How Alzheimer’s Disease Differs from Frontal Temporal Lobe Dementia (Pick’s Disease) Josepha A. Cheong, MD University of Florida Departments of Psychiatry and Neurology McKnight Brain Institute Institute on Aging This module describes the features of other dementia disorders that may be associated with Alzheimer’ disease (AD)

Review the different kind of dementia [Mild Cognitive Impairment (MCI)] Frontotemporal Lobe Dementia (FTD) Dementia Lewy Body Type (DLB) Vascular Dementia (VaD)

Language, visuospatial skill, executive abilities, and emotion DEMENTIA Clinical syndrome which is acquired and represents a deterioration from previous function in at least 3 of the following functions: Language, visuospatial skill, executive abilities, and emotion

Dementia Type—Total Population Overall, Alzheimer’s disease accounts for just over half of all dementia— significantly more than any other form. About two fifths of all patients are in each of the mild and moderate stages, and the remaining fifth are in the severe stage Distribution of Dementia Types 1% Mild cognitive impairment 22% 13% Dementia with Lewy bodies Vascular Mixed 14% Other 55% Alzheimer’s disease 22% 2% Alzheimer’s—mild Alzheimer’s—moderate 15% Alzheimer’s—severe 11% Source: Icon and Landis, Fall 2000

Mild Cognitive Impairment (MCI) Patients who are memory impaired but are otherwise functioning well and do not meet clinical criteria for dementia are classified as having MCI Symptoms include Memory complaint, preferably with corroboration Objective memory impairment Normal general cognitive function Intact activities of daily living Not demented Patients with MCI should be recognized and monitored for cognitive and functional decline due to their increased risk for subsequent dementia There are currently no recommended treatments for MCI Petersen RC. Neurology. 2001;56:1133-1142. Petersen RC et al. Arch Neurol. 1999;56:303-308.

Frontotemporal Dementia (FTD) FTD is the most common of the neurodegenerative syndromes produced by frontotemporal lobar degeneration, and is less common than AD, VaD, and DLB Perry RJ. Neurology. 2001;56:46-51. Perry RJ. Neurology. 2000;54:2277-2284. Morris JC. Neurology. 2001;57:173-174.

Frontotemporal Dementia (FTD) Clinical features of FTD include decline in personal hygiene and grooming, mental rigidity and inflexibility, distractibility and impersistence, hyperorality and dietary changes, perseverative and stereotyped behavior, and utilization behavior Perry RJ. Neurology. 2001;56:46-51. Perry RJ. Neurology. 2000;54:2277-2284. Morris JC. Neurology. 2001;57:173-174.

Frontotemporal Dementia (FTD) Current treatment options only address symptomatic management, as there is no evidence for the use of AChEIs in this condition Perry RJ. Neurology. 2001;56:46-51. Perry RJ. Neurology. 2000;54:2277-2284. Morris JC. Neurology. 2001;57:173-174.

Dementia With Lewy Bodies (DLB) Presence of dementia, gait/balance disorder, prominent hallucinations and delusions, sensitivity to traditional antipsychotics, and fluctuations in alertness Heyman A et al. Neurology. 1999;52:1839-1844. Ballard CG et al. Dement Geriatr Cogn Disord. 1999;10:104-108. Barber R et al. Neurology. 1999;52:1153-1158.

Vascular Dementia VaD and AD can be difficult to distinguish, due to overlaps in symptomatology, pathophysiology, and comorbidity

Room for improved criteria for these patients Vascular Dementia A number of patients may have AD with concomitant CVD (“mixed” dementia) Room for improved criteria for these patients

Relationship Between VaD and AD Cholinergic dysfunction (central to AD) is seen in VaD Togashi H et al. Neurosci Lett. 1994;166:117-120. Saito H et al. Clin Exp Pharmacol Physiol. 1995;22(suppl 1):S257-S259. Kalaria RN, Ballard C. Alzheimer Dis Assoc Disord. 1999;13(suppl 3):S115-S123. Wallin A et al. Acta Neurol Scand. 1989;80:518-523. Gottfries CG et al. Dementia. 1994;5:163-167. Tohgi H et al. J Neural Transm. 1996;103:1211-1220.

Frontotemporal Dementia aka Pick’s Disease because of the neuropathology of specific inclusion bodies (Pick bodies) in the neurons Atrophy of the frontal and/or temporal lobe Asymmetric atrophy Miller BL, Cummings JL, et al: Neurology 41:1374-1382, 1991

Frontotemporal Dementia Clinical Syndromes Disinhibition with tactlessness and impulsiveness Primary progressive aphasia with nonfluent verbal output and early mutism Semantic aphasia and visual agnosia Miller BL, Cummings JL, et al: Neurology 41:1374-1382, 1991

Frontotemporal Dementia Genetic Considerations 40% are inherited in an autosomal dominant pattern 20% involve a mutation of the Chr 17 Miller BL, Cummings JL, et al: Neurology 41:1374-1382, 1991

Frontotemporal Dementia Clinical Considerations: Usually begins between 50 – 70 yrs of age Very slow onset with prominent change in personality or language Memory, copying, and calculations are spared until mid-late stages of disease – used to differentiate with AD Miller BL, Cummings JL, et al: Neurology 41:1374-1382, 1991

Frontotemporal Dementia Behavioral Changes: Disinhibition Impulsiveness Tactlessness Impaired social judgment Apathy Depression Miller BL, Cummings JL, et al: Neurology 41:1374-1382, 1991

FTD AD Specific atrophy Apraxia – late Marked personality change – early in the disease Memory impairment – late in the disease Little response to ACHase Inhibitors Pick inclusion bodies on pathology AD Diffuse atrophy Apraxia – early Subtle personality changes Memory Impairment – early in the disease Good response to ACHase inhibitors Neurofibrillary plaques and tangles

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