
– No apraxia
– Course: subtle onset, gradual course
Treatment recommendations
• Acetylcholinesterase inhibitor → profit for some patients
• Neuropsychological Treatment → no standardized protocol, compensation methods
• Prism glasses
• Psychotherapy
Proteins in Neurodegenerative diseases
• Braak Stages: Tau -> AD
• Thal Stages: Beta-Amyloid -> AD
• TDP-43, FUS -> FTLD
Biomarkers in AD
Neuroimaging:
- MRI
- Amyloid PET
- Tau PET
-> to rule out vascular/structural causes
Blood:
- Beta-Amyloid
- Tau
CSF:
- Beta-Amyloid
- Tau
-> to rule out inflammatory causes
CSF Biomarkers
- 250% more Tau (neurodegeneration) in AD
- 50% weniger Beta-Amyloid in CSF
- total Beta-Amyloid secretion increases with neurodegeneration
-> 10-45 % of cognitively normal older adults are “amyloid-positive“ -> probably develope AD later
-> AD targets brain regions that are highly active in general
-> GABA and Glutamate relate to ß-amyloid and APOEε4 allele
-> More hyperactive and silent neurons, only in vicinity of Aß plaques, Likely due to loss of synaptic inhibition
ß-A: More excitation, less inhibition
Tau: less excitation
Sleep and AD
• with age sleep gets less deep/more fragmented -> with AD even more extreme
• Might be bidirectional relationship
• Sleep-wake disturbances forecast future Aß accumulation
• Excessive daytime sleepiness
- Similar NREM sleep EEG marker relate to cognitive impairment in AD and PD
Sleep and protein homeostasis:
• Sleep regulates Aß accumulation in AD mice
• Sleep restriction -> more Amyloid burden
• “glymphatic system” clears ß-amyloid during sleep
-> One sleepless night increases CSF biomarkers of AD and PD
