Non-Alzheimer’s Dementias Scott Morgan MSIII December 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 For psychosis 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 Specific to area affected Medial frontal Executive function Apathy Left parietal Aphasia Apraxia Agnosia Right parietal Hemineglect Confusion Agitation Visuopatial difficulty Constructional difficulty Medial temporal Anterograde amnesia

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