Assessing and Managing the Patient with Cognitive Decline Center of Excellence For Alzheimer s Disease for State of NY Capital Region Alzheimer s Center of Albany Medical Center Earl A. Zimmerman, MD Professor of Neurology
Support Grant support from NYS Department of Health for Center of Excellence in Alzheimer s disease for the NY Capital region 2016-2021 IDMC member (Independent Monitoring Board) for vtv Therapeutics phase 3 trial of TTP488 (alzeliragon) 2015-2018 in mild AD PI at AMC for Biogen phase 3 trial of monoclonal antibody aducanumab in MCI/early AD 2016-2018
Objectives *Learn simple methods to detect early dementia, or recognize even if not so early. *Be aware of tools to measure dementia in the patient in the office. *When to refer to neuropsychology or a specialist. *What imaging techniques are better? *What treatments and when?
Common Progressive Cognitive Disorders Alzheimer s disease more than 70%; presents usually with short term memory loss for years Frontotemporal dementias different disorders most often presenting with frontal behaviors: poor judgment, disinhibition early and language problems Lewy Body disease presents often with early hallucinations, parkinsonism, REM sleep disorder Vascular dementia: Multi-infarct; lacunar strokes; less common nowadays
Why Bother? Pathologies are different and treatments differ. Discovery the earlier the better for AD: MCI, mild cognitive/early AD can be slowed by aerobic exercise; treatment of diabetes and hypertension ameliorates AD Diagnosis of FTD often missed as psychiatric or poor judgement unrecognized may result in financial and other disasters Tighter control of BP and HbA1C may prevent lacunar stroke/dementia
AD Statistics AD is the most common cause of dementia among people age 65 and older. Scientists estimate that around 4.5 million people now have AD. This number is expected to rise to 13 million by 2050. The national cost of caring for people with AD is approximately $100 billion per year More than 70% of patients with AD live at home with care provided by family and friends
Definition of Dementia: Impairment of short and long term memory in addition to abnormalities in at least one area of mental function: o o o o o o Abstract thinking Judgment Praxis Visual recognition Constructional abilities Personality
Causes of Dementia (Progressive Mental Decline) Alzheimer s disease (50-75%) Frontotemporal dementia (FTD) (Picks complex) (10-15%) Lewy body dementia (LBD) (5-10%) Parkinson's disease CJD (Creutzfeldt-Jakob/ prion disease) (rapid, rare) Cerebrovascular dementia (multi-infarct) (10%) Dementia with Multiple Sclerosis (MS) Dementia with treatable cause Pseudo dementia (depression often coexists with AD) Normal pressure hydrocephalus Brain tumor Hypothyroidism Vitamin B12 deficiency Infection: AIDS, syphilis
Different Presentations of Dementia Short term memory loss is the most common Visual spatial issues Language issues
Tau support for microtubule integrity and function is lost in AD due to A-beta amyloid or in FTD due to Genetic or other defects
Alzheimer s disease timeline Genetic risk Factors? Mis-folding & aggregation of aβ & tau, followed by sps & nfts Oxidative, nitrative & inflammatory Damage Cell death Clinical Diagnosis Autopsy MCI Probable AD Yrs. 0 20 40 60 80 100 Preventative Modifying Symptomatic
Stages of Alzheimer s Disease Clinical Dementia Rating Scale (CDR) MCI (Mild Cognitive Impairment) Mild Stage (CDR1) Moderate Stage (CDR 2) Severe Stage (CDR3)
MCI (Mild Cognitive Impairment) New research category- not a disease Usually people with memory complaints and sometimes other things like word finding Function normally in Activities of Daily Living (ADL s) When tested, memory is slightly abnormal for age and education The memory type of MCI (amnestic) are more likely to progress to AD (rate of 10%/year) This is the subject of intense research interest for determining who with MCI has early AD and what might be done to stop progression
Clinical Progression of AD Early Stage (Mild) Pre mild - MCI: short term memory loss beyond normal aging; not demented (no loss of ability) Mild, stage 1: short term memory loss due to degeneration in hippocampus; mild visual-spatial difficulty (drawing intersecting pentagons on MMSE) due to parietal cortical dysfunction; independent except for forgetting medications, appointments Word finding trouble Often depressed (apathy, loss of interest)
Dennis Selkoe, Scientific American, Plaque distribution in red dots
Stages of AD (Moderate) More extensive memory loss More visual-spatial difficulty (visual agnosia): wandering, lost in space; need guidance in ambulation; some become delusional and others become agitated ( sundowning ) May become hypersexual and may crave sweets due to involvement of amygdala More trouble with language (aphasia) Parkinsonism in 25%
Stages of AD (Severe) Develop gait apraxia due to frontal cortex loss ( feet stuck to the floor ) forget walking Exhibit grasp reflexes Lose all language Become bedridden and need total care Later have trouble swallowing Die from aspiration pneumonia Hospice for last 6 months
AD8 Scale Quick, easy, and reliable for early detection of dementia Takes a few minutes Can be done by patient, but less desirable Score of two or greater suggests dementia Highly recommended for screening
Next Steps Administer the MMSE or MiniCog
MMSE Scoring Score of 26 or less out of 30 may suggest dementia Score of 10-20 our of 30 c/w moderate stage AD Score less than 10 c/w severe stage and test is not reliable due to language loss Not sensitive in early stage AD (MCI or very early AD)-Suggest performing MoCA
Mini COG
Imaging MRI of the brain (without contrast) if possible is preferable to CT scan o Better detail to detect atrophy and vascular disease Actual scan should be provided to consulting neurologist at first visit as well as report Caregiver/informant is critical for assessment
Advanced Imaging Metabolic PET/CT o To look at glucose metabolism loss. o May be useful in MCI or very early AD. Determining AD from FTD o Expensive and generally not needed (insurance may not cover) Amyloid PET o Useful especially in early diagnosis but CMS not paying for it o Research tool at present
Initial Management Complete evaluation before using medication Depression usually apathy is typically part of the presentation even in MCI and early AD o Patient benefit more from an SSRI than Aricept/Namenda. Both SSRI and Aricept (donepezil) can cause diarrhea o Don t start both at the same time Cholinesterase inhibitors and memantine both can cause agitation and DO NOT slow progression Aerobic exercise does o I recommend 30min/day, five times/week if possible in early stage AD
When to Order a Formal Neuropsychological Evaluation? The diagnosis of AD is clinical and not by neuropsychological testing The clinical testing should be done first most like by a neurosciences clinician expert in the diagnosis: evidence for progressive change from an informant, formalized office testing of patient, family history, clinical examination: r/o stroke, evidence for apraxia, parkinsonism, atrophy on the MRI Generally neruopsych should be ordered for very early AD (MCI) or differential diagnosis: AD vs FTD or LBD or for year repeat for advanced progression
What can our center do for you, primary care? Fully evaluate/diagnose dementia and its causes Educate the caregiver and family. Social work services are present from the initial visit Recommend a treatment course in collaboration with your general management of the diseases of aging. o Example: Maximize BP and diabetes control Follow patients longitudinally and help manage the behaviors and care issues long term.
Tools/Scales MMSE (Mini Mental Status Exam) MoCA (Montreal Cognitive Assessment) o o Much more sensitive especially in MCI/early AD; Takes experience and longer time ADL/IADL (Activities and Instrumental Activities of Daily Living) o Completed by caregiver CDR (Clinical Dementia Rating Scale) o o o o Useful tool in explaining to family the stage of the disease and in what is expected in 10 years CDR: 1 Mild stage, 5 years CDR: 2 - Moderate stage and more dependent, 3 years CDR: 3 - Severe stage, about 2 years. Neuropsychiatric inventory o Excellent way to understand behaviors. Mores useful than Geriatric depression scale
Common Mistakes in AD Failure to recognize memory loss resulting in medication mix-ups Unrecognized depression in early management Patient drifts into moderate AD and has an auto accident or wanders off Develops psychosis and goes after his wife with a butcher knife in unrecognized moderate AD Financial disasters due to poor judgment even in fairly early AD
Psychosis in Moderate AD Occurs to some degree in up to 40% of our patients Agitation most common and hallucinations in some and sometimes combativeness especially at dinner time ( sundowning ) We explain to family the use and risks of atypical antipsychotics and titrate them and monitor them. Can allow patient to stay at home. Quetiapine is more sedating but has less side effects and tends to be more effective.
End of Life Issues Educate family on the dying process Recruit palliative/hospice care for late stage Death Certificate o o Put Alzheimer s disease as the first diagnosis (the underlying disease process Highly under reported Second diagnosis: pneumonia or cardiopulmonary arrest.
Alzheimer's Center of Albany Medical Center NYS Center of Excellence for Alzheimer s Disease (CEAD) Diagnosis and Care Plan Case Management with Goldberg Alzheimer s Resource Research in Biomarkers and Drug Trials of industry and NIH, e.g. The ADNI imaging project; Biogen phase 3 trial of monoclonal antibody zimmere@mail.amc.edu; (518) 262-0800