Alzheimers+Prognosis

Functional Implications of Alzheimer’s Disease Search Terms
 * Pubmed and google scholar were the only comprehensive review sources used by all
 * Boolean term used: AND
 * Search Terms: Alzheimer’s, prognosis, functional tests, tests, exercises.
 * Any combination of these terms was searched for more than once by different researchers. Varying levels of evidence were found and included in the project ranging from systematic reviews to quasi experimental (control vs. Alzheimer's) studies.

Clinical Question What does the progression of Alzheimer’s look like, and do exercise and pharmaceutical interventions help reduce the symptoms?

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What is Alzheimer’s? According to the Alzheimer’s Association: “Alzheimer's is a type of dementia that causes problems with memory, thinking and behavior.Symptoms usually develop slowly and get worse over time, becoming severe enough to interfere with daily tasks.” In addition to this catch-all quote, it mentions that Alzheimer’s is a progressive disorder that gets worse over time as we age and currently has no cure, but symptoms can be treated [1]

Why is Alzheimer's Important to discuss?
 * About 46 million people are living with dementia worldwide
 * Every 3 seconds 1 person is diagnosed with Dementia throughout the world
 * ~ 9.9 million new cases diagnosed annually
 * Every 66 seconds 1 person will develop dementia in the United States
 * In 2015 an estimated 18.1 billion hours of unpaid care was provided
 * Family caregivers can easily spend more than $5,000 a year on care
 * In 2016, Alzheimer’s and other dementias are estimated to cost the United States $236 billion [2]

Tests, Pathology, and Cellular Level Effects
 * __There is no one single exam that can determine the diagnosis of Alzheimer’s. __** This is done through a thorough medical history, the patient's age, and any number of the following tests
 * **Mini-mental state exam (MMSE) **
 * **Eye examination **
 * **Speech Tests **
 * **“Mini-Cog” **
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Clinical dementia rating scale **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Reflex and sensation may also be tested, though there are no specific indications found with these types of tests [3]

Various Tests of Cognitive Function
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Rapid Evaluation of Cognitive Functions Test, Symbol Digit Test,Verbal Fluency Test, Trail Making Test, Wechsler Memory Scale revised, Verbal Learning Memory Test, and Rivermead Verbal Learning Test
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">As you can see, there are a number of tests, but we’ve decided to go into more detail about the specific ones that are typically used as part of the diagnosis listed on the previous slide

Mini-Mental State Examination (MMSE)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">During the MMSE, a health professional asks a patient a series of questions designed to test a range of everyday mental skills
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">The maximum MMSE score is 30 points. A score of 20 to 24 suggests mild dementia, 13 to 20 suggests moderate dementia, and less than 12 indicates severe dementia. On average, the MMSE score of a person with Alzheimer's declines about two to four points each year [3]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Here’s a Link to the Exam itself: https://www.mountsinai.on.ca/care/psych/on-call-resources/on-call-resources/mmse.pdf

Eye Examination
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Optical Coherence Tomography **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Has been used clinically for Diagnosis of Glaucoma and Macular Degeneration
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Has biomarkers specifically for Mild Cognitive Impairment and AD
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">AD damages the Lateral Geniculate Nucleus and areas of the primary visual cortex and associated structures
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">AD also damages retinal ganglion cells which is also likely correlated with damage to the optic nerve caused by changes due to AD (neurofibrillary tangles). These tangles also seem to affect processes of the visual cortex even if they’re not located in that area of the brain [4]

Speech Test
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">The “Set-Test” **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">“The set-test evaluates the verbal fluency in 4 categories: colors, animals, fruits and cities. It has been proposed as a diagnostic aid in dementia in elderly patients...It had a positive correlation of 73 with mini-mental test. The cut-off value was 29 in adults and 27 in elderly people. A lower score is indicative of dementia. Sensitivity was 79% and specificity 82%, with 20% of incorrectly classified patients” [5]

“Mini-Cog” <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">During the mini-cog, a person is asked to complete two tasks:
 * 1) <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Remember and a few minutes later repeat the names of three common objects
 * 2) <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Draw a face of a clock showing all 12 numbers in the right places and a time specified by the examiner [3]

Clinical Dementia Rating Scale
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Developed primarily for Alzheimer patients and it is also used to stage dementia in other illnesses
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Five-point scale
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">0 = no cognitive impairment
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">0.5 = very mild dementia
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">1 = mild dementia
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">2 = moderate dementia
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">3 = severe dementia
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Six domains are:
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Memory
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Orientation
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Judgment and Problem solving
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Comunity affairs
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Home and Hobbies
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Personal Care
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Assesses the patient’s cognitive ability to function in these areas <span style="font-family: 'Times New Roman',serif;">[6]

Cellular Level Effect
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Level of Amyloid Beta Plaque (present in older people most of the time)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Tau Protein in CSF increase (not present normally in CSF)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Number of Neurofibrillary Tangles-Necrotic Tau protein(not present normally)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Decline in CSF AB42 gene [8]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Various Gene Levels increasing or decreasing

Specific Genes for Alzheimer's? Not so much.. <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">“Risk genes: While there is a blood test for APOE-e4, the strongest risk gene for Alzheimer's, this test is mainly used in clinical trials to identify people at higher risk of developing Alzheimer's. Carrying this gene mutation only indicates a greater risk; it does not indicate whether a person will develop Alzheimer's or whether a person has Alzheimer's” [9]

Pathology
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Hippocampus (memory) Size Decrease
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Brain Ventricle Size Increase
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Cortex Size decreases [7]



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Types of AD
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">sAD (sporatic)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">fAD (familial) or Autosomal dominant Alzheimer’s Disease (ADAD)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">LOAD (late-onset)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">AR-AD (asymptomatic at-risk)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Can belong to one or more of these groups at a time! [8]

AR-AD <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Using some of those things mentioned in the previous slides to categorize someone who is asymptomatic with Alzheimer's, but essentially it’s based on one criteria; whether or not the amyloid plaques and tau proteins are present in the brain. Many researchers believe that this alone is enough to diagnose someone with AD [8]
 * Preclinical Alzheimer's: **

Progression [10,11]
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Stage 1: Early Stage **
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Stage 2: Middle Stage **
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Stage 3: Late Stage **

Stage 1: Mild Alzheimer’s (Early-Stage) [10,11]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Duration: 2-4 years **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">May still maintain functional independence (drive/social)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Occasional memory lapses
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Friends/family begin to notice difficulties
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">During a detailed medical exam, doctors would likely detect
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Memory losses or concentration difficulties


 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Examples Include: **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Problems coming up with right word or name
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Social life and work is beginning to become hindered
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Losing/misplacing objects
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Forgetting material just presented to them

Stage 2: Moderate Alzheimer’s (Middle-Stage) [10,11]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Duration: 2-10 years [[image:carla 6.jpg align="right"]] **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Greater level of care required
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Unexplained behavior occurs
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">More emotions expressed
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Damage to nerve cells increases difficulty to perform tasks and communicate thoughts
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Examples: **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Forget past details about own life
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Feeling moody/withdrawn
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Increased wandering/feeling lost
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Trouble controlling bladder/bowels
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Compulsive behavior. Getting angry or frustrated when confusing words

Stage 3: Severe Alzheimer’s (Late-Stage) [10,11]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Duration: 1-3 years **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Loss of ability to respond environment
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Can no longer carry out full conversations
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Movement impairment
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Memory and Cognitive skills decline significantly
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Full time care required (24/365)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Required high levels of assistance with ADLs/personal care
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Loss of awareness in surroundings
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Vulnerable to infections; specifically pneumonia

Predicting the progression of Alzheimer’s disease dementia: A multi domain health policy model [12]
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Purpose: **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;"> Demonstrate the utility of a multidomain approach to modeling progression of AD and provide a foundation from which to develop a model to support the health policy context
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">3009 Participants. Requirements were: **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">MMSE score of 26 or less
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Age 50 or above
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Continuous data collected over time on at least two consecutive assessments
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Outcome measures **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Multi-Mental State Examination (MMSE)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Functional Assessment Questionnaire (FAQ)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Neuropsychiatric Inventory (NPI)
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Conclusion: **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Over a 5 year period, it was found Mild AD mortality risk = 5%. Progressing to Moderate inc. to 48%. Additional inc. to 83% severe AD

10 Signs and Symptoms of Alzheimer’s [11]





Treatment for Symptoms

Pharmaceuticals
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Acetylcholinesterase Inhibitors- for memory loss **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Galantamine
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Donepezil
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Rivastigmine
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Memantine
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Ginkgo biloba
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Not approved by the FDA, but currently used in Europe
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Antipsychotic drugs **<span style="font-family: 'Times New Roman',serif; font-size: 12pt;">-for aggressive behavior
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Memantine **<span style="font-family: 'Times New Roman',serif; font-size: 12pt;">-NMDA receptor blockers, typically this receptor binds glutamate which in excess can cause cell death

Systematic Review on Drug Treatment [13]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Included 31 studies and 9,611 subjects
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Standardized Mean Change score using Raw score standardization (SMCR) of cognitive performance were calculated
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">This allowed the authors to compare studies that used different cognitive/functional tests as the outcome measure
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Analyzing the five available drugs in AD, there is a small but statistically significant difference, favoring drug over placebo (SMCR: 0.23, 95% confidence interval [CI]: 0.20–0.25)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Tests for Heterogeneity: Q (df= 58) = 195.04, p<0.01; I2= 72.12%
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Test for Overall Effect: Z= 33.86, p<0.01



Cognitive and Functional Decline and Their Relationship in Patients with Mild Alzheimer's Dementia [14]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">**Purpose:** Assess the relationship between cognitive and functional decline and the relationship between cognitive and functional treatment effects in patients with mild AD
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">2 groups **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">1 group received 400-mg of solanezaumad (664)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">1 group received a placebo (660)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Every 4 week for 18 months
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Outcome measures **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">AD Assessment Cognitive Scale
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">AD Cooperative Study -Activities of Daily Living
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Conclusion: **
 * <span style="font-family: Times New Roman,serif;"> Congnition declines precede functional declines, and that in slowing cognitive decline you can slow functional declines as well

Exercise Program for Nursing Home Residents with Alzheimer's Disease: A 1-Year Randomized, Controlled Trial [15]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">**Purpose**: determine if a 12 month exercise program could reduce ADL declines in individuals who were diagnosed with with Alzheimer’s Disease (AD)
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Randomized controlled Trial **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">5 nursing homes
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">134 patients with mild to moderate AD
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">1 group received standard medical care (67)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">1 group participated in exercise program (67)


 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Intervention **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Exercise: 1 hour twice a week with at least 2 days in between sessions
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">88 sessions
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Supervised by an OT
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Groups of 2-7 people
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Exercise Program [[image:https://lh3.googleusercontent.com/dUJqs_CXA7bfFdljWYAWkcyLRFc6cfck6l8ksmLvVqIsC26pl9b-fA-_QMv_i2JoOZiL9bdnmHdumF-629rVVHC-JxMxwxfoGXtIYLpV41yKGB0UWmHiMKb_6VMSntUqGs6D81p429A width="324" height="146" align="right"]]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Aerobic
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Strength
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Flexibility
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Balance
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Program Requirements **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Walk for at least 30min
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Then 30min of strength, balance, and flexibility
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Strength: **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Focused mainly on Lower Extremity
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Squats or sit to stands
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Standing lateral leg elevations and heel raises
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Flexibility **[[image:https://lh5.googleusercontent.com/9xQjsJrLMx_VNm7SP3dWa13wa1K7AIc9IVcawjcQiJJbFTjDhHa6_DZDdiAz-_lLyIyeTbNWP2C9Nv-rBHqNBWXA2glak7pg2V_K_Qka3b959o0ncsqLjpuv5uaw7QxfYIkduP00eYQ width="202" height="181" align="right"]]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Patients mirrored exercises demonstrated by OT
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Balance **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Step drills with cones and hoops
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">1 and 2 legged balance exercises on ground or foam-rubber
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Primary outcome measure **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Katz ADL score
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Secondary outcome measures **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Physical performance: 6m walking test, TUG, one leg balance test
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Nutrition
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Behavior
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Depression
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">110 people completed the study
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Adherence **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">13 completed: > 60 sessions
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">19 completed: 30-60 sessions
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">28 completed: <30 sessions
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">7 completed: 0 session
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">After 12 months, mean ADL score was significantly lower in exercise group (P =.02) than in standard medical care group
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Significant increase in walking speed at 6 and 12 months for the exercise group compared to the standard medical care group



Effects of Exercise on Cognition: The Finnish Alzheimer Disease Exercise Trial: A Randomized, Controlled Trial [16]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">**Purpose:** To see the cognitive effect of a long term exercise program on individuals diagnosed with AD
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">3 groups **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">home-dwelling individuals (70)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Group-based exercise at an adult daycare center (70)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Control group (70)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">12 month program
 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Cognition was evaluated via: **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Clock-drawing test (Part of Mini-Cog)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Verbal fluency
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Mini-mental state examination
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Clinical dementia rating scale
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Physical fitness
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">10 meter walking test




 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">All groups deteriorated in verbal fluency
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Decreased scores on MMSE
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">[[image:https://lh6.googleusercontent.com/aaS2EmSoFBC7l7EYPIPQeQWlMmVFtyqFiaCakarkggj2hu40zJW3uR3bbYGG69qfn1wmivtE1BADqY_ZJfWkDlECqfkYy0tx6GqpZZD4fI7nz14NmmGX1Wimz-fWlAq_EMIHre-KeAc width="278" height="180" align="right"]]No significant findings with:
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Number of sessions attended and change in clock drawing test
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Attending less than half or more than half of the sessions
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Home exercise group
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Mild increase in executive function
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Had to exercise for 12 months until results were seen
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Conclusion:
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Long term exercise program may have some mild cognitive effects, nevertheless, the exercise program enhanced individual's physical functioning and independence

Systematic Review on Exercise Treatment [13]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Included 4 studies and 119 subjects
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Standardized Mean Change score using Raw score standardization (SMCR) of cognitive performance were calculated
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">This allowed the authors to compare studies that used different cognitive/functional tests as the outcome measure
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Exercise had a moderate to strong effect in AD (SCMR: 0.83, 95% CI: 0.59–1.07)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Test for Heterogeneity: Q (df= 3) = 7.82, p= 0.05
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Test for Overall Effect: Z= 6.88, p<0.01

Discussion
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Exercise treatment resulted in moderate to strong effects on cognition in AD [13]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Exercise treatment showed the ability for less deterioration in neuropsychiatric disorders and performance of instrumental activities, better physical functioning, and improved balance and mobility and a reduced risk of falls

Home Modifications [17] <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">“A vast array of strategies that include structural renovation, assistive devices, placement of visual cues and memory aids, and rearrangement or removal of furniture and dangerous household items as well as the simplification of tasks” <span style="font-family: 'Times New Roman',serif; font-size: 12pt;"> <- Mental Aid

<span style="font-family: 'Times New Roman',serif; font-size: 16px;">< Visual Cue

Importance of Caregiver Training/Role [17]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Caregiver takes more responsibility as the care recipient’s cognitive status declined
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Insufficient knowledge/lack of resources resulted in decrease caregiver efficacy
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">After caregiver training and education, caregivers reported 73% of home modifications still in place
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Caregiver Responsibilities: Education of potential hazards, implementation of modifications, aid in social environment of patient

Importance of Caregiver Training/Role [17]

<span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Example: Open Floor Plan

Client Centered Collaborative Approach to Assessment and Intervention [17]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Establish rapport with patient
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Identify the individual needs of patient with AD along with caregiver
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Quite often patient with AD will resist home modifications
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Promote participation and safety

Importance of Environmental Modifications [17] <span style="font-family: 'Times New Roman',serif; font-size: 12pt;"> //Goal: Aiming to improve safety and Function//
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Physical
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Cognitive
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Social

Importance of Environmental Modifications [17]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Physical **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Examples: Wandering off, falls, inattention, poor judgement, medication management, adaptations for temperature, cooking, sharp objects, appliance use
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">71% of caregivers identified unsafe behaviors
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Only 24% took precautions

Importance of Environmental Modifications [17]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Cognitive **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Creative routines and engagement of person with AD
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Setup of task supplies (e.g. simple cooking activities)
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Simplify tasks
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Example: Caregiver engaged her mother (AD) in a gardening activity that was incorporated into their routine

Importance of Environmental Modifications [17]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Social **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Additional support networks
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Verbal Cueing
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Use of Communication strategies



Assistive Devices [18]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">At any point during life, assistance may be necessary to facilitate safe ambulation. When an individual begins to cognitively fail and consequently lose motor control, surely the use of an assistive device will be implemented
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">The decision to begin using an assistive device may be difficult for someone suffering from a degenerative disease such as Alzheimer’s. As physical therapists, we need to be able to gain patients’ trust and educate them on the benefits of an assistive device as well as explain the changes they are experiencing in a way they will understand


 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Some things to take into consideration… **


 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Prior level of functioning **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Due to the progression of AD, the goal of any treatment almost always will not be to regain prior functioning levels. An assistive device should be used to facilitate safe ambulation and to hopefully increase the confidence of the patient and to reduce the decline of the patient as much as possible


 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Current level of functioning **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">From a study done by Muir-Hunter and Montero-Odasso, the use of an assistive device with an individual suffering from AD needs to be considered only if it truly benefits them. Their study found that at a certain point during the progression of AD, the use of an assistive device causes more cognitive stress and in turn dysfunction than actual benefit in ambulation. As physical therapists, we need to be aware of these changes and use our expertise to prescribe the proper device for these patients


 * **<span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Goals **
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">It is always important to discuss the individual goals of each patient. People suffering from any form of dementia may not be cognitively aware enough to interpret their goals, so a discussion with the caregiver may be necessary
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">The main goal of any assistive device is to facilitate safe ambulation and to increase the functioning of the patient. At a certain point in the progression of AD, the use of a wheelchair will most likely be necessary

Education [19]
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Discuss the symptoms listed above and educate the caregiver about the type of AD the patient has
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Discuss the various home modification with the patient and caregiver that will be important and the 3 stages of progression
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Discuss the importance of exercise, if not for the cognitive functioning, at least for the physical and functional aspects that they can improve upon
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Discuss the assistive device usage and attempt to answer any question they have about medications that were not discussed with the diagnosing physician

Summary
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Alzheimer's is difficult to diagnose and done through a combination of medical history and a battery of different cognitive examinations.
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Exercise ≥ 12 months for at least 1 hour twice a week, may have a mild to significant effect on preventing both cognitive and functional decline.
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt; line-height: 1.5;">Include: Aerobic, Strength, Flexibility and Balance exercises
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">The use of an assistive device, although typically helpful, needs to be considered in combination with the cognitive functional level of the patient
 * <span style="font-family: 'Times New Roman',serif; font-size: 12pt;">Exercise needs to be further studied with larger sample sizes, and it also need to analyze effectiveness of different exercise types, exercise intensities, and motivational interventions to increase adherence, as well as patient characteristics

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