Cortical Dementia

Alzheimer Disease¶

o MCC of dementia (65-80%), women more likely to get  Most cases are not familial, but polygenic factors increase risk  Increased incidence in Trisomy 21, Downs  Cognitive > Psychiatric o Symptoms  Insidious Onset • Gradual development of forgetfulness • Subacute decline • Typically diagnosed w/new behavioral problems and forgetting facts the patient previously remembered  Early, insidious short-term memory loss • Early: General impairment in new memory formation and higher executive function. Decreased MMSE • Impairment in episodic memory (amnesia) • Language deficits and spatial disorientation • Frank dementia, aphasia, agnosia • Cannot encode new information, even with cues • Dysnomia (forgetting words) • Aphasia (diminished ability to produce language and spontaneous speech), apraxia (Inability to perform previously learned motor tasks), and agnosia (inability to recognize objects, persons, sounds, and shapes) o Cognitive decline characteristic of cerebral cortex  Echolalia (dramatic repetition of every spoken phrase)  Later, Personality changes  Lack gait abnormalities and urinary incontinence • Cortical rather than subcortical processing dysfunction o Diagnosis:  MoCA 16-17 (97% sensitive)  MRI: Gross atrophy in the mesotemporal lobe, as well as white matter lesions • Early: Mesial temporal lobe (hippocampus) is the first area affected o Diffuse Atrophy and sulci flattening, Ventricular Enlargement (third and lateral ventricles) • Loss of cholinergic neurons in basal forebrain, Degeneration of cholinergic neurons and degeneration in the hippocampus and cortex • Primarily parietal-occipital (non-amnestic form) • Decreased Ach activity, reduced brain choline acetyltransferase • NMDA overstimulation by glutamate leading to calcium influx and excitotoxicity  FDG PET Scan: F-Fluorodeoxyglucose (FDG) used to detect amyloid plaques • May differentiated frontotemporal from Alzheimer disease • Get after MRI if needed • FDA approved, not covered by insurance  Biopsy: Amyloid plaques deposited around the neuron and neurofibrillary tangles deposited inside the neuron • Beta amyloid plaques and Neurofibrillary tangles o Tangles are protein aggregates in neurons from tau hyperphosphorylation (correlate with disease severity best) • Neuritic plaques that stain silver, PAS (+) o Treatment  Memory • 1) Acetylcholinesterase inhibitors (centrally acting) o Tacrine o Donepezil (Aricept)  Relative CI: SSS, LBBB, Uncontrolled Asthma, Angle-closure Glaucoma, Ulcer Disease (A SLUG) o Rivastigmine (Exelon), patch available o Galantamine (Razadyne)  GI upset and bradycardia, orthostasis, N/V • ± NMDA antagonist (moderate/severe) o Memantine (Namenda)  Blocks glutamate induced excitotoxicity, slowing the decline  Combination better than CI alone • Escalate doses every 4-6 weeks to minimize SEs  Agitation • 1) Nonpharmacologic Interventions o https://pubmed.ncbi.nlm.nih.gov/23168825/ o https://pubmed.ncbi.nlm.nih.gov/25452601/ o Behavioral and Environmental Therapy • Safety Risk or No response to Nonpharmacologic o Low-dose Antipsychotics o Antipsychotics increase mortality  SSRIs, Trazadone may help

Frontotemporal Dementia (FTD)¶

 AD inheritance in 20-40% o Symptoms  Early onset <65 y/o usually (50s-60s), males > females  Early Personality changes • Disinhibition > memory loss in early disease • Apathy, disinhibition, and compulsive behavior • Hoarding, hyperorality  Tendency toward concrete thinking  Progresses more rapidly, more significant personality and behavioral  Absence of insight into their condition o Frontotemporal atrophy  Spherical silver staining tau aggregates in neurons • Associated with TDP-43 and FUS  Primarily affecting bilateral frontal and anterior temporal lobes o 3 Subtypes:  Behavioral Variant (bvFTD), Pick’s Disease • Atrophy of Frontal>Temporal Lobes • Accumulation of tau protein inclusions in hippocampi, temporal lobes and frontal lobes • Psychiatric > cognitive ± motor • Compulsions, impulsions, gluttony  Semantic Dementia (SD) • Primarily Dominant Temporal volume loss • Word Finding Difficulty  Primary Progressive Non-Fluent Aphasia (PPA) • Primarily Dominant Temporal volume loss • Impaired Speech fluency with slower speech o All 3 subtypes lead to a combination dementia with:  Personality changes, disinhibition, apathy, impaired social judgement • Dominant Frontal Lobe  Verbal fluency problems  Word-finding difficulty • Dominant Temporal Lobe o Treatment  No good treatment • Increased risk of mortality of meds aimed at symptoms below  SSRIs or trazodone for neuropsychic symptoms • Paroxetine 10mg daily to BID or Trazodone 25mg daily (Grade 2C)  Atypical Antipsychotics last resort (High risk for EPS) • Quetiapine (12.5-25mg)