Lecture 7: Alzheimer’s Disease 2 Flashcards
Alzheimer’s disease
Executive Functions (EF)
- Impairments of EF common in AD
- already in early stage
- impaired relative to HC on set shifting, flexibility (e.g. WCST), planning (e.g. ToL), inhibition (e.g. Stroop)
Executive functions
- Stroop in AD (Bondi et al., 2002)
Stroop in AD (Bondi et al., 2002)
- 51 healthy controls, 59 probable AD
- AD - more errors word reading, color reading, color-word reading trials
- AD - interference score impaired (CW/C)
- No difference mild, moderate AD subgroups (Dementia Rating Scale)
- mild AD already degree psychomotor slowing and inhibitory deficit
Executive Functions in Alzheimer Disease: A Systematic Review (Guarino et al., 2019).
- Stroop – most consistently impaired
- Accuracy
- RTs
- Interference
AD very mild (MMSE 26) – moderate (MMSE 16)
- WCST – deficits inconsistent
- problem with task difficulty
- floor effect
- Flanker – no consistent group differences
- Go-NoGo – majority studies no difference
AD: MMSE 18 - 25
Language Impairments (AD) early vs later stage:
- Most language related capabilities intact in early stage but impaired in later stage
Visuospatial abilities in AD:
Visual Search (Foster et al., 1999):
Mental Rotation (Lineweaver et al., 2005):
- Impairments typically mild in early stage
- severe impairments as disease progresses
- loss of orientation – lost in familiar surroundings, even their own home
- Visual search: feature (single feature) vs conjunction (two features) search:
- AD slower than HC, even in feature search
- impairment more severe in more advanced AD
- Mental rotation
- AD slower to respond (mentally rotate)
- Accuracy lower in AD patients, greater decline with increasing angles
Visuospatial abilities in AD:
Clock drawing (Rouleau et al., 1992):
Clock drawing
- Draw clock from memory, copy clock
- Errors AD mainly conceptual errors, e.g.
- drawing clock without numbers or without hands
- setting time (10 past 11) incorrectly (Rouleau et al., 1992)
- Clock drawing errors in AD
- Conceptual errors - deficit accessing knowledge
- danger with using it for screening is that often healthy elderly have difficulties with this task (but much larger in AD)
Visuospatial abilities
¨Posterior cortical atrophy (PCA) – associated with AD:
Posterior cortical atrophy (PCA) – associated with AD
- Predominantly AD pathology in posterior cortical regions: posterior parietal, occipital
- visual variant AD
- visual functions impaired, e.g. reading, object recognition (visual agnosia)
- relatively preserved memory and language
- Prevalence PCA unknown – 5% in sample 523 AD patients
- Onset PCA earlier than typical amnestic AD, in 50s or 60s
Neuropsychological change
Typical pattern memory and EF impairments in early stage AD:
(Weintraub et al., 2012)
Typical pattern memory and EF impairments in early stage AD
- with progression more functions affected
- pattern impairments less distinct from other forms dementia
- early stage dementia seems to impact memory the most compared to other functions like behavioural ones
(Picture: the larger the black bar the more severe the impairment)
Severity and profile of cognitive impairments varies with age at diagnosis. AD.
(Salmon & Bondi, 2009)
- Severity and profile of cognitive impairments varies with age at diagnosis.
- someone diagnosed below 70 mostly impaired in memory and EF, those above 80 all functions are imapaired to a similiar degree
- patients are compared relative to healthy individuals of the same age
- Different form AD?
Sex differences in AD:
Cognitive impairments.
Sex differences in AD:
- AD more prevalent in women
- Cognitive impairments more severe in women with AD
- Laws et al. (2018) review 298 articles:
- Women with AD < men with AD
- episodic memory, semantic memory, verbal abilities, visual spatial functions
- Effect sizes small (d= 0.2)
Sex differences in AD
- AD more prevalent in women, possible causes:
Genetic – APOE4 (Mielke et al., 2014)
- Single APOE 4 allele: women 4X higher risk AD, men little increased risk
- Autopsy study: plaques and tangles most prevalent in female APOE 4 carriers
Hormones – changes in oestrogen levels
- Hormonal replacement therapy (HRT) in mid life can reduce risk AD ( although evidence not consistent)
- HRT after menopause can increase risk AD
Cognitive reserve
- Persons with more CR greater capacity to cope with brain pathology
- Education and occupation important factors CR
Early cognitive predictors AD
- Episodic memory disturbances years before diagnosis:
- Delayed recall CVLT performance in healthy older adults predictor of subsequent progression to AD (Bondi et al, 1999)
- Memory performance poorer in persons converting to AD 3 years later
- learning score CVLT ( California Verbal Learning Test) distinguished normal group (controls), MCI (questionable) and converters (MCI converted to probable AD (Albert et al., 2001)
- poorer episodic memory than persons who remained cognitively healthy 6 years before diagnosis (Bäckman et al., 2001)
Early cognitive predictors AD
- Mild impairments episodic memory as early predictor AD
Mild impairments episodic memory as early predictor AD
- aMCI more likely to convert to AD than naMCI
- aMCI referred to as “MCI due to AD” (memory impairment + biomarkers)
How do memory impairments compare with preclinical biomarkers for AD? (Jedynak et al., 2012)
Hypothetical model of changes in biomarkers for AD (Jack et al., 2010)
(Jedynak et al., 2012)
- Used (Jack et al., 2010) Model but added memory
- Delayed free recall Rey Auditory Verbal Learning Test (RAVLT30): earliest predictor AD. Preceded hippocampal volume, amyloid beta and tau.
Early cognitive predictors AD
- Stable memory impairments may worsen shortly before symptoms AD:
- Lange et al. (2002)
Stable memory impairments may worsen shortly before symptoms AD
Lange et al. (2002):
- participants completed at least two annual evaluations.
- NC participants classified as nondemented at both evaluations.
- AD diagnosed with possible or probable AD at both evaluations.
- Preclinical AD diagnosed with possible/probable AD at last evaluation AND normal/MCI in preceding evaluation
Performance preclinical AD group on CVLT at 2, 1 and 0 years before diagnosis. Little difference APOE 4 positive or negative (Lange et al., 2002).
- it seems like decline is most steep in those shortly before being diagnosed.
- Little difference APOE 4 positive or negative (Lange et al., 2002).
Early cognitive predictors AD.
Episodic memory
EF
Semantic Knowledge
(Mickes et al , 2007)
- Converters: older adults who were cognitively normal 1 and 2 years prior to diagnosis probable AD (in year n)
- Sharp drop memory years before diagnosis.
Early cognitive predictors AD
- Decline in episodic memory related to progress of neuropathology?
Rapid decline shortly before clinical stage:
- point where compensation increasing neuropathology no longer possible
Associated clinical features of AD
- Prevalence behavioural disturbances (Lyketsos et al., 2002)
- N = 258 persons diagnosed with AD
- Neuropsychiatric Inventory (NPI) completed by informant
- Review and meta-analysis (Zhao et al., 2016)
- 48 studies
- > 10.000 persons with AD
- 12 NPS of NPI
- Most common: apathy, agitation, depression, sleep disturbances and irritability
- 50% persons with MCI behavioural disturbances over the course of condition
- Graph: (Zhao et al., 2016)
- apathy, depression, aggression most common
- Prevalence apathy – affected by education level and severity cognitive impairments
- Prevalence depression - affected by age
- Prevalence aggression - affected by age and duration of disease
- Least common euphoria
- Wide variety in prevalence
- apathy, depression, aggression most common
