Dementia: The Role of Neuropsychology and Finding the Right Diagnosis

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1 Dementia: The Role of Neuropsychology and Finding the Right Diagnosis Robert E. Cohen, PsyD Director - Department of Neuropsychology Orlando Health Memory Disorder Clinic

2 OBJECTIVES: Discuss the role of the Neuropsychologist and the Neuropsychological Assessment Articulate the importance of establishing an early clinical diagnosis, and the need for tracking change over time. Discuss the definition of normal age related decline, MCI, and dementia Describe the prevalence and believed mechanisms of Alzheimer s disease (AD), behavioral and cognitive symptoms, and approved treatments (both pharmacotherapy and behavioral) for AD. Discuss the importance of ruling out other forms of dementia/other potentially reversible causes and their prevalence. Discuss the impact of clinical depression/anxiety in dementia. Report on current pharmaceutical treatments of dementia

3 The Neuropsychologist Neuropsychology is the study of the brain-behavior relationship. A Neuropsychologist is a licensed doctor of Clinical Psychology (Ph.D. or Psy.D.) who has completed an average of 6-7 years of graduate school (post college) with specialty training (internship and residency) and/or board certification in neuropsychology and functional neuroanatomy.

4 What is a Neuropsychological Assessment? Neuropsychological assessment is a standardized and objective question/answer type evaluation that identifies how various parts of the brain are functioning and how different types of damage or disease processes ultimately affects a person s behavior and emotional processes. Mapping out the function of different parts of the brain. Intellect, memory, language, visual-spatial, executive fxn. Average length of face to face assessment is 2-6 hours depending on the referral question. Scores are adjusted for age, education, gender, and race Picture from:

5 What is a Neuropsychological Assessment? A thorough clinical interview with a family member or trusted friend who knows the patient well (can discuss ADL functions) Especially needed in cases of brain injury or dementia to assess for premorbid (previous) function. Tests are administered by the doctor or trained psychometrician. The clinical interview, results and diagnostic impressions are always performed by the doctor. This helps establish a baseline

6 What do Test Results Indicate? Individual cognitive and psychological strengths and weaknesses are determined. A neuropsychological assessment may help to determine the type and level of dementia impairment. Localization of brain impairment is discussed The results of all medical tests (Cognitive scores, MRI, CT, MRA and blood work etc.) are integrated into the diagnostic impressions and into a formal report with specific recommendations. Helps to guide future treatment goals and plans. Helps to educate family members about their loved one.

7 Benefits of Early Detection 1) Early identification and appropriate referral by the PCP can reduce the number of patient visits. 2) Dementia may go unnoticed especially very early on. **Patients may present with Anosagnosia (poor insight) **Spouses may compensate and/or cover for the patient s deficits 3) Early diagnosis could delay progression of the illness for up to five years if provided with early treatment. 1 4) New medications may have their greatest efficacy in slowing the progression of the illness early on. 5) Allows the patient to have a greater role in planning for their future.

8 Benefits of Early Detection 7) Misdiagnosis and treatment can lead to increased anxiety/depression. 8) Limited insurance qualification 9) Avoids unnecessary medication 10) Screening Tests by the PCP may be able to identify people with undiagnosed dementia. Mental status tests in the office (PCP/neurologist) may be insufficient or insensitive in identifying very early stages of a neurological disease or differentiating different types of the disease.

9 Common Presenting Problems Which one could be dementia? Pt s wife says there have been changes in her husband s driving. He is more reckless and is getting lost more frequently. Spouse notices his wife is not taking her meds on schedule and bills are not being paid on time/double paid. Family reports that Mom has become more paranoid lately but her memory appears fine. You notice your patient seems to have memory problems but also seems more depressed and anxious Your patient has decreased memory and also a history of heavy substance abuse and uncontrolled diabetes. Dad has become confused and disoriented and is repeating himself frequently while in the hospital. Does he have Alzheimer s Disease?

10 Assessing Brain Functioning and Localization of Impairment Picture from: The Simpson's, Matt Groeing (1999)

11 What is Normal Age-Related Decline? Declines in cognitive abilities is a normal process of ageing. Age-Consistent Memory Decline indicates intermittent or very mild memory changes NOT greater than expected for age/education and which is not impacting activities of daily living. Based on neuropsychological test results.

12 What is Normal Age-Related Decline? Forgetting where you put your keys, misplacing objects Why you came into a room The name of someone you know or just met Hard time thinking of a word Occasionally forgetting how to get somewhere you have been to before **Less concerning for a degenerative problem if: 1) you recognize the error or the event after being reminded, 2) the word or memory comes to you later after being reminded, 3) this only happens a few times a day and does not interfere with your life.

13 Mild Cognitive Impairment (MCI) Ronald Peterson, M.D. has described MCI as a transitional state where an individual is not cognitively normal compared to previous abilities but does not meet criteria for dementia. Pt. usually expresses or is aware of cognitive complaints Amnestic subtype (memory is the complaint or symptom) vs. non amnestic subtypes (memory not biggest complaint) Progression from MCI Amnestic subtype to AD occurs more frequently than normal elderly. Up to 15% a year/40% in three to six years with a diagnosis of Mild Cognitive Impairment.

14 Criteria for Dementia (DSM IV-TR) Dementia is a clinical diagnosis based on symptoms *Memory impairment & at least 1 or more of the following cognitive disturbances: A) Aphasia (language disturbance) B) Agnosia (failure to recognize or identify objects) C) Apraxia (inability to perform skilled movements) D) Executive dyscontrol (difficulty, planning, organizing, sequencing, abstracting etc.) E) Symptoms must cause significant impairment in social/occupational functioning and represent a decline from premorbid (previous functioning). F) May not occur during an episode of delirium * Differs from ICD-9/10 definition which does not necessitate memory impairment to meet criteria

15 3 Major Types of Dementia (*in order of prevalence) 1st - Alzheimer s disease (cortical) dementia (70%) 1 2 nd - Lewy Body dementia (23%) (66% also with AD) 1 - Parkinsons 3 rd - Vascular dementia (18%) (77% also with AD) 1 The cause of dementia is many times heterogeneous (of mixed cause). 1 MDC Brain Bank collaborative study, 2002

16 Delirium vs. Dementia DELIRIUM An acute confusional state caused by some medical condition Unable or difficult to maintain attention/concentration during testing Fluctuating, clouded consciousness Fast onset, potentially reversible Causes: NPH, UTI, Medication Effects etc. DEMENTIA Attention is typically unaffected Consciousness stable Usually slow (except with an acute vascular event), progressive and irreversible **Delirium is often misdiagnosed as dementia in up to 60% in nursing homes/ and 40% in elderly patients in hospitals)

17 Alzheimer s Disease (AD) Alois Alzheimer, MD ( ) In 1906 he described an 'unusual disease of the cerebral cortex' which affected a woman in her 50 s, causing memory loss, disorientation, hallucinations and ultimately her death at age 55. An autopsy of her brain described dense deposits around the nerve cells (neuritic plaques). Inside the nerve cells were twisted bands of fibers (neurofibrillary tangles).

18 The Impact of AD Most common form of dementia (70%) There were an estimated 4.5 million individuals with AD in the year 2000 Expected to rise to as high as 13.5 million by the year Third most expensive disease to treat next to cardiovascular disease and cancer. There are two high costs involved: 1) the cost to the patient in direct care (estimated 29.2 billion annually in 1998) and 2) the cost of loss of caregiver productivity (47,000 per patient caregiver annually 1).

19 Alzheimer s Clinical Course and Behavioral Presentation Common behavioral/cognitive presentation MCI (amnestic) to Mild Dementia: faltering recent memory, navigational disturbance, naming & speech (language disturbance), remote memory usually intact (temporal lobe is affected). Insight good to fair. Moderate: more rapid short term memory loss, frontal lobe signs, disorders of visuospatial orientation, calculation, comprehension, judgment, Insight becomes poor, may display significant emotional lability. Severe: More rapid decline of memory, usually disoriented to time and place, more behavioral or mood issues present, may present with poor hygiene and grooming ability, few ADL s intact, cannot make decisions, needs assistance. Profound: loss of motor skill (due to disease affecting the motor cortex and cerebellum) & sphincter control, may be bed ridden, unable to communicate needs effectively.

20 Mechanisms of Alzheimer s Disease The disease process usually starts in the mesial temporal area of the brain spreading eventually to the rest of the cerebral cortex (prefrontal/parietal/occipital), relatively sparing the motor strip until late stage. AMYLOID PLAQUES One of the hallmarks of Alzheimer's disease is the accumulation of amyloid plaques between nerve cells (neurons) in the brain. Amyloid is a general term for protein fragments that the body produces normally. Beta-amyloid is a fragment of a protein that is snipped from another protein called amyloid precursor protein (APP). In a healthy brain, these protein fragments would be broken down and eliminated. In Alzheimer's disease, the fragments accumulate to form hard, insoluble plaques.

21 NEUROFIBRILLARY TANGLES Neurofibrillary tangles consist of insoluble twisted fibers that are found inside of the brain's cells. Consist of a protein called tau which forms a microtubule Helps to transport nutrients in cell In Alzheimer's disease, however, the tau protein hardens and the microtubule structures collapse.

22 Alzheimer s Disease and Anatomy MRI

23 PET Scan in Alzheimer s Positron emission tomography (PET) scanning- measures brain glucose metabolism temporoparietal activity is the most common pattern may discriminate mild/moderate AD cases from normal controls (Silverman JAMA 2001; 286:2120 7) Can show change in brain function but does not specify as to WHAT is causing the change in metabolism

24

25 Case Presentation 1 68 y/o woman who s family complains of relatively progressive but vacillating changes in memory and alertness, visual hallucinations (non-bizarre), and the onset of movement difficulties and tremor upon initiation. She reports seeing fire hydrants as little children and pictures on the wall as birds or faces. There are no delusions (strange beliefs) associated with what is seen and she does not seem very bothered by her hallucinations.

26 Lewy Body Disease (LBD) 2nd most common cause of dementia (23%) (66% also with AD) 1 - Parkinson's disease Marked by diffuse Lewy bodies in cerebral cortex/brainstem Similar pathology to Parkinson s Dementia

27 Clinical Diagnosis of LBD Progressive cognitive decline and 2 or more of the following fluctuating cognition, attention, alertness recurrent visual hallucinations (Lewy bodies in the occipital cortex) motor features of parkinsonism Features supporting the diagnosis recurrent falls, syncope, neuroleptic hypersensitivity, other hallucinations

28 Case Presentation 2 72 yo male with history of atrial fibrillation, high cholesterol, hypertension, and chronic alcoholism is evaluated for dementia. His son gives history of stepwise decline (non-steady) over past 5 years with the accumulation of mild focal neurologic deficits (physical changes in his ability to perform skilled movement).

29 Vascular Dementias-Multi-Infarct Dementia 3 rd most common type of dementia (18%) (77% also with AD) 1 Multiple large vessel strokes-which may: have focal neurological signs present with stepwise deterioration (due to small recurrent strokes/events), with partial improvement or plateau. Single stroke in the middle of the brain, or one at the hippocampus etc. Post-anoxic encephalopathy (lack of oxygen to the brain)

30 Relationship Between Vascular Dementia (VD) and Alzheimer s (AD) Pure AD or VD dementia is rare High cholesterol and ischemia in the increases - amyloid production in the brain. Nun Study- subjects whose brains harbored vascular lesions showed dementia, whereas those without vascular lesions but with equivalent amounts of Alzheimer pathology were not. Snowdon DA. JAMA 1997;277:

31 Vascular Dementias-Small Vessel Disease

32 Less Common Causes of Dementia Infectious Syphilis Creutzfeldt-Jakob HIV (AIDS) Neurologic: Progressive Supranuclear Palsy Normal Pressure Hydrocephalus Picks Disease Huntington s chorea CNS mass lesions Nutritional/Metabolic Wernicke s, B12, thiamine, niacin, hypothyroidism, Wilson s, Korsakoff s

33 Case Presentation 3 72 yo man is evaluated in the office because of progressive urinary incontinence and occasional falls for one year. His family has noticed that his concentration, speed of thought, and memory have become gradually impaired over the past 6 months. Physical Exam: Wide-based stance with short steps. He scores 25/30 on MMSE. No tremor or rigidity in the limbs, but mild generalized bradykinesia is present.

34 Neurological/Normal Pressure Hydrocephalus Presents with classic triad of : 1) dementia, 2) gait disturbance (wide based magnetic), 3) urinary incontinence 50% idiopathic(unknown cause) 50 % associated with: meningitis, trauma, radiation-induced, subarachnoid hemorrhage, blockage of CSF Can be treated with drainage of Cerebrospinal Fluid - initial improvement with serial lumbar puncture. 50% pts improve with Ventriculoperitoneal shunting

35 Normal Pressure Hydrocephalus

36 Always rule out depression!

37 Depression and the Elderly In older citizens who live in the community, the rate of clinical depression has been reported as high as 13%. As many as 20% to 25% of older patients with concurrent medical illnesses are depressed. Depression often accompanies or precedes progressive dementia (AD or VD approximately +/- 25% of all cases. The rate of suicide is highest among older adults compared to any other age group and the suicide rate for persons 85 years and older is the highest of all twice the overall national rate. This is especially true for men.

38 Depression and Dementia Memory and learning functions are impaired in depressed patients. Retrieval deficits are apparent in depressed patients. May be due to poor initial processing. However, "effort for recall may also be a factor because a person s ability to recognize is less impaired than their ability to spontaneously recall information.

39 Depression and Dementia When associated with dementia there may not be a history of depression in the past. Depression is present in a very high number of early dementia cases. Often accompanies/precedes progressive dementia ~ 25%. Essential features of an depression associated with dementia 1) apathy 2) increased irritability 3) diminished ability to think, concentrate, remember, or initiate.

40 The Onset of Depression and Dementia May be related to changes in the structure and/or functioning of the amygdaloid body during AD which is rostral to the hippocampus (amygdalate in purple)

41 Pseudodementia Refers to dementia caused/maintained exclusively by a depressive state. Pt demonstrates decreased motivation during the exam. Very poor self-esteem, gives up very easily Expresses severe cognitive complaints Intact language skills (unlike typical dementia) May perform better on harder cognitive tasks due to need for increased internal motivation Improves with antidepressant treatment and individual therapy. No impairment with clock drawing test Bodner T, et al. JAGS 2004;52:

42 TREATING DEMENTIA

43 Therapeutic Approach to the Patient with Dementia Treat any reversible causes Managing associated behaviors & affective disorders with neurology and psychiatry Minimize any anticholinergic or CNS active medications Maximizing the patient functional skills Address legal & financial issues at the time of diagnosis Monitor the needs of the caregiver and refer Maximize social interactions* *Arch Intern Med 1999;131:

44 Common Memory Medications ARICEPT - (Donepezil) - Acetylcholinesterase Inhibitor approved for use with AD (approved for all stages of dementia) EXELON (Pill/Patch) Rivastigmine - Acetylcholinesterase/ Butylcholinesterase Inhibitor (approved for use with mild to moderate AD and mild to moderate Parkinson s related dementia and behavioral related changes) RAZEDYNE/REMINYL (Galantamine) Acetylcholinesterase inhibitor indicated for mild to moderate AD and Vascular Dementia NAMENDA (Memantine) works by blocking NMDA glutamate receptors - indicated for use with moderate to severe dementia - approved for use in AD - May be used as monotherapy or adjunctively AXONA A Medical Food addresses the decline in glucose metabolism a wellcharacterized feature of Alzheimer s disease by delivering an alternative energy source. It is converted into ketone bodies (medium chain triglycerides) and does not increase cholesterol.

45 Clinical Trials Compass Research exploring the role of removing amyloid plaque from the brain through lumbar puncture. New drug trials Dr. Craig Curtis, M.D. 100 W. Gore St., Orlando, FL (407)

46 To schedule a neuropsychological assessment : Orlando Health Neuropsychology Department 32 W. Gore St. 5 th Floor Orlando, FL ph / fax Need referral from your physician Need previous medical records faxed prior to appointment Accept most forms of insurance including Medicare Can see Spanish-speaking patients starting in October 2010 Plan to be at the evaluation most of the day.

47 From his neck down a man is worth a couple of dollars a day, from his neck up he is worth anything that his brain can produce. Thomas Edison

48 THANK YOU Additional References 1. American Psychiatric Association. (2003). Diagnostic and statistical manual of mental disorders (fourth text revised). Washington, D.C.: Author. 2. Kaszniak, A. W. (1986). The neuropsychology of dementia. In I. Grant and K. M. Adams (Eds.), Neuropsychological assessment of neuropsychiatric disorders (pp ). NY: Oxford University Press. 3. Caine, E. D. (1986). The neuropsychology of depression: The pseudodementia syndrome. In I. Grant and K. M. Adams (Eds.) Neuropsychological assessment of neuropsychiatric disorders (pp ). NY: Oxford Press. 4. MacInnes, W. D., & Robbins, E. E. (1987). Brief neuropsychological assessment of memory. In L. C. Hartlage, M. J. Asken, & J. L. Hornsby (-Eds.). Essentials of neuropsychological assessment (pp ). NY: Sprinqer Publishing Company. 5. Lezak, M. (1985). Neuropsychological assessment. N.Y: Oxford University Press. 6. Jenike, M. (1988). Depression and other Psychiatric disorders. In M. S. Albert and M. B. Moss (Eds.), Geriatric neuropsychology (pp ). NY: The Guilford Press.

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