Dementia with Parkinson Disease and Dementia with Gait Disturbance

Educational Objectives

The goal of this program is to improve the management of neurocognitive disorders. After hearing and assimilating this program, the clinician will be better able to:

1. Assess patients with dementia for psychotic symptoms.

2. Differentiate among psychotic syndromes observed in patients with dementia.

3. Recognize the risks of antipsychotic therapy in elderly patients with dementia.

4. Differentiate Parkinson disease from other parkinsonian disorders.

5. Diagnose and treat individual parkinsonism syndromes.

Summary

Background: ioflupane (DaTSCAN) imaging can detect presence of parkinsonism but may fail to differentiate Parkinson Disease (PD) from other parkinsonian syndromes; parkinsonism — bradykinesia as assessed by Unified Parkinson’s Disease Rating Scale (UPDRS; tests repetitive fine-motor movements); slowness or decremental amplitude of movement considered diagnostic; underlying features differentiate individual parkinsonian disorders

Parkinson disease: features — bradykinesia plus resting tremor; rigidity (greater in limbs than in axial spine [neck]); postural instability develops after ≈8 yr; good response to levodopa-carbidopa therapy differentiates PD from most other parkinsonian disorders; second most common neurodegenerative disorder (occurs in 1% of population >60 yr of age); diagnosis clinical, based on motor features; cognitive deficits subtle early in disease; risk for mild cognitive impairments (CI) twice that in general population; bradyphrenia and decreased verbal fluency most common CIs in early PD; 10% of patients develop dementia within 3.5 yr of symptom onset; early decrease in verbal fluency predicts dementia; 15 yr after onset of motor symptoms, 84% of patients have cognitive decline and 48% have dementia; diagnosis of probable PD — bradykinesia; ≥1 of rigidity, resting tremor of 4 to 6 Hz, or postural instability not attributable to other conditions; exclude other causes of parkinsonism; excellent response (70%-100%) to levodopa persists for ≥5 yr; clinical course ≥10 yr

Atypical parkinsonism: differences from PD — falls at presentation and early in course of disease; poor response to levodopa; symmetry at onset of disease; rapid progression (Hoehn and Yahr stage III [wheelchair-bound within 3 yr]); tremor uncommon; dysautonomia usually indicates multiple system atrophy (MSA)

Dementia with Lewy bodies (DLB): features — symmetric; dementia typically precedes, or occurs ≤1 yr after onset of motor symptoms; visual hallucinations; fluctuating levels of cognition; poor response to levodopa; dementia — prominent or persistent memory impairment, usually becoming more evident with disease progression; deficits in attention, frontal subcortical, and visuospatial skills; diagnosis — 2 features necessary for probable, 1 for possible disease; fluctuating cognition, with markedly variable attention and alertness; recurrent well-formed and detailed visual hallucinations; spontaneous features of parkinsonism; specific to DLB — neuroleptic sensitivity, systematized delusions, and nonvisual hallucinations; similarities to PD — cognitive profile; fluctuation in cognition; extrapyramidal features; neuropsychiatric symptoms; distribution and severity of Lewy bodies; cholinergic and dopaminergic deficits; neuroleptic sensitivity (less common in PD); response to cholinesterase inhibitors (eg, rivastigmine); feature that distinguishes PD from DLB — motor symptoms in PD precede dementia by ≥1 yr

Progressive supranuclear palsy (PSP): features — slowing of vertical saccades or vertical supranuclear gaze palsy; postural instability, with falls within 1 yr of symptom onset; rigidity (greater axially than in limbs); poor response to levodopa; procerus sign (worried or astonished blank stare); most common clinical presentation unexplained falling backwards without loss of consciousness; postural instability — occurs average of 17 mo after onset of symptoms (average of 3 mo in corticobasal degeneration [CBD], 54 mo in DLB, and 8 yr in PD); common symptoms — motor symptoms seen in all patients; cognitive behavioral in 89%; systemic and bulbar in 80%; sleep disturbance in 60%; early frontal lobe CI seen in 10%; most disturbances in abstract thought, executive function, verbal fluency, and behavior; cognitive study — 57% of patients with PSP had CI per Dementia Rating Scale (DRS); 40% impaired in one cognitive domain, 40% impaired in multiple domains

Diagnosis: definite PSP — pathologic diagnosis; probable PSP — gradually progressive disorder with onset after 40 yr of age; vertical supranuclear gaze palsy and postural instability with tendency to fall within 1 yr of onset; no evidence of other disease that would explain symptoms; imaging — shows atrophy of midbrain tegmentum (hummingbird sign); anteroposterior (AP) diameter ≤13.4 mm strong indicator of PSP; sagittal magnetic resonance imaging (MRI) helpful in diagnosis

Corticobasal syndrome (CBS): features — marked asymmetry; limb rigidity; akinesia; dystonia or myoclonus; orobuccal or limb apraxia; corticosensory deficits; alien limb phenomena; poor response to levodopa; CBS and PSP syndrome 2 of 4 phenotypes of CBD; PSP and CBD 4-repeat tauopathies with considerable overlap in distribution of tau proteins and phenotypic spectrum; CBD rare before 50 yr of age (mean age of onset ≈60 yr); cognitive, language, or behavioral changes usually develop before onset of motor symptoms; may be misdiagnosed as AD or frontotemporal dementia until ≈3 yr after onset of symptoms (time of motor symptom presentation); unilateral limb apraxia prominent, with inability to perform gross or fine motor movements (brain no longer able to communicate with affected limb); cortical function study — 52% of patients have CI at 3 yr, 70% over course of disease; 46% have behavioral changes at presentation, 56% over course of disease; motor findings — include limb rigidity (most common; levitation may be seen), postural instability, axial rigidity, tremor (less frequently), and limb dystonia; physical examination — asymmetry, initially of upper limb; apraxia, usually ideational; ideomotor apraxia seen later in disease; corticosensory loss seen as agraphesthesia, astereognosis, or extinction; minimal to absent movement of involved arm during walking; focal myoclonus

Multiple system atrophy: features — autonomic failure early in course of disease; episodic resting tremor; rigidity (greater in limbs than axially); postural instability; cerebellar syndrome leading to gait and limb ataxia; poor response to levodopa; phenotypes include MSA parkinsonism (MSAP) and MSA cerebellar (MSAC); mean age of onset 54 to 60 yr; bladder or erectile dysfunction often initial signs; MSAC unlikely if patient has dementia; cognitive dysfunction in MSAP similar to that of PD but less common or severe; cognitive study — deficits in visuospatial and constructional function, verbal fluency, and executive function seen in MSAP; only deficits of visuospatial and constructional function seen in MSAC; probable and possible MSA — patients >30 yr of age; autonomic dysfunction key feature; orthostatic hypotension (defined as decrease of 30/15 mm/Hg after 3 min of standing); poor response to levodopa, or cerebellar syndrome (gait and limb ataxia, dysarthria, hypometric saccades); MRI features supporting diagnosis — include olivopontocerebellar atrophy and atrophy of putamen; differential diagnosis — includes adult-onset cerebellar ataxias

Vascular parkinsonism (VP): features — poor response (20%-38%) to levodopa, narrow-based magnetic gait, and abnormal reflexes (eg, snout, palmomental) help to differentiate VP from idiopathic PD; patients more prone to postural instability, falls, and dementia; pseudobulbar palsy and urinary incontinence more likely than in PD; postural tremor more common because of thalamic involvement; pyramidal signs found in 63% of patients with VP (vs 0% in PD); neuroimaging — 90% to 100% of patients have abnormalities on computed tomography or MRI but no specific abnormal structural imaging pattern; abnormalities include multiple-territory infarcts, periventricular and subcortical white matter lesions, and ischemic lesions of basal ganglia; ioflupane imaging studies — reduction in uptake seen in PD but not in VP

Normal-pressure hydrocephalus (NPH): features — wide-based magnetic gait disturbance; urinary incontinence; dementia (usually profound and subcortical); frontal and subcortical deficits (usually earliest cognitive signs) include psychomotor slowing, impaired attention, executive and visuospatial dysfunction; AD pathology seen in 75% of patients with NPH who have significant dementia at time of shunting or surgery; freezing of motion much more frequent in NPH than in PD; disequilibrium and slow gait occur secondary to gait apraxia and decreased stride length; 95% of patients have detrusor overactivity; patients may have features of parkinsonism with low response to levodopa; assessment and treatment — high-volume lumbar puncture (LP) to remove ≥30 mL of cerebral spinal fluid (CSF; alternatively, external ventricular drain may be used but requires 3-day hospitalization); perform evaluation within 6 hr of, and shortly after, LP (before reaccumulation of fluid and return of symptoms); gait assessment includes “sit up and stand” test; timed 10-m walk (most important examination) should show >10% improvement in walking time after LP; imaging — shows enlarged ventricles; maximal width of anterior horns divided by biparietal diameter >0.3 often indicates NPH; rule out significant temporal lobe atrophy (may cause ex vacuo dilatation; bleeding likely if shunted); look for unrelated secondary cause if CSF pressure elevated; removal of 40 to 50 mL of CSF suggests potential benefit of shunting; MRI CSF flow studies have no proven predictive value; NPH study — 83% of patients treated with shunting showed improvement in gait, 65% had improved reaction times, 48% had improvement in memory, and 96% noted subjective improvement; less significant improvement seen after 5 yr, possibly because of underlying AD pathology

Readings

Armstrong MJ et al: Criteria for the diagnosis of corticobasal degeneration. Neurology 2013 Jan 29; 80(5): 496–503; Boeve BF: Progressive supranuclear palsy. Parkinsonism Relat Disord 2012 Jan;18 Suppl 1:S192-4; Brown RG et al: Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy. Brain 2010 Aug;133(Pt 8):2382-93; Kalra S et al: Differentiating vascular parkinsonism from idiopathic Parkinson’s disease: a systematic review. Mov Disord 2010 Jan 30;25(2):149-56; Kawai Y et al: Cognitive impairments in multiple system atrophy: MSA-C vs MSA-P. Neurology 2008 Apr 15;70(16 Pt 2):1390-6; Lippa CF et al: DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology 2007 Mar 13;68(11):812-9; Ludolf AC et al: Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options. Eur J Neurol 2009 Mar;16(3):297-309; Shprecher D et al: Normal Pressure Hydrocephalus: Diagnosis and Treatment. Curr Neurol Neurosci Rep 2008 Sep; 8(5): 371–376.

Disclosures

For this program, members of the faculty and the planning committee reported nothing to disclose.

Acknowledgements

Dr. Bluett was recorded at Breakthroughs in Neuro-Cognitive Disorders, held June 11, 2016, in Las Vegas, NV, and presented by the Cleveland Clinic Lou Ruvo Center for Brain Health. For more information about CME activities from the Cleveland Clinic Lou Ruvo Center for Brain Health, please visit ccfcme.org/DementiaSeries. The Audio Digest Foundation thanks the speakers and the Cleveland Clinic Lou Ruvo Center for Brain Health for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

NE072002

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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