Non-Alzheimer’s Dementias

Scott Morgan MSIIIDecember 2012

DSM-IV Definition of Dementia

• Major impairment of memory and learning as well as one of:• Impairment handling complex tasks• Impairment in reasoning ability• Impairment spatial ability and orientation• Impaired language

• Insidious and progressive onset

• Symptoms interfere with relationships, work performance, and social activities

Recognizing Dementia

• Memory loss rarely reported by patient• Spouse or family member usually reports• Family reported memory loss is a better predictor

• Commonly thought to just be from aging

• Insidious onset often causes a delay in reporting memory loss

• Must be distinguished from delirium and depression

Mental Status Tests

Parkinson Disease Dementia

• Prevalence of dementia in Parkinson Disease (PD) patients is 41%

• Mild cognitive impairment is common in PD• Does not always meet criteria for dementia

• Genetic factors associated with Parkinson Disease Dementia (PDD)• Multiplications of alpha-synuclein gene• Microtubule-associated protein tau (MAPT) H1/H2 and

MAPT H1/H1 genes• Epsilon 2 and epsilon 4 alleles of the apolipoprotein

gene

Early Clinical Features of PDD

• Executive dysfunction with deficiencies in:• Set shifting• Attention• Planning

• Visuospatial impairment• Facial recognition problems• Impaired tone contrast

• Verbal memory• Difficulty remembering words• Unable to explain their problems

Late Clinical Features of PDD

• Psychosis• Visual hallucinations• Delusions • Spousal infidelity paranoia

• Mood disorders• Depression• Anxiety• Apathy

• Sleep disturbances• Sleep fragmentation• Nightmares• REM sleep behavior disorder• Patient has normal dreams without the muscle

atonia

Treatment of PDD

• Cholinesterase inhibitors• Have a benefit for cognition• No evidence for improvement of neuropsychiatric

symptoms

• For psychosis• Quetiapine• Clozapine

• Avoid anticholinergic medications

Dementia with Lewy Bodies

• Second most common degenerative dementia• 10-22% of all dementia cases

• There have been familial cases, but most are sporadic• Multiplications of alpha-synuclein gene are

associated with familial DLB

• Only known risk factor is increased age• Mean age of onset is 75

• Some studies show more likely in males• Still debated and evidence is not strong

Lewy Body

•Round eosinophilic intranuclear inclusion

•Found in nuclei of neurons of substantia nigra

•Aggregations of alpha-synuclein

•Only detectable by postmortem biopsy

•Do not show up on any scans

Diagnosing DLB

• Features of Alzheimer’s Disease and Parkinson Disease

• More rapid onset than Alzheimer’s

• Can have amyloid plaques similar to Alzheimer’s• Not nearly as numerous as Alzheimer’s

• Different from PDD by• Onset of dementia compared to parkinsonian

symptoms• Before, during, or very shortly after parkinsonian signs

• Can detect brain atrophy with MRI and PET scans• Not necessary for diagnosis but can provide supportive

evidence

Clinical Features of DLB

• Very similar to PDD

• Fluctuating cognition and alertness• Patients can “blank out” or lose consciousness• Episodes last from seconds to days

• Visual hallucinations• Early sign in DLB compared to late in PDD

• Parkinsonism• Gait disorders• Bradykinesia• Limb rigidity

Treatment of DLB

• Treatments are just for symptoms

• No treatment has been found to have disease modifying effects

• Selegiline has been used as a treatment• Limited evidence for effectiveness

Vascular Dementia

• Aka multi-infarct dementia

• Makes up 10-20% of dementia cases

• Risk factors• Very weak evidence to show shared risk factors with

cerebrovascular disease• Some evidence points to metabolic syndrome as a

risk factor• Advanced age is a risk factor for dementia after a

stroke or subclinical infarct

Pathology of VaD

• Large artery infarcts• Usually cortical but sometimes subcortical

• Small artery or lacunar infarcts• Exclusive subcortical in small penetrating arteries• Affect basal ganglia, caudate, thalamus, internal

capsule, cerebellum, and brainstem

• Chronic subcortical ischemia• Small arteries in periventricular white matter• Order of vulnerability – neuron, oligodendrocyte,

myelinated axon, astrocyte, endothelial cell

Diagnosis of VaD

• Neuroimaging• MRI is most sensitive• CT is usually first line scan

• Step-wise loss of cognition and memory• Disease progresses with

each ischemic event• Each progression can be

large or small

Clinical Features of VaD

• Medial frontal• Executive function• Apathy

• Left parietal• Aphasia• Apraxia• Agnosia

• Right parietal• Hemineglect• Confusion• Agitation• Visuopatial difficulty• Constructional difficulty

• Medial temporal• Anterograde amnesia

Specific to area affected

Frontotemporal Dementia

• Aka:• Picks Disease• Pick complex• Frontal lobe dementia

• Age of onset is late 50s to early 60s• Average age is 58

• As the name implies it is a degeneration of the frontal and temporal lobes

Pick Bodies• Build up of tau

proteins in neurons

• Cause neurons to swell and appear spherical

• Silver staining for diagnosis

• Help distinguish from other dementias

Clinical Features of FTD

• Unique because of personality changes• Aggressiveness• New onset of criminal activity• Socially inappropriate• Sexually inappropriate

• Lack of insight

• Progressive non-fluent aphasia• Word-finding difficulty and speech errors

• Unusual eating patterns• Some patients will binge on alcohol

• Incontinence

Diagnosis and Treatment of FTD

• MRI is most common scan used to diagnose

• Very little evidence to support pharmacological treatment• Used to treat symptoms

• Acetylcholinesterase inhibitors used to be used for treatment but falling out of favor

• SSRIs are used to treat depression if this is a symptom

• Neuroleptics can be used but side effects must be weighed against benefits

Summary

• Alzheimer’s dementia is most common dementia

• Memory loss is the major hallmark of dementia

• Dementias are often difficult to diagnose and treat

• Diagnosis is mainly by clinical features rather than using imaging scans

• Most treatments are for symptoms not disease modification

Citation

Hake, Ann Marie et al. Clinical Features and Diagnosis of Dementia with Lewy Bodies. UpToDate.com. Wolters Kluwer Health. October 2012. Accessed: 11/26/12

Hake, Ann Marie et al. Epidemiology, Pathology, and Pathogenesis of Dementia with Lewy Bodies. UpToDate.com. Wolters Kluwer Health. October 2012. Accessed: 11/26/12

Randolph, Christopher. Frontotemporal Dementia: Clinical Features and diagnosis. UpToDate.com. Wolters Kluwer Health. October 2012. Accessed: 11/26/12

Rodnitzky, Robert. Parkinson Disease Dementia. UpToDate.com. Wolters Kluwer Health. October 2012. Accessed: 11/26/12

Shalden, Marie-Florence et al. Evaluation of Cognitive Impairment and Dementia. UpToDate.com. Wolters Kluwer Health. October 2012. Accessed: 11/26/12

Wright, Clinton. Etiology, Clinical Manifestations, and Diagnosis of Vascular Dementia. UpToDate.com. Wolters Kluwer Health. October 2012. Accessed: 11/26/12