Dementia Assessment: Delaying Progression. Agatha Christie Queen of Crime! Murder on the Orient Express Agatha Christie Age 44

Transcription

1 Dementia Assessment: Delaying Progression Who is this? September 15, 2014 BJ Messinger-Rapport, MD Cleveland Clinic Agatha Christie Queen of Crime! 1 st novel: Mysterious Affair at Styles (Poirot) Last novel she wrote: 1973 Postern of Fate Dame Commander of the British Empire Murder on the Orient Express Agatha Christie Age Mystery Writers of AmericaGrand Master Award 1926 Murder of Roger Ackroyd 1934 Murder on the Orient Express Her 80 s Alzheimer Disease B: 1890 England D: 1976 Age years old Postern of Fate What do you see in 1973 compared with 1934? Creative Desire to contribute Rambling Paucity of words Simpler ideas 1

2 What Is Dementia? Cognition? 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 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? Stages of dementia 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 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! 2

3 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 Typical occurrence of manifestations of Alzheimer's disease. Late onset dementia- influence only ApoE e4 - Onset, intensity influenced by Lifestyle, comorbidities Sloane, AAFP,

4 Mild Cognitive Impairment 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) U of California Irvine ADRC NONE COLLECTED TYPICALLY DURING ROUTINE CARE Risk Factors for worsening cognitive impairment Medical conditions associated with impaired cognition Fixed Male Advanced age Lower Education APOEe4 genotype Potentially Modifiable Smoking, alcohol Lifestyle - Socialization - Cognitive stimulation - Physical exercise Diet Certain drugs Vascular disease Medical conditions Sleep apnea Atrial fibrillation Heart Failure Diabetes Stroke Hypertension Mild Cognitive Impairment No FDAapproved drug therapies currently available Pharmacological Interventions Mild Dementia Cholinesterase inhibitors Moderate Dementia Cholinesterase inhibitors Severe Dementia Cholinesterase inhibitors NMDAantagonists NMDAantagonists Pharmacological Interventions Medication Acetylcholinesterase inhibitors: Donepezil (Aricept) Rivastigmine (Exelon) Galantamine Memantine (Namenda) Side effects Diarrhea Loss of appetite/weight loss Nausea Syncope Bradycardia Confusion Dizziness Insomnia or Hypersomnolence Fatigue Headache Syncope Confusion Dizziness Headache Diarrhea or Constipation Vomiting Hypertension 4

5 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 Nonpharmacological Interventions Most evidence for: - Physical activity - Cognitive exercises - Socialization - Mediterranean diet Nonpharmacological Interventions 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 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 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 5

6 Exercise in persons with Mild Cognitive Impairment Dancing away the years 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 National Dance Council of America!! Answer: activity at all ages 70 años Mi Hujo18 años; yo mismo 50 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 Physical Activity: 2004 Meta-Analysis Results: - Exercise group showed improvements in cognitive tasks compared to control Hayn. Arch PMR

7 Physical Activity: 2014 Systematic Review 4 RCTs of exercise interventions in cognitively impaired adults Exercise interventions took place over weeks Interventions ranged from 3 to 7 sessions per week Farina Farina 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 7

8 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 Cognitive Exercises: 2006 Meta-Analysis Results - Overall mean effect size for all cognitive training strategies was 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 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 Sitzer. Acta Psychiatr Scand 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 wellbeing - Improved communication and social interaction as noted by others Socialization Engagement in group activities Regular conversation Support groups 8

9 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 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 Socialization: 2011 RCT Socially stimulating activities in lonely elders may help to improve cognition Sitzer. Acta Psychiatr Scand Sitzer. Acta Psychiatr Scand Multimodal Approaches 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 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

10 Accessing These Interventions Physical activity - Silver sneakers - Fitness centers - Outside activities (weatherpermitting!) - 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 and Mild-Moderate AD 613 veterans Randomized to: - Vit E (α tocopherol) - Memantine - Vit E + memantine - Placeo Outcome: ADL score Result: Vit E better than placebo Sano. JAMA

11 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 ) Bjelakov. PLOS All cause mortality risk difference Vitamin E Mortality: probably increases with dose! 2000 Units Vitamin E Units/ day Miller. Annals IM Mediterranean Diet delays 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

12 Benefits Nonpharmacological Interventions 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 Lifestyle delays progression of cognitive impairment Social Life Mental Engagement and Education Physical Activity Mediterranean diet Questions? 12