9/6/2014 Who is this?€¦ · 15/9/2014 · -Predominantly aerobic (i.e. walking) interventions...
Transcript of 9/6/2014 Who is this?€¦ · 15/9/2014 · -Predominantly aerobic (i.e. walking) interventions...
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Dementia Assessment: Delaying Progression
September 15, 2014
BJ Messinger-Rapport, MD
Cleveland Clinic
Who is this?
Agatha ChristieQueen of Crime!
B: 1890
England D: 1976
Age 85
1st novel:
Mysterious Affair at Styles(Poirot)
Last novel she wrote:
1973 Postern of Fate
1934 Murder on the
Orient Express Her 80’s
Alzheimer Disease
1955 Mystery Writers of AmericaGrand Master Award
Dame Commander of the British Empire
1926 Murder of
Roger Ackroyd
Murder on the Orient ExpressAgatha Christie Age 44
83 years oldPostern of Fate
What do you see in 1973 compared with 1934?
• Creative
• Desire to contribute
• Rambling
• Paucity of words
• Simpler ideas
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What Is Dementia?
• Dementia is a general term for a decline
in cognition
- severe enough to interfere with
activities of daily living.
• Dementia is not a specific disease. It's an overall term that describes a wide range of symptoms
Cognition?
• Memory – short term, long term, working memory
• Communication and language
• Ability to focus and pay attention
• Reasoning and judgment
• Visual perception
• Problem solving, Executive function
Activities of Daily Living?
Basic (BADL)
• Eating
• Bathing, grooming
• Toileting
• Dressing
- Choosing clothes
- Putting on in order
• Transfer
• Locomotion
Instrumental (IADL)
• Transportation
- Driving, other means
- Keeping appointments
• Shopping
• Homemaking
- Cooking, cleaning
- Washer, drier
• Mail, money, medications
• Telephone & other technology
• Caregiving, pet care
Stages of dementia
• Mild
- Intact Basic ADL; impaired ≥ 1 IADL*
• Common: meds, appointments
• Moderate:
- Impaired in ≥ 1 IADL + ≥ 1 BADL
• Common: grooming
• Severe:
- Impaired in most IADL, BADL
BADL are the “basic” ADL; IADL are the “complex” ADL
Impact of MILD dementia
• Moderate memory, mild functional deficits
• Doctors, family may miss the diagnosis
• Needs assistance or oversight in
- Medication management
- Appointments
- Finances, Big decisions
• MAY continue to drive
- If allows periodic safety evaluation
Conversation in mild AD
• Current events
- Socially appropriate
- Vague- lots bad things, war
- Trouble naming recent presidents
• 10 years ago- the 911 incident
- “Bombing”, many killed. Date/year?
- May not recall plane -> Pentagon.
- May recall plane down in PA.
• Pearl Harbor
- Date? Combatants? Which war? Ships?
- Likely to remember it all!
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Impact of MODERATE dementia
• Moderate to severe memory loss
• Moderate functional deficits
• Can “pass” at a party
• Requires daily prompting or assistance
- Grooming; Bathing (prompting)
- Dressing (choosing clothes)
- Meal prep (disconnected stove)
• No driving
Impact of SEVERE dementia
• Only fragments of memory remain
• Severe functional deficits
• Cannot “pass” for normal even briefly
• 24 x 7 care
- Where? Depends upon
• Finances, Personality
• Family emotional, physical resources
Does a person go from “normal aging” to “dementia”
overnight?• If stroke, traumatic brain injury,
- Can be overnight!
- Ex: Classic vascular dementia
• If Alzheimer’s disease
- Progressive, gradual
- 20 years….
• If mixed (vascular, Alzheimer disease)
- Progressive but bumpy
Dementia types
• Alzheimer's disease
• Vascular Dementia
• Mixed
• Post-infectious (meningitis)
• Parkinson’s disease or parkinsonism
• Trauma
• Often only distinguishable early in the disease
Genetics & Alzheimer’s Disease
• Early onset dementia- destined
APP, PS1, PS2
• Late onset dementia- influence only
ApoE e4
- Onset, intensity influenced by
• Lifestyle, comorbidities
Typical occurrence of manifestations
of Alzheimer's disease.
Sloane, AAFP, 1998
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Mild Cognitive Impairment
U of California Irvine ADRC
Who is likely to progress from MCI to Dementia?
• Small hippocampal volumes
- MRI
• Decreased blood flow to posterior cingulate gyrus
- PET, amyloid scans
• Certain CSF markers
- High tau protein, Low beta amyloid (1-24)
NONE COLLECTED TYPICALLY DURING ROUTINE CARE
Risk Factors for worsening cognitive impairment
Fixed
• Male
• Advanced age
• Lower Education
• APOEe4 genotype
• Smoking, alcohol
• Lifestyle
- Socialization
- Cognitive stimulation
- Physical exercise
• Diet
• Certain drugs
• Vascular disease
• Medical conditions
Potentially Modifiable
Medical conditions associated with impaired cognition
• Sleep apnea
• Atrial fibrillation
• Heart Failure
• Diabetes
• Stroke
• Hypertension
Pharmacological Interventions
Mild Cognitive
Impairment
Mild Dementia
ModerateDementia
SevereDementia
No FDA-
approved drug therapies
currently
available
Cholinesterase
inhibitors
Cholinesterase
inhibitors
NMDA-
antagonists
Cholinesterase
inhibitors
NMDA-
antagonists
Pharmacological InterventionsMedication Side effects
Acetylcholinesterase inhibitors:
Donepezil (Aricept)Rivastigmine (Exelon)
Galantamine
DiarrheaLoss of appetite/weight loss
NauseaSyncope
BradycardiaConfusion
DizzinessInsomnia or Hypersomnolence
FatigueHeadache
Memantine (Namenda) SyncopeConfusion
DizzinessHeadache
Diarrhea or ConstipationVomiting
Hypertension
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Benefit to Current Dementia Medications
• “Boost” memory
- Perform same or better on memory tests for next 6-12 months
- After 6-12 months, decline
• Patients may feel sharper
• May seem less confused, participate more in activity
• May maintain ADL 6-12 months longer
Therapeutic Gaps
• Drugs do not delay progression
• No new drug since 2003
• No FDA Therapy approved for MCI
• Currently available medications have many known common side effects
• Therefore, there is a need for
nonpharmacological interventions
NonpharmacologicalInterventions
• Most evidence for:
- Physical activity
- Cognitive exercises
- Socialization
- Mediterranean diet
NonpharmacologicalInterventions
• Caveats
- There is a paucity of high-quality literature exploring these interventions
- Small sample sizes
- Short-term follow-up periods
- Highly variable interventions
Physical Activity
• Increases cerebral blood flow, primarily in the frontal lobe
• Lower levels of inflammatory markers in the brain
• Lower levels of brain A-beta protein
• Increased hippocampal volume
Physical Activity
• Overall benefits
- Decreased risk of developing chronic degenerative diseases that increase risk of dementia
- Increased functional capacity
• Slower rate of functional decline in dementia patients who participate in exercise interventions
- Reduced sarcopenia
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Exercise in persons with Mild Cognitive Impairment
• 469 persons, 75+, NYC
• 124 developed dementia over 5 yrs
• Lower risk w/ leisure activities of
- Reading
- Dancing
- Playing board games
- Playing musical instruments
Verghese. NEJM. 2003
2004 National Dance Council of America !!
Dancing away the years
Answer: activity at all ages
Mi Hujo18 años; yo mismo 50 años
70 años
Physical Activity:2004 Meta-Analysis
• 30 RCTs including 2020 adults >65 yo with cognitive impairment
- Mean training duration – 23 weeks
- Average 3.6 sessions per week and 45 min/session
- Predominantly aerobic (i.e. walking) interventions
• 12 of the included studies looked at cognitive outcomes
Hayn. Arch PMR. 2004
Physical Activity:2004 Meta-Analysis
• Results:
- Exercise group showed improvements in cognitive tasks compared to control
Hayn. Arch PMR. 2004
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Physical Activity:2014 Systematic Review
• 4 RCTs of exercise interventions in cognitively impaired adults
• Exercise interventions took place over 12-24 weeks
• Interventions ranged from 3 to 7 sessions per week
Farina. 2014 Farina. 2014
Physical Activity:Other Findings
• High intensity exercise c/w stretching control ���� ↑ executive functioning (Hahn
& Andel and Baker, et al)
• 1 year Tai Chi program reduced rate of progression to dementia c/w stretching control group (Lam, et al)
• 6 month exercise group c/w normal activity control group ���� ↑ cognition sustained at 18 months (Lautenschlager)
Cognitive Exercises
• Cognitive stimulation:
- group activities to increase cognitive and social operation
• Cognitive training:
- teaching techniques to improve cognitive function
• Cognitive rehabilitation:
- individualized programs to target specific activities of daily life
Cognitive Interventions
• Goal
- Optimize function and well-being
- Minimize disability
- Prevent malignant social interactions
- Attempt non-pharmacologic intervention for cognitive impairment
• Historically, main focus is memory
• Differs from other interventions that target behaviors, emotions or physical function
Cognitive Exercises
• Forms available
- Computerized interventions/games (i.e. Lumosity)
- Video games (i.e. Nintendo Brain Age)
- Senior classes
- Cognitive “hobbies” (ie. crossword puzzles, sudoku, reading)
- Cognitive training with use of therapy
• Compensatory vs. restorative techniques
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Cognitive Exercises:2006 Meta-Analysis
• Aim: review literature on cognitive interventions and evaluate the effect on cognition and function
• Included 19 studies described in 17 articles –
- All subjects had a diagnosis of AD or probable AD
- 14 of 19 were randomized controlled trials
- 12 studies used primarily restorative techniques
- 7 studies used primary compensatory techniques
Sitzer. Acta Psychiatr Scand. 2006
Cognitive Exercises:2006 Meta-Analysis
• Results
- Overall mean effect size for all cognitive training strategies was 0.47
- Restorative approaches had higher mean ES than compensatory approaches but not significantly different
- Findings were similar when analyses were performed on the 5 highest quality studies but effect sizes were smaller
- Benefits were maintained for an average of 4.5 months
Sitzer. Acta Psychiatr Scand. 2006
Sitzer. Acta Psychiatr Scand. 2006
Cognitive Exercises:2006 Meta-Analysis
• Interpretation
- Overall there cognitive therapies can lead to improvement in cognitive and functional abilities in AD patients
- Benefits may have at least a brief lasting effect
Sitzer. Acta Psychiatr Scand. 2006
Cognitive Exercises:Other Findings
• 2012 Cochrane Review of cognitive stimulation in dementia
- Improved cognitive function in patients receiving cognitive stimulation and reality orientation that was sustained 3 months post-intervention
- Improved self-reports of QoL and well-being
- Improved communication and social interaction as noted by others
Socialization
• Engagement in group activities
• Regular conversation
• Support groups
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Socialization
• Disengagement is a risk factor for cognitive impairment and is associated with depressive symptoms
• Small quantity and low quality of social relations is associated with increased risk of death (House as cited in Fratiglioni)
Socialization: 2011 RCT
• Aim: study the impact of a socialization intervention on cognition in “lonely”elders
• Intervention: social group activities 1x/week for ~6 hours for 3 months
• Participants: elders who self-report loneliness, MMSE >19, CDR </= 1
Pitkala. AJGP. 2011
Socialization: 2011 RCT Results
• ADAS-cog was performed at baseline and 3 months
- Improved significantly more in the intervention vs. control group
• 15D measure of HRQoL measured at baseline and 1 year
- Significant difference with higher levels in the intervention group at 1 year
- Within the dimension of “mental function”, significant improvement in the intervention group only
Sitzer. Acta Psychiatr Scand. 2006
Socialization: 2011 RCT
• Socially stimulating activities in lonely elders may help to improve cognition
Sitzer. Acta Psychiatr Scand. 2006
Multimodal Approaches
• Interplay among the intervention strategies discussed
- Many programs are done in a group setting
- One-on-one instruction provides social engagement
- Many programs provide multiple forms of stimulation
Multimodal Approaches
• A small study tested a multimodal method of PE, cognitive interventions and community activities
- Those who participated the longest in the intervention had no significant change in CDR, MMSE score or other tests of cognition between years for the 4 years studied
Arkin. Am J of Alz Disease
and Other Dementia. 2007
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Accessing These Interventions
• Physical activity
- Silver sneakers
- Fitness centers
- Outside activities (weather-permitting!)
- Senior dance classes
Accessing These Interventions
• Cognitive interventions
- Cleveland Brain Emporium
- Occupational therapy
- Speech Therapy
- At home activities (games, puzzles, electronic resources, reading, school books, etc.)
Accessing These Interventions
• Socialization
- Senior centers located throughout the community
- Local churches, temples
- Support groups
- Volunteer opportunities
Other Interventions
• Support groups for patients and caregivers
- One study: support groups ↓ risk institutionalization (Spijker)
Dietary Modification
• Vitamin E
• Beta-carotene
• Vitamins B6, B12, and folate
• Vitamin D
• Ginkgo biloba
• Cholesterol and fatty acid
• Alcohol
• Mediterranean diet
Vitamin E andMild-Moderate AD
• 613 veterans 2007 – 2012
• Randomized to:
- Vit E (α tocopherol)
- Memantine
- Vit E + memantine
- Placeo
• Outcome: ADL score
• Result: Vit E better than placeboSano. JAMA. 2014
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Vitamin E and Risks
• No benefit, maybe reduced cognition (Lloret 2009, very small study)
• Increased risk bleeding with warfarin in AF (Pastori. JAHA 2013)
• No effect on cancer, CVD, or mortality- Fortmann. USPSTF 2013
• Vitamin E > 22 U: increased mortality slightly
(RR 1.03, CI 1 – 1.05) Bjelakov. PLOS1 2013
Vitamin E Mortality: probably increases with dose!
Miller. Annals IM. 2005
2000 Units
Vitamin E Units/ day
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Mediterranean Dietdelays onset of dementia
• Eating primarily plant-based foods- fruits and vegetables, whole grains,
- legumes and nuts
• Replacing butter with healthy fats- olive oil and canola oil
• Reduce sodium- herbs and spices to flavor foods
• Limiting red meat- no more than a few times a month
• Eating fish and poultry at least twice a week
• Drinking red wine (no more than 1 / d)
Mediterranean diet assoc w/ reduced risk AD
“Predimed” and cognition
• 522 persons mean age 74.6
• Non-demented
• Randomized, followed x 6.5 years
- MedDiet w/ EVOO or MedDiet w/nuts
- Control low-fat diet
• Result: Cognition better with
- MedDiet w/EVOO or nuts c/w low-fat
- Differences tiny
Martinez-Lapiscina. Cog Neuro. 2014
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NonpharmacologicalInterventions
Benefits
• Theoretically easily to implement
• Readily available in the community
• No side effects – low risk, high reward
• Can be used at any stage of cognitive impairment
Potential Barriers
• Denial or unawareness of memory deficits
• Difficulty following tasks
• Apathy
• Cost
• Limited perceived value of task
Healthy Lifestyledelays progression of cognitive
impairment
• Social Life
• Mental Engagement and Education
• Physical Activity
• Mediterranean diet
Questions?