**Author details**

in the lymphocytes from AD patients [48]. (3) By contrast, tacrine, AChEI, impaired brain mitochondrial respiratory complex I, IV, and V activities in XX model [49]. Therefore, further studies are required to provide more evidence to support the effects of AChE inhibitor on brain mitochondrial function in AD patients as well as in the metabolic syndrome subjects. Those findings of AChEIs on brain mitochondrial function and their association with the

Abbreviations: AChE, acetylcholinesterase; APP, amyloid beta precursor; AD, Alzheimer's disease; Ca2+, calcium; Aβ,

**Table 7.** The effects of acetylcholine esterase inhibitors (AChEIs), the standard drugs for AD treatment, on brain

**Study model Major findings Refs**

*T maze*

• ↑%Accuracy *Elevated plus maze* • ↑Entry number into open arm • ↑Time in open arm

**Cognitive function AD** 

**marker**

N/A N/A Rivastigmin

N/A • ↓AChE Tacrine


**Interpretation**

[47]

[48]

[49]

Donepezil attenuated brain mitochondrial swelling, reduced brain Aβ accumulation, and improved cognitive function in AD mice.

enhanced mitochondrial electron transport chain function in AD patients.

impaired brain mitochondrial function in rats.

**Mitochondrial parameters**

> mitochondrial swelling

complex I and III • ↑Enzymatic activities of complex II, III and IV • ↔Mitochondrial content

N/A • ↓Ca2+ induced

N/A • ↑Oxidation of

N/A • ↓ Complex I, IV, V activity

mitochondrial function and their association with the development of Alzheimer's disease.

The presence of MetS is associated with an increase in the incidence of pre-AD. The possible underlying mechanisms involved in the association of pre-AD in MetS are still unclear. From this study, we concluded that mitochondrial dysfunction could be an important feature of AD pathogenesis in MetS. In addition, the findings indicate that the intervention which improved brain mitochondrial function led to improved cognitive function. These findings provide

development of Alzheimer's disease are summarized in **Table 7**.

**5. Clinical implications**

**Models/ interventions/ duration**

months

AD patients/ rivastigmin (6–12 mg/ day)/6 months

Wistar rats/tacrine (15

amyloid beta; N/A, not assessed.

mg/kg)/8 h

APP/PS1 (APPswe/ PS1dE9)/Donepezil (1 mg/kg) or vehicle/2

**Metabolic parameters**

72 Alzheimer's Disease - The 21st Century Challenge

Nattayaporn Apaijai1,2, Wasana Pratchayasakul1,2,3, Nipon Chattipakorn1,2,3 and Siriporn C. Chattipakorn1,2,4\*

\*Address all correspondence to: scchattipakorn@gmail.com

1 Neurophysiology Unit, Faculty of Medicine, Cardiac Electrophysiology Research and Training Center, Chiang Mai University, Chiang Mai, Thailand

2 Center of Excellence in Cardiac Electrophysiology Research, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

3 Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

4 Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
