Neurocognitive Assessments: Can a dementia diagnosis be definitive?

1. Neurocognitive Assessments: Can a dementia diagnosis be definitive? Lauren Bennett, PhD Post-Doctoral Fellow CCLRCBH

2. Perceptions • What do you know about neuropsychology? • Experience • Do you know someone that has had a neuropsychological evaluation? • Referred for one? • Seen a report? What’s your baseline?

3. Head shrinkers • Emotional/psychological assessment only • PhD or PsyD • Not an M.D. • Cannot generally prescribe medications* • More than a therapist • Generalist training + advanced specialized training • Most focus on assessment, diagnosis, and brief intervention • May provide psychotherapy or cognitive rehabilitation • Many worry that their evaluation results will be used to make decisions about whether they can drive, manage their own money or medications, cook, stay home alone, etc. Common Myths

4. Neuropsychology is a specialty field within the broader field of psychology • Emphasizes understanding the relationship between the brain and behavior • Conducts specialized evaluations to assess brain functioning to increase understanding about how well the brain is working • A neuropsychological evaluation involves an interview and administration of tests Brief Overview of Neuropsych

5. After an injury or illness, many people may be referred to a neuropsychologist • Although doctors are able to look at scans and images of the brain, pictures do not always show how the brain is working • The goal is to gain an in-depth understanding of current cognitive, behavioral and emotional functioning • Particularly in relation to similarly aged adults Function

6. Most people aren’t a very good judge of their own abilities • Cognition is more complex than some people realize • e.g., the “Memory Drawer” • Lots of things can influence cognition • Neurodegenerative disease • Emotional difficulties (e.g., depression, anxiety) • Some medications • Poor sleep Is this really necessary?

7. Baseline evaluation • MS • Characterizing impairment post-injury and tracking recovery • TBI, stroke • Pre-surgical evaluation • Epilepsy, DBS • Differentiating and characterizing degenerative conditions • Capacity • Medical, financial, DPOA • Neurocognitive Rehabilitation • Guiding intervention • Research • Frequently used outcome measure to test change across time When can neuropsych be helpful?

8. The tests are typically pencil and paper type tests. • Some tasks might be self-report forms (e.g., questionnaires) but most will be tests administered by a neuropsychologist or trained, skilled technician. • Some may be on a computer • Neuropsychological tests are “standardized” meaning that they are administered in the same way to everyone • An individuals scores are compared to similarly aged, healthy adults to determine strengths and weaknesses What does testing look like?

9. Premorbid IQ • Tests not sensitive to acquired brain dysfunction • Demographic estimates • Orientation • Processing speed • Simple, timed tests • Motor speed • Attention • Digit span forward • Digit vigilance How are the domains assessed?

10. Memory • Visual and verbal • Learning/encoding • Recall (immediate/delayed) • Recognition How are the domains assessed? Lemon Beer Nucleus Telephone Lemon Beer Nucleus Telephone Lemon Beer Nucleus Telephone Whiskey Lemon Television Cell ???

11. Language • Comprehension (following commands, understanding complex sentences) • Fluency (phonemic, semantic, in conversation) • Repetition • Naming (picture, auditory) • Visuospatial • Construction (blocks, drawing) • Perception • Executive • Inhibition • Set-switching • Working memory (digits backward) • Abstract reasoning (similarities, proverbs) How are the domains assessed?

12. ExamplesMental Rotation

13. ExamplesVisual Perception

14. Inhibition • RED BLUE GREEN • Abstract reasoning • Proverbs • “An old ox plows a straight row” ExamplesExecutive Functioning

15. Why its important to assess various domains? Different diseases have their own cognitive “signatures” Some parts of the brain are more vulnerable to certain diseases e.g. memory centers in Alzheimer’s disease, language centers in primary progressive aphasias Also important to assess which domains are intact If AD, simple auditory attention should be intact, at least earlier in the disease course

16. Using appropriate norms is critical • Test performance can be impacted by cultural and educational factors • e.g., MOANS vs. MOAANS • Normative information - not always enough • Example: timed visuospatial task impaired because of slow speed • Other contributing factors: • Environmental • Rapport with examiner Standardization

17. Remember that word list?

18. Bananas • Telephone • Water • Wine • Mitochondria • Lemon • Organelles • Vodka • Chromosomes • Nucleus Which ones were on the list? Beer Computer Cherries Watermelon Peaches Allele Bacteria Rum Television Microwave

19. Functional neuroanatomy: • Limbic networks responsible for episodic memory are effected first • Earliest neurofibrillary changes: hippocampi and entorhinal cortex → anterograde amnesia • Progresses to “association” cortices • Neuropsychological impairments track regional involvement Alzheimer’s disease

20. Word learning tests • Learning “ok” • “Rapid forgetting” • Can’t recall following delay • Minimal improvement with recognition cues • Retrieval deficits • Impaired consolidation (encoding) notpoor retrieval (Delis, 1991) • Increased sensitivity to interference also impacts recall and recognition(Fuld et al., 1982) • Learning affected by reduced semantic clustering (Dalla & Barba, 1995) Memory functioning in AD

21. Typical neuropsychologicalprofile in AD

22. Research shows there are cognitive and often emotional changes years before individuals meet criteria for dementia MCI & Prodromal AD: Diagnostic Confounds (Forlenza, 2010)

23. Beyond Memory: Assessment of AD as it progresses • Typically impaired: • Language • Semantic knowledge • Executive functions • Working memory • Visuospatial abilities • Relatively protected: • Digit span forward • Vocabulary • Information • Comprehension • (Similarities) Memory represent earliest changes Further decline in cognition coincides with decline in activities of daily living Neuropsychiatric symptoms common: depression, anxiety, irritability among the most frequent

24. Posterior cortical atrophy • Usually AD pathology, but can be LBD or CJD • Logopenic primary progressive aphasia • Profound word-finding difficulties and impaired phonological loop • Frontal variant • Pronounced executive and behavioral difficulties • Kluver-Bucy phenotype (Kile et al., 2009) • Hyperorality, hypersexuality, hypermetamorphosis, visual agnosia, hyperphagia, and apathy Atypical Presentations

26. Depression • “Pseudo dementia” • Delirium, NPH, etc. • Sleep deprivation • None of these have the specific deficit in retrieval seen in typical AD Excluding Mimics

27. A “subcortical” dementia • Parkinsonism + hallucinations + fluctuating cognition • Neuropsychological deficits: • Visuospatial • Executive • Attention • Memory deficit less severe than in AD, qualitatively different(Hamilton, 2004) • Learning deficit • Better recall and recognition than in AD Non-Alzheimer’s Dementia: Lewy Body Disease (Collerton, 2010)

28. Cumulative decline in cognitive functioning due to multiple infarctions, ischemic injury, or hemorrhagic lesions • Heterogeneous presentation ~ depends on distribution of disease • Usual profile includes impairments in • Processing speed • Executive functions • Construction • Sparing of • Language • Memory Non-Alzheimer’s Dementia: Vascular Dementia

29. Non-Alzheimer’s dementia: Frontotemporal dementias Behavioral variant Two language variants Nonfluent primary progressive aphasia (PPA) Semantic PPA Memory spared in early stages Can be difficult to test memory due to prominent aphasia or behavioral indifference/disinhibition

30. Alcohol-related dementia • Wernicke’s encephalopathy • Korsakoff’s syndrome • Traumatic brain injury • Depends on type of injury and severity • Epilepsy • Depends on epileptogenic foci • Can sometimes provide support for suspected brain region responsible for seizures • Attention Deficit Hyperactivity Disorder • Attention (particularly sustained attention) and executive functioning difficulties • Psychiatric disorders • Executive functioning, speed, attention sometimes affected in patients with severe mental illness such as schizophrenia and bipolar disorder (especially as they age) • Acute depression and anxiety can cause attention and executive impairments Other Disorders Evaluated in NP

31. HVLT - distinguishing early dementia from normal aging • Total recall cut-off of 18 (Frank & Byrne, 2000) • Sensitivity = 96% • Specificity: 80% • Total recall cut-off of 14.5 (Hogervost et al., 2002) • Sensitivity: 91% • Specificity: 80% How much does neuropsych add?HVLT

32. Sensitivity and Specificity • Test sensitivity is the ability of a test to correctly identify those with the disease (true positive rate) • Test specificity is the ability of the test to correctly identify those without the disease (true negative rate)

33. Sensitivity and Specificity of Memory Measures Ordered by Overall Accuracy How much does neuropsych add?VERBAL MEMORYCVLTStory MemoryMMSE (adapted from Rabin et al., 2009)

34. Sensitivity and Specificity of Verbal Memory Measures in Predicting Progressing from MCI to AD How much does neuropsych add?VERBAL MEMORYCVLTStory MemoryMMSE (adapted from Belleville et al., 2017)

35. Sensitivity and Specificity of Language Measures in Predicting Progressing from MCI to AD How much does neuropsych add?LanguageBNTCategory Fluency (adapted from Belleville et al., 2017)

36. Meta-analyses of Immediate Recall Measures for MCI vs. Healthy Controls How much does neuropsych add?Immediate Memory Measures (adapted from Weissberger et al., 2017)

37. Meta-analyses of Immediate Recall Measures for Alzheimer’s Disease vs. Healthy Controls How much does neuropsych add?Immediate Memory Measures (adapted from Weissberger et al., 2017)

38. Meta-analyses of Delayed Recall Measures for MCI vs. Healthy Controls How much does neuropsych add?Delayed Memory Measures (adapted from Weissberger et al., 2017)

39. Meta-analyses of Delayed Recall Measures for Alzheimer’s disease vs. Healthy Controls How much does neuropsych add?Delayed Memory Measures (adapted from Weissberger et al., 2017)

40. Many NP measures meet the suggested sensitivity and specificity guidelines put forth by the Consensus Workgroup (1998) for biomarkers in differentiating between patients with AD and healthy controls • Neuropsychological assessment, which is affordable, non-invasive, and widely available, can strongly contribute to an accurate MCI or AD diagnosis • Also highly effective in predicting later conversion to dementia while individuals are still in the MCI phase Take Home Points

41. Thank You!Questions?