ANNA BORISOVSKAYA, MD (WITH CONTRIBUTIONS BY

J. FREDERICK, MD AND S. THIELKE, MD)

DEMENTIA: EVALUATION AND TREATMENT

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Epidemiology

US population is “graying”By 2030 there may be 70 million elderly in

the US (currently around 35 million)Prevalence of dementia in 65+ year olds: 6-

8%Prevalence of dementia in 80+ year olds:

30%Most common type of dementia is

Alzheimer’s: 5.2 million Americans have Alzheimer’s as of 2013

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Terminology

Deriving from Latin (demens – mad)“A mental illness that causes someone to be

unable to think clearly or to understand what is real and what is not real” – according to Merriam-Webster dictionary

In psychiatry, used to be termed dementia, now called major neurocognitive disorder

“Early onset” – before the age of 60, often familial, more common for FTD

“Late onset” – after the age of 60

DSM-V Criteria for Major Neurocognitive Disorder

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A. Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains*:

- Learning and memory-Complex attention- Language -Perceptual-motor- Executive function -Social cognitionB. The cognitive deficits interfere with independence in everyday activities. At a minimum, assistance should be required with complex instrumental activities of daily living, such as paying bills or managing medicationsC. The cognitive deficits don’t occur exclusively in the context of a deliriumD. The cognitive deficits aren’t better explained by another mental disorder* Evidence of decline is based on: concern of the individual, a knowledgeable informant, or the clinician that there has been a significant decline in cognitive function and a substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing or in its absence another quantified clinical assessment.

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Common syndromes encountered in dementia

Aphasia – problems with language, comprehensionApraxia – problems with carrying out motor

activities (that the person was previously able to do)Agnosia – inability to recognize objects despite

intact sensory function (visual or tactile)Impaired executive function: difficulty with

planning, initiating, sequencing, monitoring, or stopping complex behaviors

All of the above contribute to loss of IADLsCognitive decline AND associated neuropsychiatric symptoms lead to increasing dependence on others and often eventual institutionalization

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ADL and IADL

Activities of daily living (ADL)BathingDressingGroomingToiletingContinenceTransferring

Instrumental activities of daily living (IADL)Using a phoneTravelShoppingPreparing mealsHouseworkMedication

managementMoney management

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Someone presents with cognitive problems… what do you do?

Thorough history (medical, psychiatric, neurological)

Speak to the collateral!! Are ADL/IADLs affected?Physical and neurological examCognitive testing (screening, then more detailed if

needed)Labs and imaging (rule out reversible causes)Consider neuropsychological testing or referral to

psychiatry or neurologyDetermine the etiology/establish the diagnosisTreat! (or refer)

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Labwork/Imaging

LabworkChem 10CBCLFTsTSHB12, FolateRPR, HIVOthers only if clinical

suspicion is high

ImagingCT HEAD

NONCONTRAST is standard

MRI if vascular dementia is suspected

SPECT or PET – usually not in the initial workup, but may be helpful to aid in difficult diagnosis, r/o FTD

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A few words about “reversible” dementias

Drug toxicityMetabolic disturbanceNormal pressure hydrocephalusMass lesion (tumor, subdural hematoma)Infection (meningitis, syphilis)Collagen-Vascular disease (SLE, Sacroid)Endocrine disorder (thyroid, parathyroid)Nutritional disease (B12, thiamine, folate)Other (COPD, CHF, Liver disease, apnea…)

Only 9% are potentially reversibleOnly 0.6% actually reverse with treatment

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Cognitive screening

MMSE (beware of false positives and negatives)- useful to have at baseline, can track changes over time. In Alzheimer’s, patients lose 3 points/year.

MOCA – free, comprehensive, not easy! Catches those with higher premorbid functioning levels. Mocatest.org

Mini-Cog – combines clock drawing and three item memory test. See scoring guidelines next slide.

SLUMS – better psychometric properties than MMSE, with scoring normed to educational level http://medschool.slu.edu/agingsuccessfully/pdfsurveys/slumsexam_05.pdf

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MINI-COG

Your best bet in a busy clinic setting. 1. Instruct the patient to listen carefully to and remember

these 3 words: banana-sunrise-chair2. Instruct the patient to draw the face of a clock, after the

numbers are placed, ask them to draw the hands of the clock to read “one ten.”

3. Ask the patient to repeat the 3 previously stated words.SCORING: 1 point for each recalled word. Patients recalling none of the words are cognitively impaired (score 0). Patients recalling all 3 words are not cognitively impaired (Score 3). Patients with word recall or 1-2 words are classified based on the clock drawing test: abnormal clock= cognitively impaired, normal = not cognitively impaired.

Clock Drawing Test--abnormal

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Dementia syndromes

Alzheimer’s diseaseVascular dementiaLewy body dementia (LBD)Parkinson’s disease dementia (PDD)Fronto-temporal dementia (FTD)Mixed pathologyKorsakoff’s

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Alzheimer’s disease

Insidious onset, gradual progression, incidence age-relatedShort term memory problems on presentationMost common dementing illnessUltimate diagnosis based on pathology of neurofibrillary

tangles and senile plaques Biochemically characterized by a deficiency of acetylcholine,

with cortex, amygdala, hippocampus all affectedBasal nucleus of Meynert depleted of acetylcholine-containing

neuronsIn minority of cases there’s an autosomal dominant inheritance

linked to chromosomes 1, 14, or 21 (early onset)Apolipoprotein E gene, coded on chromosome 19, when

homozygous for allele E4, increases the risk for late onset Alzheimer’s

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Course of Alzheimer’s Disease

Mild (MMSE 20-24) – primarily memory and visuospatial deficits, mild executive functioning impairmentModerate (MMSE 11-20) – more pronounced aphasia, apraxia, loss of IADLs, may need increased assistance with ADLs, often exhibiting neuropsychiatric symptomsSevere (MMSE 0-10) – severe language disturbances, pronounced neuropsych manifestations, neurological symptoms (rigidity, incontinence, dysphagia, gait disturbance)Death 8-12 years after the diagnosisInstitutionalization common with increasing neuropsychiatric sx, loss of ADLs, caregiver stress

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Vascular dementia

10-20% of dementia cases in North America (10-15% cases of AD are actually mixed AD/vascular) NINDS-AIREN criteria used clinically, defined as presence of - Dementia- Cerebrovascular disease (focal signs on neuro exam and

evidence of CVD on imaging)- Relationship between the two, as in:a)Onset of dementia within 3 months since a recognized stroke and/orb)Abrupt deterioration in cognitive function or stepwise, fluctuating progression of cognitive deficits

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Vascular dementia: cortical subtype

Symptoms are related to the areas affected/strategically placed infarcts:Medial frontal: executive dysfunction, abulia,

or apathy. Bilateral medial frontal lobe infarction may cause akinetic mutism.

Left parietal: aphasia, apraxia, or agnosia.Right parietal: hemineglect (anosognosia,

asomatognosia), confusion, agitation, visuospatial and constructional difficulty.

Medial temporal: anterograde amnesia.

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Vascular dementia: subcortical subtype

Lacunar infarcts and chronic ischemia affect white matter pathways and deep cerebral nuclei:Focal motor signsEarly presence of gait disturbance History of unsteadiness and frequent, unprovoked fallsEarly urinary frequency, urgency, and other urinary

symptoms not explained by urologic diseasePseudobulbar palsyPersonality and mood changes, abulia, apathy,

depression, emotional incontinenceCognitive disorder characterized by relatively mild

memory deficit, psychomotor retardation, and abnormal executive function

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Dementia with Lewy Bodies

4-33% of dementia cases are LBD (when autopsy is performed, greater frequency is found)

Cortical Lewy bodies are the hallmarkTough to diagnose, especially in mixed casesDiagnosis paramount due to particular treatment considerations!

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Diagnosis of LBD

DementiaPresence of fluctuation in cognition/alertness,

Parkinsonism, and visual hallucinationsSuggestive features are REM sleep disorder,

severe sensitivity to neuroleptics, and low dopamine transporter uptake in basal ganglia on SPECT or PET

Falls, syncope, autonomic dysfunction, depression, delusions are common but not diagnostic in and of themselves

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Parkinson’s disease dementia (PDD)

31-41% of patients with Parkinson’s have dementia

Cholinergic dysfunction theorized to be involved in genesis

Characterized by executive dysfunction, visuospatial impairments, verbal memory problems, visual hallucinations

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Frontotemporal dementia

Also known as Pick’s disease though that is just a subtype (or behavioral variant)

Another type is progressive aphasiaUsually of earlier onset (40-60 years of age)Memory impairment not that common at the

onset of the diseaseBrain imaging characterized either by frank

FT atrophy or by decreased metabolism in FT lobes on functional imaging

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“Walnut brain”

Click icon to add picture“Walnut brain”

Notice the profound loss of matter in the frontal lobes, to a slightly lesser degree in the temporal lobes, in comparison with relatively preserved parietal and occipital lobes

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Core diagnostic featuresSupportive diagnostic features

A. Insidious onset and gradual progression

B. Early decline in social interpersonal conduct

C. Early impairment in regulation of personal conduct

D. Early emotional blunting

E. Early loss of insight

A. Behavioral disorder – decline in hygiene, mental rigidity, distractibility, hyperorality, perseverative behavior, utilization behavior

B. Change in speech and language – altered speech output, stereotypy of speech, echolalia, perseveration, mutism

C. Physical signs – primitive reflexes, incontinence, akinesia, rigidity, tremor, low/labile BP

D. Investigations – impairment of frontal lobe neuropsych tests, normal EEG, predominant frontal and/or anterior temporal abnormality on brain imaging

Behavioral variant FTD (BvFTD)

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Treatment

1. Address cognitive dysfunction2. Address neuropsychiatric symptoms3. Address the needs of the caregiver and the

dyad of patient/caregiver4. Consider the environment/living situation

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Treatment: Cognitive dysfunction

Acetylcholinesterase inhibitors (see next slide) – use in all stages of AD, earlier is better (but not in MCI)

Memantine – for moderate to severe stages of the disease

Do not use AchE inhibitors in FTD, do try them in other types of dementia

Consider cognitive interventions (stimulation, rehabilitation, training)

Physical exerciseMediterranean diet has the best evidence

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Treatment: Cognitive Enhancers

Caution: side effects ahead. AchE inhibitors cause bradycardia, diarrhea, nausea. Gradual dose adjustments recommended.

Memantine is relatively free of these side effects.

Adjust doses in renal/hepatic impairment.

Medication Dosing Guidelines NotesDonepezil Initial dose 5 mg at bedtime

Titrate to 10 mg once daily at 4-6 weeksFor moderate to severe dementia, may titrate to 23 mg at 3 months

The only AchE inhibitor FDA approved for treatment of moderate to severe dementia

Galantamine Initial dose 4 mg twice a dayTitrate to 8 mg twice a day at 4 weeksTitrate to 12 mg twice a day at 4 weeks

Extended release capsules to provide once a day dosing are also available.Dosing adjustment recommended in renal and hepatic impairment.

Rivastigmine Initial dose 1.5 mg twice daily for 2 weeksIncrease in increments of 1.5 mg twice daily every 2 weeks if well toleratedMaximum dose 12 mg a day

Dosing adjustment recommended in renal and hepatic impairment.Use caution when treating low body weight patients.The only AchE inhibitor FDA approved for treatment of cognitive impairment in Parkinson’s disease

Rivastigmine patch

Initial dose 4.6 mg/24 hrs topical once daily for 4 weeksTitrate to 9.5 mg/24 hrs topical once dailyFor severe dementia, may titrate to 13.3 mg/24 hrs topical once daily after 4 weeks at prior dose

Dosing adjustment recommended in hepatic but not in renal impairment.Use caution when treating low body weight patients.Dose adjustment may be needed in high body weight patients.

Memantine Initial dose 5 mg daily, at one week increase to 5 mg twice a day, in another week increase to 5 mg in the morning and 10 mg in the evening, and in another week increase to target dose of 10 mg twice a day

FDA approved for use in moderate to severe ADDose adjustment recommended in severe renal and hepatic impairment. 

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Neuropsychiatric symptoms

Agitation Aggression Depression Anxiety Psychosis

These symptoms are distressing and disruptive for the patients and their caregivers. Agitation and aggression are the reasons why patients end up hospitalized/institutionalized. Caregiver support and psychoeducation may prevent such outcomes. There’s evidence to support this finding, and physician reimbursements reflect their attention to this great need!

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Treatment of neuropsychiatric symptoms

Nonpharmacological approaches should be tried first!And even before that, psychiatric/medical causes of

agitation must be ruled outIdentify precipitating/contributing factors to

agitation/anxietyTeach caregivers how to do the same and provide them

with supportAddress the unmet needs of the patientAllow the patient to remain as independent as possible

when helping them with ADLsUse medications when nonpharmacological methods failed, or succeeded only partially, or when high risk/violence exist

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Options for treatment of agitation

Acetylcholinesterase inhibitors and memantine – not great when effect needed urgently

Atypical antipsychotics (not FDA approved, increase risk of mortality – black box warning, modest efficacy)

Antidepressants – citalopram (consider QTc prolongation)

Carbamazepine – evidence not great (consider numerous side effects and drug interactions)

Propranolol, prazosin – very limited evidence base, though promising for prazosin (consider falls)

Benzodiazepines – emergent use only

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Treatment of other neuropsychiatric sx

Antidepressants for depression in dementia are somewhat controversial. There is little evidence for their use in anxiety in dementia.

For severe depression/suicidality, consider hospitalization, consider ECT

Recommend psychotherapy, exercise, pleasurable activities, support groups, memory aids

Minimize changes in caregivers/environmentMusic therapy is gaining strength as evidence based

intervention for treatment of anxietyTreatment of hallucinations/delusions is not always needed –

but when it is, start antipsychotics (atypical) slowly and titrate gradually

Use quetiapine preferentially in LBD and PDD

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Conclusions

It is paramount to diagnose dementia!Earlier treatment preserves functioningCorrect diagnosis prevents poor outcomes – as in

giving haloperidol to patients with DLBAlways obtain collateral from caregivers, and provide

them with education and supportNeuropsych sx are common and are best addressed

with nonpharmacological strategiesUse cognitive enhancing medications whenever

possibleUse medications for agitation/neuropsych sx when

unavoidable