dementia diagnosis and_treatment
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Dementia: Diagnosis and Treatment
Debra L. Bynum, MD
Division of Geriatric Medicine
November 2003
Case …
Mr. Jones is a 72 y/o gentleman brought to you by his daughter for progressive memory loss. He denies any problems. She reports that he was an accountant, and is now unable to keep his own check book straight. He has also had difficulty with getting lost while driving to the store. His wife died 2 years ago, and he was diagnosed with depression at that time. In addition, he has HTN and DM. His father was diagnosed with alzheimer’s disease at the age of 85. On exam, his BP is 170/90; he is oriented, scores 26/30 on the MMSE (0/3 recall and difficulty with the intersecting pentagon); he is unable to do the clockface.
A few months later, his MMSE is 24/30; on exam he has some mild cogwheel rigidity and a slight shuffling gate, but no tremor. His daughter reports that he has been having vivid visual hallucinations and paranoid thought…
Questions
1. What are some limitations to the MMSE? 2. Is there any association between HTN and
dementia in the elderly? 3. What are the risk factors for dementia? 4. Would apo E testing be of benefit in this case? 5. What type of dementia might Mr. Jones have? 6. What medications should be avoided with this type
of dementia?
Outline
1. Risk factors and definition of dementia 2. Types of Dementias 3. MMSE and testing 4. Treatment options
Risk factors for dementia
Age (risk of AD 1% age 70-74, 2% age 75-79, 8.4% for those over age 85)
Family hx (10-30% risk of AD in patients with first degree relative with dementia); also cross with parkinson’s with dementia
Head trauma Depression (?early marker for dementia) Low educational attainment? ?hyperlipidemia ?diabetes
Risk factors for AD…
Gender (confounding in literature – women more likely to live longer, be older….)
Down’s syndrome ?estrogen (probably not) ?NSAIDS (probably not)
Cognitive decline with aging
Mild changes in memory and rate of information processing
Not progressive Does not interfere with daily function
DSM Criteria
1. Memory impairment 2. At least one of the following:
– Aphasia– Apraxia– Agnosia– Disturbance in executive functioning
3. Disturbance in 1 and 2 interferes with daily function
4. Does not occur exclusively during delirium
Activities of Daily Living
ADLs: bathing, toileting, transfer, dressing, eating
IADLs (executive functioning):– Maintaining household– Shopping– Transportation– Finances
Diagnosis of Dementia
Delirium: acute, clouding of sensorium, fluctuations in level of consciousness, difficulty with attention and concentration
Depression: more likely to complain of memory loss than in those with dementia
Delirium and depression both markers for future dementia
5% people over age 65 and 35-50 % over 85 have dementia, pretest probability of dementia in older person with memory loss at least 60%
Alzheimer’s Disease
60-80% of cases of dementia in older patients Memory loss, personality changes, global cognitive
dysfunction and functional impairments Visual spatial disturbances (early finding) Apraxia Language disturbances Personality changes Delusions/hallucinations (usually later in course)
Alzheimer’s Disease
Depression occurs in 1/3 Delusions and hallucinations in 1/3 Extracellular deposition of amyloid-beta
protein, intracellular neurofibrillary tangles, and loss of neurons
Diagnosis at autopsy
Alzheimer’s Disease
Onset usually near age 65; older age, more likely diagnosis
Absence of focal neurological signs (but significant overlap in the elderly with hx of CVAs…)
Aphasia, apraxia, agnosia Family hx Normal/nonspecific EEG Personality changes
Vascular dementia
Onset of cognitive deficits associated with a stroke (but often no clear hx of CVA, more multiple small, undiagnosed CVAs)
Abrupt onset of sxs with stepwise deterioration Findings on neurological examination Infarcts on cerebral imaging (do not over read ct and
mri scans….) In reality, significant overlap between alzheimer’s and
vascular dementias; 90 y/o likely to have both based purely on demographics; treatment likely targets both…
Dementia with Parkinson’s
30% with PD may develop dementia; Risk Factors:– Age over 70– Depression– Confusion/psychosis on levodopa– Facial masking upon presentation
Hallucinations and delusions– May be exacerbated by treatment
Dementia with Lewy Bodies
Cortical Lewy Bodies on path Overlap with AD and PD Fluctuations in mental status (may appear delirious) Early delusions and hallucinations Mild extrapyramidal signs Neuroleptic hypersensitivity!!! Unexplained falls or transient changes in
consciousness
Progressive Supranuclear Palsy
Uncommon Vertical supranuclear palsy with downward
gaze abnormalities Postural instability Falls (especially with stairs) “surprised look” Difficulty with spilling food/drink
Frontal Lobe Dementia
Impairment of executive function– Initiation– Goal setting– planning
Disinhibited behavior Cognitive testing may be normal/minimally abnormal;
memory loss not prominent early feature 5-10% cases of dementia Onset usually 45-65
Frontal Lobe Dementia…
Focal atrophy of frontal and/or anterior temporal lobes
Frontal lobe degeneration of the non-AD type (lack of distinctive histopath findings seen with AD or Pick’s)
May be autosomal dominant (inherited form known as frontotemporal dementia)
Pick’s Disease
Subtype of frontal lobe dementia Pick bodies (silver staining intracytoplasmic
inclusions in neocortex and hippocampus) Language abnormalities
– Logorrhea (abundant unfocused speech)– Echolalia (spontaneous repetition of
words/phrases)– Palilalia (compulsive repetition of phrases)
Primary Progressive Aphasia
Patients slowly develop nonfluent, anomic aphasia with hesitant, effortful speech
Repetition, reading, writing also impaired; comprehension initially preserved
Slow progression, initially memory preserved but 75% eventually develop nonlanguage deficits; most patients eventually become mute
Average age of onset 60
“Reversible” Causes of Dementia
?10% of all patients with dementia; in reality, only 2-3% at most will truly have a reversible cause of dementia
“Modifiable” Causes of Dementia
Medications Alcohol Metabolic (b12, thyroid, hyponatremia,
hypercalcemia, hepatic and renal dysfunction)
Depression? (likely marker though…) CNS neoplasms, chronic subdural NPH
Normal Pressure Hydrocephalus
Triad:– Gait disturbance– Urinary incontinence– Cognitive dysfunction
NPH
Diagnosis: initially on neuroimaging Miller Fisher test: objective gait assessment
before and after removal of 30 cc CSF Radioisotope diffusion studies of CSF
Creutzfeldt-Jacob Disease
Rapid onset and deterioration Motor deficits Seizures Slowing and periodic complexes on EEG Myotonic activity
Other infections and dementia
Syphilis HIV
MMSE
24/30 suggestive of dementia (sens 87%, spec 82%)
Not sensitive for MCI Spuriously low in people with low educational
level, low SES, poor language skills, illiteracy, impaired vision
Not sensitive in people with higher educational background
Additional evaluation
Clockface Short assessments with good validity: 3 item recall
and clockface Neurological exam (focality, frontal release signs
such as grasp, jawjerk; apraxia, cogwheeling, eye movements)
Lab testing and neuroimaging Apolipoprotein E epsilon 4 allele: probably not
Prognosis
Previous estimate of median survival after onset of dementia have ranged from 5-10 years
Length bias: failing to consider people with rapidly progressive illness who died before they could be included in the study
Prognosis…
NEJM, april 2001 Data from Canadian Study of Health and
Aging, estimate adjusted for length bias, with random sample of 10,263 people over age 65 screened for cognitive impairment; for those with dementia, ascertained date of onset and conducted followup for 5 years
Prognosis…
821 subjects (396 with probably AD) Unadjusted median survival 3.3 years Median survival 3.1 years for those with
probable AD
Treatment of AD…
Tacrine
Cholinesterase inhibitor 1 systematic review with 5 RCTs, 1434 people, 1-39
weeks No difference in overall clinical improvement Some clinically insignificant improvement in cognition Significant risk of LFT abnormalities: NO ON USE
Donepezil
Aricept Cholinesterse inhibitor Easy titration (start 5/day, then 10) Side effects: GI (nausea, diarrhea) Associated with improved cognitive function;
main effect seems to be lessening of rate of decline, delayed time to needing nursing home/more intensive care
Other agents…
Rivastigmine Galantamine Cholinesterase inhibitors ?more side effects, more titration required Future directions:
– Prevention of delirium in at risk patients (cholinergic theory of delirium)
– Behavioral effects in those with severe dementia– Treatment of Lewy Body dementia– Treatment of mixed Vascular/AD dementia
Comments about cholinesterase inhibitor studies…
Highly selected patients (mild-mod dementia) ?QOL improvements… Not known: severe dementia and mild CI
Memantine
NEJM april 2003 Moderate to severe AD (MMSE 3-14) N-methyl D aspartate (NMDA) receptor antagonist;
theory that overstimulation of NMDA receptor be glutamate leads to progressive damage in neurodegenerative diseases
28 week, double blinded, placebo controlled study; 126 in each group; 67% female, mean age 76, mean MMSE 7.9
Memantine…
Found less decline in ADL scores, less decline in MMSE (-.5 instead of –1.2)
Problem: significant drop outs (overall 28% dropout rate) in both groups; data analyzed did not account for drop outs, followed those “at risk”
Selegiline
Unclear benefit Less than 10mg day, selective MAO B
inhibitor Small studies, not very conclusive
Vitamin E (alpha tocopherol)
NEJM 1997: selegiline, vit E, both , placebo for tx of AD
Double blind, placebo controlled, RCT with mod AD; 341 patients
Primary outcome: time to death, institutionalization, loss of ADLS, severe dementia
Baseline MMSE higher in placebo group No difference in outcomes; adjusted for MMSE
differences at baseline and found delay in time to NH from 670 days with vit E to 440 days with placebo)
Ginkgo Biloba
1 systematic review of 9 double blind RCTs with AD, vascular, or mixed dementia
Heterogeneity, short durations High withdrawal rates; best studies have
shown no sig change in clinician’s global impression scores
Other treatments
NO good evidence to support estrogens or NSAIDS
Other treatments…
Behavioural/agitation:– Nonpharm strategies– Low dose newer antipsychotics (.5 risperidone, olanzepine);
Olanzepine has higher anticholinergic profile, but may benefit/not worsen tremor/rigidity of Parkinson’s
– Reasons for NH placement: Agitation Incontinence Falls Caregiver stress
MMSE tips…
No on serial sevens (months backwards, name backwards… assessment of attention)
Assess literacy prior Assess for dominant hand prior to handing paper
over Do not over lead… 3 item repetition, repeat all 3 then have patients
repeat; 3 stage command, repeat all 3 parts of command and then have patient do…