Neurology & Psychiatry › Dementia & Encephalopathy

Dementia

Notes

Dementia

Sections








Here, we'll address major clinical aspects of dementia.

Overview

Common Etiologies

We'll focus on the leading causes of dementia:

  • Alzheimer's disease (~ 70%), which we can think of it as a disease of progressive short-term memory loss. Although, as we'll see it can cause many different clinical manifestations.
  • Vascular dementia (~15%), which, classically, present with a stepwise cognitive decline.
  • Lewy Body Dementia (~10%), which we can think of it as a combination of dementia and parkinsonism.

Start a table to keep track of key dementia classifications. Will introduce some of them, now, and complete the rest at the end.

Alzheimer's Disease

Gross Pathology

Let's begin with Alzheimer's disease pathology and radiographic features, which will set the stage for our understanding of the key clinical manifestations of the disease.

Temporal & Parietal Lobe Atrophy

We'll start with early areas of atrophy that can be observed on brain imaging.

  • Draw a coronal section and illustrate that there is prominent temporal lobe atrophy.
  • Then, draw an axial section and illustrate prominent parietal lobe atrophy.
    • Generally, the temporal and parietal lobes are affected before the other cerebral lobes. This finding correlates well with some of the key symptoms of Alzheimer's: memory loss and language dysfunction out of the temporal lobes and visuospatial dysfunction due to involvement in the parietal lobe.

Hippocampus Atrophy

  • Now, within the temporal lobe, specify the hippocampus. Show that in Alzheimer's disease, there is severe degeneration of the hippocampal formation. Show a normal hippocampus for comparison.
    • Notably there is degeneration of especially: CA1 (cornu ammonis 1), the entorhinal cortex, and subiculum. As well. there is atrophy of the amygdala and parahippocampal gyrus, which results in dilatation of the temporal horn of the lateral ventricle. Ultimately, as we see, there is gyral shrinkage and sulcal widening as atrophy progresses.

Histopathology

Amyloid Plaques & Neurofibrillary tangles

We provide an in-depth review of the working understanding of the pathophysiology of amyloid and tau in Alzheimer's disease in the advanced topics tutorial. Here, simply indicate a few key histopathological findings:

Amyloid beta plaques

Amyloid beta plaques (senile plaques), which are extracellular aggregates of fibrillar amyloid beta peptide. The term senile plaque stems from the notion that these plaques were observed in autopsies of elderly patients with dementia. * Importantly, they stain red with Congo red staining – the classic amyloid stain – they are found both extracellularly and also in blood vessel walls, as we'll discuss further later. The major cleavage products of amyloid plaques include amyloid-beta 42 and amyloid-beta 40.

Tau neurofibrillary tangles

Tau neurofibrillary tangles, which comprise intracellular conglomerations of hyperphosphorylated tau (a microtubule stabilizing protein); they are the cornerstone to a great deal of neurodegenerative diseases.

  • Tau is a microtubule-stabilizing protein. Hyperphosphorylation of tau weakens the affinity of tau for microtubules, so detached tau proteins aggregate, and form paired helical filaments that conglomerate as densely compacted neurofibrillary tangles. They are insoluble aggregates that crowd the neuronal cell body and extend into the apical dendrite.
  • On histopathology, the neurofibrillary tangles have an ill-defined basophilic appearance on H&E but silver impregnation stains (eg, the modified Bielschowsky stain) and immunohistochemistry making it easier to visualize them.

Hirano bodies

Show a Hirano body, as an intracellular eosinophilic rod (or almond) shaped structure that comprises a lattice of multi-layered actin filaments and actin-binding proteins; they reside within the CA1 sector, most notably.

Clinical-Pathological Symptom Patterns

Now, let's introduce some clinical-pathologic correlations in Alzheimer's disease as a helpful, albeit oversimplifying, way to remember key disease patterns.

Early Alzheimer's Disease

The following are all symptoms that are common to the early stages of Alzheimer's disease:

  • Short-term memory dysfunction occurs from hippocampal degeneration.
  • Word-finding and naming issues arise from temporal lobe degradation (the temporal lobe is essential for language processing and production).
  • Task-sequencing and visuospatial disturbances from parietal lobe degeneration that can produce significant apraxias.

Later Alzheimer's Disease

As degeneration worsens and other areas of the brain are affected, the following symptoms occur (note that they likely have diffuse originations):

  • Remote memory degenerates: remote memory involves storage and retrieval throughout the brain.
  • Neuropsychiatric symptoms become prominent. Apathy, depression, and emotional irritability tend to occur first, followed by personality changes and hallucinations in later stages.
  • Visuospatial dysfunction becomes common and prominent. It manifests with spatial disorientation (eg, trouble staying in a lane when driving, finding a parked car, getting lost (wandering)).

Alzheimer variants

When non-memory symptoms predominate, they may ultimately be categorized as having an Alzheimer variant. Indicate that these variants include:

  • Primary progressive aphasia (logopenic variant), which involves language dysfunction, especially anomia. On exam, patients struggle with verbal fluency tests out-of-proportion to other deficits. Look for temporal lobe degeneration.
  • Frontal variant, which manifests with behavioral dysfunction early-on. Look for frontal lobe degeneration more so than parietal lobe involvement.
  • Posterior cortical atrophy, which manifests with visuospatial dysfunction early-on. Look for early, pronounced parietal lobe degeneration.

Note that primary progressive aphasia and behavioral dysfunction are key phenotypes of frontotemporal dementia (which we discuss elsewhere), as well.

Genetics

Finally, let's address some of the best-known genetic factors in Alzheimer's disease.

Apolipoprotein E (APOE)

Indicate that the best-established genetic risk factor in Alzheimer's involves the Apolipoprotein E (APOE) gene.

  • Specifically indicate that the APOE*E4 allele INCREASES the risk of Alzheimer's.
    • One mutation increases the Alzheimer's risk ~ 3-fold.
    • Two mutations will increase the Alzheimer's risk ~ 10-fold.
  • Whereas, the APOE*E2 allele DECREASES the risk.

Autosomal Dominant, Early-Onset Alzheimer's Disease

Next, let's list three key mutations linked to autosomal dominant early-onset Alzheimer's disease (onset younger than 65 years-old), all of which increase amyloid production.

  • Amyloid Precursor Protein (APP) mutation
  • Presenilin 1 (PSEN1) mutation
  • Presenilin 2 (PSEN2) mutation

Trisomy 21

Finally, indicate that in trisomy 21, there is APP gene triplication (there are 3 copies of the APP gene), which increases the risk of early-onset Alzheimer's disease.

Biomarkers

The core AD CSF biomarkers include total tau (T-tau), phosphorylated tau (P-tau) and the 42 amino acid isoform (Ab42) of b-amyloid as well as Amyloid-PET (18F-flutemetamol amyloid PET) detects amyloid load (burden).

FDG-PET (18F-2-fluoro-2-deoxy-D-glucose PET) detects hypometabolism and is also used but is not considered a core biomarker because it is less specific than Amyloid-PET. Amyloid-PET is particularly helpful in distinguishing AD from frontotemporal dementia (FTD) or multi-infarct dementia but, unfortunately, amyloid plaques are found in normal individuals so it struggles to distinguish AD from normal amyloid build-up.

Treatments

Let's address some key aspects of Alzheimer's dementia treatment.

Symptomatic Management

There are two main classes of symptomatic management, both of which produce small but real improvements in cognitive performance.

Cholinesterase Inhibitors

First, indicate Cholinesterase Inhibitors, which increase cholinergic activity. As we might predict, these cholinergic effects, commonly cause GI hypermotility (loose stools or diarrhea). We need to look-out for potential bradycardia or cardiac conduction abnormalities and the risk of COPD or asthma exacerbations.

Cholinesterase Inhibitors

  • Donepezil
  • Rivastigmine
  • Galantamine
  • Note that in a 2001 study, donepezil was shown to definitively impact disease progression.
    • Winblad B, Engedal K, Soininen H, et al. A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology 2001;57:489–495.
  • Recent studies have shown broader class benefit for the cholinesterase inhibitors in the reduction of cognitive decline and mortality. Galantamine, specifically, was shown to reduce progression to severe dementia.
    • Xu, Hong, Sara Garcia-Ptacek, Linus Jönsson, Anders Wimo, Peter Nordström, and Maria Eriksdotter. "Long-Term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality." Neurology 96, no. 17 (April 27, 2021): e2220–30. https://doi.org/10.1212/WNL.0000000000011832.

NMDA Antagonist

Next, indicate that memantine is an NMDA antagonist: it reduces glutamate excitotoxicity. Although it was originally designated for only moderate to advanced Alzheimer's disease, in practice it is used at all stages of the disease. Paradoxically, it can induce confusion and hallucinations (both of which are already problematic in patients with dementia).

  • Note that although memantine is commonly described as being neuroprotective, it still has not been shown to actually slow the progression of the disease (making it a symptomatic management (despite this designation of being neuroprotective)).
    • Areosa SA, Sherriff F, McShane R. Memantine for dementia. The Cochrane Database of Systematic Reviews. 2005 Jul(3):CD003154. DOI: 10.1002/14651858.cd003154.pub4. PMID: 16034889.
    • Folch J, Busquets O, Ettcheto M, Sánchez-López E, Castro-Torres RD, Verdaguer E, Garcia ML, Olloquequi J, Casadesús G, Beas-Zarate C, Pelegri C, Vilaplana J, Auladell C, Camins A. Memantine for the Treatment of Dementia: A Review on its Current and Future Applications. J Alzheimers Dis. 2018;62(3):1223-1240. doi: 10.3233/JAD-170672. PMID: 29254093; PMCID: PMC5870028.

Disease Altering Treatments

As far as disease-altering medications are concerned, there have been many advancements in amyloid plaque clearance but as of 2023, there have not been definitive substantive advancements in the ability to medications to slow the progression of the disease.

Vascular Dementia

Now, let's address vascular causes of dementia, which is considered the second most common cause of dementia. The vascular dementia nomenclature is quite confusing and contradictory. Here, we will ignore circumstances wherein repeated large vessel infarcts produce cognitive dysfunction. Instead, we will focus on two key, common causes:

  • Multi-Infarct Dementia, specifically, subcortical vascular dementia (aka small vessel dementia, Binswanger disease)
  • Cerebral Amyloid Angiopathy
    • As an oversimplification it is helpful to think of multi-infarct dementia as being a white matter disease of small, silent ischemic strokes and cerebral amyloid angiopathy as a cortical, gray matter, disease of silent and non-silent hemorrhagic strokes.

Multi-Infarct Dementia (aka subcortical vascular dementia)

Clinical/Radiographic Features

Multi-infarct dementia classically presents with a stepwise decline in cognitive function.

Draw an MRI image and show confluent white matter disease to illustrate the accumulation of microvascular disease, centrally.

Management depends on vascular risk factor modification.

Cerebral Amyloid Angiopathy

Pathogenesis

Cerebral amyloid angiopathy is characterized by dementia in the setting of microhemorrhages and lobar hemorrhages.

  • Draw a blood vessel, show the lumen and from central to peripheral, the intima, media, and adventitia.
  • Show that in cerebral amyloid angiopathy there is pathological invasion of amyloid beta in the walls of cerebral cortical small and medium-sized blood vessels and leptomeningeal arteries. We show amyloid in red because, as we discussed with Alzheimer's disease, it stains with Congo red staining (it is "congophilic").
  • There is an important overlap between amyloid accumulation in Alzheimer's disease and in cerebral amyloid angiopathy, which is beyond the scope of this tutorial.

Microhemorrhages

Amyloid accumulation causes microaneurysm formation, rupture, and bleeding.

  • Since bleeding is the primary pathology, we will use an MRI sequence that highlights blood products (in black); show an axial gradient echo image (specifically, a susceptibility weighted image).
  • Show a stippled appearance of micro-bleeds within the cerebral lobes, peripherally.
  • Note that, as a helpful oversimplification, we can think of amyloid angiopathy as impacting the peripheral portion of the brain and multi-infarct dementia as impacting the central portion (mimicking a white matter disease). This distinction easily breaks down, however, when amyloid accumulates in small caliber vessels found centrally in perivascular spaces in the white matter.

Lobar Hemorrhage

Also, show a large lobar hemorrhage, another important consequence of the amyloid angiopathy.

Clinical Management

It can present with spontaneous lobar intracranial hemorrhage, transient ischemic attacks (or so-called 'amyloid spells'), subarachnoid hemorrhage (or cortical superficial siderosis), or without sudden events, simply as a slowly developing dementia.

Management involves reduction of bleeding risk through blood pressure management and the avoidance/reduction of antithrombotic agents (when possible/appropriate).

Lewy Body Dementia

Next, let's address Lewy body dementia, the third most common cause of dementia.
It's helpful to divide LDB into two main categories: Dementia & Parkinsonism.

Dementia

Symptoms

From a dementia standpoint, indicate the following prominent symptoms:

  • Visual hallucinations
  • Delusions. Specifically indicate Capgras syndrome (aka imposter syndrome), in which patients are convinced their spouse (or caretaker) has been replaced by an imposter. We show a familiar face hidden behind an alien mask.
  • Severe fluctuations in level of arousal with sudden sleep attacks.

Parkinsonism

From a parkinsonism standpoint, indicate the following prominent symptoms:

  • Symmetric rigidity, typically without tremor.
  • Gait impairment: show frequent falls to remind ourselves to ask about this important symptom in our interview.
    These symptoms will have a limited response to dopamine (unlike in PD wherein they respond dramatically and are sustained).
  • Also indicate that LDB patients have severe neuroleptic sensitivity, meaning typical antipsychotic medications (eg, haloperidol) will profoundly worsen the parkinsonism and can even lead to neuroleptic malignant syndrome. Atypical antipsychotics are safer but still must be used with caution.
    REM sleep behavior disorder, in which patients act out their dreams, due to dysregulation of muscle atonia during REM sleep.

Histopathology

In terms of the neuropathology, show that cortical Lewy bodies are distinct from brainstem Lewy bodies.

Cortical Lewy Bodies

Show a nucleus within a cortical neuron and then include the Lewy body inclusion, which lack the concentric halo that we'll draw in nigral Lewy bodies: rather, they have a more uniform density. As expected, cortical Lewy bodies stain for alpha-synuclein and ubiquitin via immunohistochemistry.

Nigral Lewy Bodies

Next, draw a cell body from the substantia nigra (the key site of pathology in Parkinson's disease). Show that we recognize it as a nigral dopaminergic cell because of the neuromelanin pigment in the cell body.

Draw a nigral Lewy body, which is indistinguishable from those in Parkinson's disease. Indicate that with alpha-synuclein staining there is a central clearing with a peripheral halo of alpha-synuclein (again, this is not found in cortical Lewy bodies). Show that on H&E staining, the Lewy body has an eosinophilic core with a peripheral halo.

Prognosis

Importantly, the average lifespan for a patient diagnosed with Lewy body dementia is ~ 4 years whereas those diagnosed with Parkinson's disease is ~ 15 years. In addition, as mentioned, dopaminergic agents do not substantially improve parkinsonism symptoms in LDB (whereas they have dramatic impacts on motor symptoms in Parkinson's disease).

Routine Work-up

Before we conclude, let's return to our table to list out some important concepts in the clinical evaluation of dementia.

Brain Imaging

First, indicate that for routine work-up, it is recommended that all individuals suspected of dementia get brain imaging (CT or MRI) to rule-out any reversible causes. Importantly, we should look for subdural hematomas, which can present subacutely in the elderly population and cause prominent cognitive dysfunction.

Laboratory

For routine laboratory work-up, B12 testing and thyroid testing are warranted in all patients. Remember that the blood level of B12 can be spuriously normal if someone is taking B12 supplementation, so we should check methylmalonic acid and homocysteine levels to look for evidence of B12 deficiency, if it is suspected.

Related Diagnoses

Lastly, let's list out some common related diagnoses in dementia. When we see patients in the hospital with cognitive dysfunction, it can be challenging to get a clear history, so it's helpful to know other key causes of cognitive impairment.

Delirium

First, delirium is a common condition in elderly hospitalized patients (occurring in ~ 30% of patients). Delirium manifests with altered alertness, attention, and cognitive processing. Patients have fluctuations in consciousness, inattention, and abnormal thinking potentially with delusions and hallucinations.

Transient global amnesia

Transient global amnesia is a syndrome of transient anterograde amnesia (typically 24 hours in duration). Patients can access remote memories but have a temporary inability to generate new memories.

Wernicke encephalopathy

Wernicke encephalopathy, which is secondary to thiamine (B1) deficiency. It presents with ataxia, delirium, and ophthalmoparesis. Classically, it occurs in patients with alcoholism, but it can occur in other patients with nutritional deficiencies. Wernicke's is a reversible condition but it can transition to Korsakoff syndrome when it becomes chronic and irreversible.

Mild cognitive impairment

Finally, include mild cognitive impairment, which describes a dementia prodrome – patients who have cognitive dysfunction beyond what is expected for normal aging but not yet to the threshold of dementia.

Board Review Questions

Clinical Presentation

Diagnosis

Management

Additional Causes of Dementia

For details regarding additional causes of dementia, please see the Dementia: Advanced Topics tutorial.

References

Apostolova, Liana G. "Alzheimer Disease:" CONTINUUM: Lifelong Learning in Neurology 22, no. 2, Dementia (April 2016): 419–34. https://doi.org/10.1212/CON.0000000000000307.

Areosa, Sastre A, F Sherriff, and R McShane. "Memantine for Dementia." The Cochrane Database of Systematic Reviews, no. 3 (July 1, 2005): CD003154. https://doi.org/10.1002/14651858.cd003154.pub4.

Biffi, Alessandro, and Steven M. Greenberg. "Cerebral Amyloid Angiopathy: A Systematic Review." Journal of Clinical Neurology (Seoul, Korea) 7, no. 1 (March 2011): 1–9. https://doi.org/10.3988/jcn.2011.7.1.1.

Bir, Shyamal C., Muhammad W. Khan, Vijayakumar Javalkar, Eduardo Gonzalez Toledo, and Roger E. Kelley. "Emerging Concepts in Vascular Dementia: A Review." Journal of Stroke and Cerebrovascular Diseases 30, no. 8 (August 1, 2021). https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.105864.

Denes, Gianfranco, and Luigi Pizzamiglio. Handbook of Clinical and Experimental Neuropsychology. Psychology Press, 1999.

Espay, Alberto J., Gustavo A. Da Prat, Alok K. Dwivedi, Federico Rodriguez-Porcel, Jennifer E. Vaughan, Michela Rosso, Johnna L. Devoto, et al. "Deconstructing Normal Pressure Hydrocephalus: Ventriculomegaly as Early Sign of Neurodegeneration." Annals of Neurology 82, no. 4 (October 2017): 503–13. https://doi.org/10.1002/ana.25046.

Finger, Elizabeth C. "Frontotemporal Dementias:" CONTINUUM: Lifelong Learning in Neurology 22, no. 2, Dementia (April 2016): 464–89. https://doi.org/10.1212/CON.0000000000000300.

Folch, Jaume, Oriol Busquets, Miren Ettcheto, Elena Sánchez-López, Ruben Dario Castro-Torres, Ester Verdaguer, Maria Luisa Garcia, et al. "Memantine for the Treatment of Dementia: A Review on Its Current and Future Applications." Journal of Alzheimer's Disease 62, no. 3 (n.d.): 1223–40. https://doi.org/10.3233/JAD-170672.

Geschwind, Michael D. "Rapidly Progressive Dementia:" CONTINUUM: Lifelong Learning in Neurology 22, no. 2, Dementia (April 2016): 510–37. https://doi.org/10.1212/CON.0000000000000319.

Gomperts, Stephen N. "Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia." CONTINUUM: Lifelong Learning in Neurology 22, no. 2, Dementia (April 2016): 435–63. https://doi.org/10.1212/CON.0000000000000309.

Gorno-Tempini, M. L., A. E. Hillis, S. Weintraub, A. Kertesz, M. Mendez, S. F. Cappa, J. M. Ogar, et al. "Classification of Primary Progressive Aphasia and Its Variants." Neurology 76, no. 11 (March 15, 2011): 1006–14. https://doi.org/10.1212/WNL.0b013e31821103e6.

Gouras, Gunnar K., Tomas T. Olsson, and Oskar Hansson. "β-Amyloid Peptides and Amyloid Plaques in Alzheimer's Disease." Neurotherapeutics 12, no. 1 (January 2015): 3–11. https://doi.org/10.1007/s13311-014-0313-y.

Greenberg, Steven M., and Jean-Paul G. Vonsattel. "Diagnosis of Cerebral Amyloid Angiopathy." Stroke 28, no. 7 (July 1997): 1418–22. https://doi.org/10.1161/01.STR.28.7.1418.

Iacono, Diego, Maria Geraci-Erck, Hui Peng, Marcie L. Rabin, and Roger Kurlan. "Reduced Number of Pigmented Neurons in the Substantia Nigra of Dystonia Patients? Findings from Extensive Neuropathologic, Immunohistochemistry, and Quantitative Analyses." Tremor and Other Hyperkinetic Movements 0 (May 13, 2015). https://doi.org/10.7916/D8T72G9G.

Kametani, Fuyuki, and Masato Hasegawa. "Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease." Frontiers in Neuroscience 12 (January 30, 2018). https://doi.org/10.3389/fnins.2018.00025.

Li, Jing Jing, Georgia Dolios, Rong Wang, and Francesca-Fang Liao. "Soluble Beta-Amyloid Peptides, but Not Insoluble Fibrils, Have Specific Effect on Neuronal MicroRNA Expression." PLoS ONE 9, no. 3 (March 4, 2014). https://doi.org/10.1371/journal.pone.0090770.

Li, Zonghua, Francis Shue, Na Zhao, Mitsuru Shinohara, and Guojun Bu. "APOE2: Protective Mechanism and Therapeutic Implications for Alzheimer's Disease." Molecular Neurodegeneration 15, no. 1 (November 4, 2020): 63. https://doi.org/10.1186/s13024-020-00413-4.

Love, Seth, David Louis, and David W. Ellison. Greenfield's Neuropathology Eighth Edition 2-Volume Set. CRC Press, 2008.

McKay, Erin, and Scott E. Counts. "Multi-Infarct Dementia: A Historical Perspective." Dementia and Geriatric Cognitive Disorders Extra 7, no. 1 (May 4, 2017): 160–71. https://doi.org/10.1159/000470836.

Mendel, Tadeusz Andrzej, Teresa Wierzba-Bobrowicz, Eliza Lewandowska, Tomasz Stępień, and Grażyna Maria Szpak. "The Development of Cerebral Amyloid Angiopathy in Cerebral Vessels. A Review with Illustrations Based upon Own Investigated Post Mortem Cases." Polish Journal of Pathology 64, no. 4 (2013): 260–67. https://doi.org/10.5114/pjp.2013.39334.

"Microtubule Assembly, Organization and Dynamics in Axons and Dendrites | Nature Reviews Neuroscience." Accessed February 17, 2019. https://www.nature.com/articles/nrn2631.

Miki, Tomoko, Osamu Yokota, Hideki Ishizu, Shigetoshi Kuroda, Etsuko Oshima, Seishi Terada, and Norihito Yamada. "Behavioral Variant of Frontotemporal Dementia: Fundamental Clinical Issues Associated with Prediction of Pathological Bases." Neuropathology 36, no. 4 (2016): 388–404. https://doi.org/10.1111/neup.12290.

Pan, K M, M Baldwin, J Nguyen, M Gasset, A Serban, D Groth, I Mehlhorn, Z Huang, R J Fletterick, and F E Cohen. "Conversion of Alpha-Helices into Beta-Sheets Features in the Formation of the Scrapie Prion Proteins." Proceedings of the National Academy of Sciences of the United States of America 90, no. 23 (December 1, 1993): 10962–66.

Perry, David C, Jesse A Brown, Katherine L Possin, Samir Datta, Andrew Trujillo, Anneliese Radke, Anna Karydas, et al. "Clinicopathological Correlations in Behavioural Variant Frontotemporal Dementia." Brain 140, no. 12 (December 1, 2017): 3329–45. https://doi.org/10.1093/brain/awx254.

Rabinovici, Gil D., and Bruce L. Miller. "Frontotemporal Lobar Degeneration." CNS Drugs 24, no. 5 (May 1, 2010): 375–98. https://doi.org/10.2165/11533100-000000000-00000.

Rambaran, Roma N, and Louise C Serpell. "Amyloid Fibrils." Prion 2, no. 3 (2008): 112–17.

Rigamonti, Daniele. Adult Hydrocephalus. Cambridge University Press, 2014.

Rodriguez, Moses, Orhun H. Kantarci, and Istvan Pirko. Multiple Sclerosis. Oxford University Press, 2013.

Saint-Aubert, Laure, Laetitia Lemoine, Konstantinos Chiotis, Antoine Leuzy, Elena Rodriguez-Vieitez, and Agneta Nordberg. "Tau PET Imaging: Present and Future Directions." Molecular Neurodegeneration 12 (February 20, 2017). https://doi.org/10.1186/s13024-017-0162-3.

Schmit, Jeremy D., Kingshuk Ghosh, and Ken Dill. "What Drives Amyloid Molecules To Assemble into Oligomers and Fibrils?" Biophysical Journal 100, no. 2 (January 19, 2011): 450–58. https://doi.org/10.1016/j.bpj.2010.11.041.

Stojanov, Dragan, Aleksandra Aracki-Trenkic, Slobodan Vojinovic, Srdjan Ljubisavljevic, Daniela Benedeto-Stojanov, Aleksandar Tasic, and Sasa Vujnovic. "Imaging Characteristics of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL)." Bosnian Journal of Basic Medical Sciences 15, no. 1 (February 2015): 1–8. https://doi.org/10.17305/bjbms.2015.247.

The Science of Parkinson's. "Are Lewy Bodies Fake News?," December 3, 2017. https://scienceofparkinsons.com/2017/12/03/lewy-2/.

Williams, Michael A., and Jan Malm. "Diagnosis and Treatment of Idiopathic Normal Pressure Hydrocephalus:" CONTINUUM: Lifelong Learning in Neurology 22, no. 2, Dementia (April 2016): 579–99. https://doi.org/10.1212/CON.0000000000000305.

Yamada, Thoru, and Elizabeth Meng. Practical Guide for Clinical Neurophysiologic Testing: EEG. Lippincott Williams & Wilkins, 2012.