Primary Care Update January 28 & 29, 2016 Alzheimer s Disease and Mild Cognitive Impairment

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1 Primary Care Update January 28 & 29, 2016 Alzheimer s Disease and Mild Cognitive Impairment Kinga Szigeti, MD Associate Professor UBMD Neurology UB Department of Neurology

2 Questions How do we differentiate normal aging from amnestic mild cognitive impairment from early Alzheimer s disease? When do we start treatment and what is the expected outcome of the treatment/ How long do we treat?

3 DIFFERENTIAL DIAGNOSIS OVER TIME Early AD: normal aging and MCI --- continuum Later: the other dementias Limited tools: no specific diagnostic test except pathology Probabilistic diagnosis

4 Epidemiology Common Incidence doubling every 5 years over 65 Women (likely longevity) Millions Projected prevalence of AD No intervention 2 year delay 5 year delay In the context of aging: Meta analysis of cognitive impairment prior to AD diagnosis Global functioning Episodic memory (largest effect delayed recall) Perceptual speed Executive functioning Still under research available normative data likely contaminated with MCI

5 Mild cognitive impairment (MCI) Petersen Criteria Cognitive complaint (usually memory) (informant) Cognitiveimpairment (usually memory) for age and education (neuropsych testing Z-score -1.5) Normal general cognitive testing Largely preserved activities of daily living Not demented Amnestic Non- Amnestic Single domain Muti domain Single domain Muti domain Conversion to AD Degenerative Vascular Psych AD Depression AD VaD Depression FTD Psychiatric DLB VaD Psychiatric 1-25 % per year in various studies Likely methodological differences All MCI versus amnestic MCI only Amnestic MCI: 25 % per year

6 NINCDS-ADRDA Criteria Probable AD Deficits in two or more domains of cognition Memory Language Perceptual skills Attention Constructive abilities Orientation Problem solving Functional abilities Clinical symptoms Cognitive screening tests Neuropsychological testing Progressive decline of memory and other cognitive functions Preserved consciousness Onset between ages 40 and 90 Clinical evaluation Absence of systemic or other brain disease that could account for symptoms Clinical evaluation Imaging, laboratory screen for correctable causes of dementia

7 The diagnosis of dementia due to Alzheimer s disease: Recommendations from the National Institute on Aging and the Alzheimer s Association workgroup Amnestic presentation: Most common Impairment in learning and recall of recently learned information At least one other cognitive domain Nonamnestic presentations: Language presentation: prominent deficits are in word-finding Visuospatial presentation: prominent deficits are in spatial cognition object agnosia impaired face recognition simultanagnosia alexia Executive dysfunction: prominent deficits in reasoning, judgment, and problem solving Reference: Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2011;7(3):

8 ALZHEIMER DISEASE: DEFINITIONS, LEXICON Dual clinico-pathological entity Biomarkers Dual clinico-biological entity The clinico-pathological diagnosis implies a probabilistic approach ante mortem

9 Single Domain Amnestic Red-yellow = diff small-diff big Multidomain Z score <-2 Mild AD MMSE 20-26

10 PET METABOLISM AND AMYLOID IMAGING

11 AD Treatment Cholinesterase inhibitors NMDA receptor antagonist Modifiable risk factors Correctable causes BPSD

12 AD: CHOLINESTERASE WHICH CHOLINESTERASE INHIBITOR? FDA APPROVED FOR MILD TO MODERATE AD Side effects: nausea, vomiting, diarrhea Donepezil (Aricept) Once a day High dose studied Vivid dreams: morning dosing Rivastigmin (Exelon) Pseudo-irreversable inhibitor More side effects Patch option Galantamine Nicotinic receptor too Theory: additional benefit Reality: no additional benefit, but cardiac death more DONEPEZIL IN AMCI

13 Memantine: FDA approved for moderate stage

14 Discontinuation of Drugs 295 communitydwelling patients Treated with donepezil for at least 3 months Moderate or severe Alzheimer's disease 4 arms: continue donepezil discontinue donepezil discontinue donepezil and start memantine continue donepezil and start memantine 52 weeks Coprimary outcomes SMMSE Bristol Activities of Daily Living Scale

15 Symptoms of Dementia Apathy Agitation Anxiety Depression Sleep disturbance Psychosis Disinhibition Hallucinations Delusion: paranoid, unfaithful, misidentification Often the most significant problem for caregivers

16 Catie-AD Trial Adverse Affects Offset Efficacy FDA black box warning: Increased risk of death and stroke

17 Management of BPSD Often related to changes in caregiver, surroundings Measure: e.g. NPI Try non-pharmacological intervention first Distraction Redirection Exercise Atypical antipsychotics: periodic reassessment and attempt to taper

18 Resources UBMD Alzheimer s disease and Memory Disorders Center a NYS Center of Excellence for Alzheimer s Disease Alzheimer association WNY Chapter

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